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SPRINGER BRIEFS IN MOLECULAR SCIENCE

Xiaoyu Wang Wenjing Guo Yihui Hu Jiangjiexing Wu Hui Wei

Nanozymes: Next Wave of Artificial Enzymes

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SpringerBriefs in Molecular Science

More information about this series at http://www.springer.com/series/8898

Xiaoyu Wang Wenjing Guo Yihui Hu Jiangjiexing Wu Hui Wei •

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Nanozymes: Next Wave of Artiﬁcial Enzymes

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Xiaoyu Wang Department of Biomedical Engineering, College of Engineering and Applied Sciences, Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing National Laboratory of Microstructures Nanjing University Nanjing China

Jiangjiexing Wu Department of Biomedical Engineering, College of Engineering and Applied Sciences, Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing National Laboratory of Microstructures Nanjing University Nanjing China

Wenjing Guo Department of Biomedical Engineering, College of Engineering and Applied Sciences, Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing National Laboratory of Microstructures Nanjing University Nanjing China

Hui Wei Department of Biomedical Engineering, College of Engineering and Applied Sciences, Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing National Laboratory of Microstructures Nanjing University Nanjing China

Yihui Hu Department of Biomedical Engineering, College of Engineering and Applied Sciences, Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing National Laboratory of Microstructures Nanjing University Nanjing China

ISSN 2191-5407 ISSN 2191-5415 (electronic) SpringerBriefs in Molecular Science ISBN 978-3-662-53066-5 ISBN 978-3-662-53068-9 (eBook) DOI 10.1007/978-3-662-53068-9 Library of Congress Control Number: 2016946947 © The Author(s) 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speciﬁcally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microﬁlms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speciﬁc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer-Verlag GmbH Berlin Heidelberg

Preface

This book is intended to describe the concepts, the up-to-date developments, and the perspectives of the ﬁeld of nanozymes that has been rapidly growing over the past decades. Nanozymes are nanomaterials with enzymatic characteristics. As one of the most exciting ﬁelds, the research of nanozymes lies at the interface of chemistry, biology, materials, and nanotechnology. It is counterintuitive to use nanomaterials to mimic natural enzymes since the two seem to be very different from each other. A careful comparison, however, would reveal that they share many features together. For examples, both of them have nanoscaled sizes, irregular shapes, rich surface chemistry, etc. It is these similarities that enable nanomaterials to imitate natural enzymes. Due to the enormous amounts of literature published in the ﬁeld, it is impossible to provide a comprehensive description of nanozymes here. Instead, it aims to provide a broad picture of nanozymes in the context of artiﬁcial enzyme research. Representative examples are discussed to highlight the nanomaterials with enzyme mimicking activities, their catalytic mechanisms, and their promising applications in various areas, ranging from biosensing and cancer diagnostics to tissue engineering and therapeutics. Chapter 1 describes the brief history of nanozymes research in the course of natural enzymes and artiﬁcial enzymes research. It also compares nanozymes with natural enzymes and artiﬁcial enzymes to highlight their unique characteristics. Chapters 2–5 discuss the different nanomaterials used for mimicking various natural enzymes, from carbon-based (Chap. 2) and metal-based (Chap. 3) nanomaterials to metal oxide-based nanomaterials (Chap. 4) and other nanomaterials (Chap. 5). In each of these chapters, the nanomaterials’ enzyme mimetic activities, the catalytic mechanisms, and the key applications are covered. In Chap. 6, the current challenges and future directions of nanozymes research are summarized, which if achieved will help to fulﬁll the great potentials of nanozymes. The purpose of this book is not only to provide insightful knowledge of nanozymes but also to attract more researchers into the ﬁeld and to inspire them to further broaden the ﬁeld. Due to the importance of nanozymes and professional

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writing with plenty of color illustrations and tables, this book should be an ideal choice for readers from different areas, such as chemistry, materials, nanoscience and nanotechnology, biomedical and clinical studies, environment, green chemistry, novel catalysts, etc. I wish to express my appreciation to all the excellent scholars around the world who have contributed and will continue to contribute to the ﬁelds of nanozymes. I would also like to thank my lab members and my collaborators for their contributions to this exciting ﬁeld. I thank my advisors Profs. Erkang Wang, Xinghua Xia, Yi Lu, and Shuming Nie for their guidance, support, and encouragement. I am much indebted to June Tang for her patience during the writing of this book. I thank Nanjing University, National Natural Science Foundation of China, 973 Program, Natural Science Foundation of Jiangsu Province, Shuangchuang Program of Jiangsu Province, PAPD program, Fundamental Research Funds for Central Universities, Six Talents Summit Program of Jiangsu Province, Open Funds of the State Key Laboratory of Electroanalytical Chemistry, Open Funds of the State Key Laboratory of Analytical Chemistry for Life Science, Open Funds of the State Key Laboratory for Chemo/Biosensing and Chemometrics, and Thousand Talents Program for Young Researchers for providing the academic environment and the ﬁnancial support of our research. Nanjing April 2016

Hui Wei

Contents

1 Introduction to Nanozymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Carbon-Based Nanomaterials for Nanozymes . . . . . . . . . . . . . . . 2.1 Fullerene and Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.1 Fullerene and Derivatives as Nuclease Mimics . . . . . . 2.1.2 Fullerene and Derivatives as SOD Mimics . . . . . . . . . 2.1.3 Fullerene Derivatives as Peroxidase Mimics . . . . . . . . 2.2 Graphene and Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1 Graphene and Its Derivatives as Peroxidase Mimics . . 2.2.2 Decorated Graphene (or Its Derivatives) as Peroxidase Mimics . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Carbon Nanotubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.1 Carbon Nanotubes as Peroxidase Mimics . . . . . . . . . . 2.3.2 Carbon Nanotubes as Other Enzyme Mimics . . . . . . . 2.4 Other Carbon-Based Nanomaterials . . . . . . . . . . . . . . . . . . . . 2.4.1 Other Carbon Nanomaterials as Peroxidase Mimics . . 2.4.2 Other Carbon Nanomaterials as SOD Mimics . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Metal-Based Nanomaterials for Nanozymes . . . . . . . . . . . . . . . . 3.1 Metal Nanomaterials with Catalytic Monolayers (Type I). . . . 3.1.1 AuNPs Protected by Alkanethiol with Catalytic Terminal Moieties . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.2 AuNPs Protected by Alkanethiol with Non-covalently Assembled Catalytic Moieties . . . . . . . . . . . . . . . . . . . 3.1.3 AuNPs Protected by Thiolated Biomolecules . . . . . . .

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3.2 Metal Nanomaterials with Intrinsic Enzyme Mimicking Activities (Type II) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.1 Metal Nanomaterials as GOx Mimics . . . . . . . . . . . . . 3.2.2 Metal Nanomaterials as Multiple Enzyme Mimics . . . 3.2.3 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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4 Metal Oxide-Based Nanomaterials for Nanozymes . . . . . . 4.1 Cerium Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.1 Cerium Oxide as SOD Mimics . . . . . . . . . . . . . 4.1.2 Cerium Oxide as Catalase Mimics . . . . . . . . . . 4.1.3 Cerium Oxide as Peroxidase Mimics . . . . . . . . 4.1.4 Cerium Oxide as Oxidase Mimics . . . . . . . . . . . 4.1.5 Cerium Oxide as Other Mimics . . . . . . . . . . . . 4.2 Iron Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.1 Iron Oxide as Peroxidase Mimics . . . . . . . . . . . 4.2.2 Iron Oxide as Other Enzyme Mimics . . . . . . . . 4.3 Other Metal Oxides . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.1 Vanadium Oxide as Enzyme Mimics . . . . . . . . 4.3.2 Cobalt Oxide as Enzyme Mimics . . . . . . . . . . . 4.3.3 Copper Oxide as Enzyme Mimics . . . . . . . . . . . 4.3.4 MoO3, TiO2, MnO2, RuO2 as Enzyme Mimics . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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5 Other Nanomaterials for Nanozymes . 5.1 Prussian Blue . . . . . . . . . . . . . . . . 5.2 Metal-Organic Frameworks. . . . . . 5.3 Metal Chalcogenides. . . . . . . . . . . 5.4 Metal Hydroxides . . . . . . . . . . . . . 5.5 Miscellaneous . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . .

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6 Challenges and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

Abbreviations

4-AAP ABTS AgNP AuNC AuNP BA BSA CEA CNT Color. DAB DOPA DPD dsDNA E-chem ELISA EPR Fluor. HPNP HRP LDH LOD Meth MNPs NMDA NPs OPD PDDA PLGA PMIDA

4-aminoantipyrine 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Silver nanoparticle Gold nanocluster Gold nanoparticle Benzoic acid Bovine serum albumin Carcinoembryonic antigen Carbon nanotube Colorimetric Diazoaminobenzene Dopamine N,N-diethyl-p-phenylenediamine sulfate Double-stranded DNA Electrochemical Enzyme-linked immunosorbent assay Electron paramagnetic resonance Fluorometric 2-hydroxypropyl-4-nitrophenylphosphate Horseradish peroxidase Layered double hydroxide Limit of detection Methods Magnetic nanoparticles N-methyl-D-aspartate Nanoparticles o-phenylenediamine Poly(diallyldimethylammonium chloride) Poly(D,L-lactic-co-glycolic acid) N-(phosphonomethyl)iminodiacetic acid

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PSA PSS PVDF Ref SBA-15 SOD ssDNA TMB

Abbreviations

Prostate-speciﬁc antigen Poly(styrenesulfonate) Polyvinylidene difluoride References Santa Barbara Amorphous type material Superoxide dismutase Single-stranded DNA 3,3′,5,5′-tetramethylbenzidine

Chapter 1

Introduction to Nanozymes

Abstract Natural enzymes play vital roles in biological reactions in living systems. However, some intrinsic drawbacks, such as ease of denaturation, laborious preparation, high cost, and difﬁculty of recycling, have limited their practical applications. To tackle these problems, intensive efforts have been devoted to developing natural enzymes’ alternatives called “artiﬁcial enzymes.” As an emerging research area of artiﬁcial enzymes, nanozymes, the catalytic nanomaterials with enzyme-like characteristics, have attracted researchers’ enormous attentions. In this chapter, after the brief description of the history of nanozymes research in the course of natural enzymes and artiﬁcial enzymes research, a comparison between nanozymes and natural enzymes as well as artiﬁcial enzymes is made. Such a comparison highlights the unique characteristics of nanozymes, such as their size-(shape-, structure-, composition-)tunable catalytic activities, large surface area for modiﬁcation and bioconjugation, multiple functions besides catalysis, smart response to external stimuli, etc.

Keywords Natural enzymes Artiﬁcial enzymes Nanozymes Enzyme mimics Catalytic nanomaterials Nanobiology Functional nanomaterials Biological catalysts Biomimetic chemistry Nanomaterials with enzyme-like characteristics

Natural enzymes are ubiquitous biocatalysts that play central roles in virtually all the biological reactions in living systems [1]. Since they catalyze the reactions with remarkable efﬁciency and extraordinary speciﬁcity at mild conditions (such as room temperature, ambient pressure, aqueous solutions, etc.), natural enzymes have been extensively explored for various applications beyond living systems. For instance, they have been widely used in biomedicine, clinic, environmental and food industry. On the other hand, natural enzymes are proteins or ribonucleic acids, which inevitably have several intrinsic drawbacks, such as ease of denaturation, laborious preparation, high cost, difﬁculty of recycling, etc. These drawbacks have in turn limited their practical applications.

© The Author(s) 2016 X. Wang et al., Nanozymes: Next Wave of Artiﬁcial Enzymes, SpringerBriefs in Molecular Science, DOI 10.1007/978-3-662-53068-9_1

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Introduction to Nanozymes

Fig. 1.1 A brief timeline for the development of artiﬁcial enzymes (natural enzymes are also listed for comparison). Reprinted from Ref. [2], Copyright 2016, with permission from Royal Society of Chemistry

To tackle these drawbacks, intensive efforts have been devoted to developing natural enzymes’ alternatives called “artiﬁcial enzymes” (or “enzyme mimics”) since 1950s (Fig. 1.1) [3]. Artiﬁcial enzymes aim at “imitating the catalytic processes that occur in living systems,” as deﬁned by Breslow [3]. In their pioneering work, Breslow and others have used cyclodextrins and their derivatives to mimic varieties of enzymes, ranging from thiamine pyrophosphate and pyridoxal phosphate to hydrolytic enzymes and even cytochrome P-450 [3]. Inspired by the success of these studies, researchers have investigated numerous types of materials like metal complexes, polymers, supramolecules, and biomolecules (such as nucleic acids, catalytic antibodies, and proteins) for mimicking various kinds of natural enzymes [3]. For example, synthetic polymers with enzyme-like catalytic activities have been studied by Klotz et al. [4]. To date, enormous progress has been made in the ﬁeld of artiﬁcial enzymes (Fig. 1.1), as evidenced by the publication of numerous excellent reviews and even several monographs on the topic [3, 5–22]. Over the past two decades, along with the remarkable achievements made in the ﬁeld of nanotechnology, varieties of functional nanomaterials have been discovered to possess unexpected enzyme-mimicking catalytic activities (Fig. 1.1). These emerging functional nanomaterials are now collectively termed as “nanozymes”. The term “nanozymes” was coined by Pasquato, Scrimin, and their coworkers in 2004 to describe the gold nanoparticle-based transphosphorylation mimics resulting from the self-assembly of triazacyclonane-functionalized thiols onto the surface of gold nanoparticles [23]. Later, in their comprehensive review published in 2013, Wei and Wang deﬁned “nanozymes” as “nanomaterials with enzyme-like characteristics” [24]. As a new type of promising artiﬁcial enzymes, nanozymes have attracted considerable attentions, particularly in recent years. As shown in Fig. 1.2, since the seminal work on fullerene derivatives-based DNase mimics (i.e., their capability for

1 Introduction to Nanozymes

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Fig. 1.2 Number of published papers on nanozymes by the end of 2015. The data is based on Web of Science (April 2016)

oxidative DNA cleavage) in the early 1990s [26], incredible growth has been witnessed in the ﬁeld of nanozymes by the exponential number of publications. By the end of 2015, more than 740 papers on nanozymes have been published, among which 722 were published after 2007. Recently, a special issue has been devoted to nanozymes [27]. The growing interests in nanozymes can be attributed to their unique characteristics over natural enzymes and even conventional artiﬁcial enzymes. Nanozymes are unique in several aspects, such as their size- (shape-, structure-, composition-)tunable catalytic activities, large surface area for modiﬁcation and bioconjugation, multiple functions besides catalysis, smart response to external stimuli, etc. (Table 1.1) [24]. To date, plenty of nanomaterials have been investigated to mimic diverse natural enzymes, which have already found many interesting applications [2, 24, 25, 28–42]. In the following chapters (Chaps. 2–5), nanozymes are discussed based on the nanomaterials rather than the natural enzymes which they mimic because many nanomaterials have exhibited multiple enzyme-mimicking activities. We do not attempt to cover all the published papers on nanozymes in this book. Instead, for each typical nanomaterial, we mainly focus on its enzyme-mimicking activities, catalytic mechanisms, and the key applications. In the last chapter (Chap. 6), we discuss the current challenges and future prospects that nanozyme research is currently facing to fulﬁll its great potentials.

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Table 1.1 Comparison between nanozymes and othersa,

Introduction to Nanozymes

b

Characteristics Nanozymes

(1) (2) (3) (4) (5) (6) (7)

Low cost Easy for mass production Robustness to harsh environments High stability Long-term storage Tunable activity Size- (shape-, structure-, composition-) dependent properties (8) Multifunction (9) Easy for further modiﬁcation (such as bioconjugation) (10) Smart response to external stimuli (11) Self-assembly Conventional artiﬁcial (1) Low cost enzymes (2) Easy mass production (3) Robustness to harsh environments (4) High stability (5) Long-term storage (6) Tunable activity (7) Established methods for preparation and characterization (8) Uniform size and deﬁned structures of molecular mimics (9) Smaller size (compared with nanozymes) Natural enzymes (1) High catalytic efﬁciency (2) High substrate speciﬁcity (3) High (enantio)selectivity (4) Sophisticated three-dimensional structures (5) Wide range of catalytic reactions (6) Tunable activity (7) Good biocompatibility (8) Rational design via protein engineering and computation a The items in italic font are unique for nanozymes compared with conventional artiﬁcial enzymes b The table was adapted from Ref. [24], Copyright 2013, with permission from Royal Society of Chemistry

References 1. Nelson, D. L., & Cox, M. M. (2008). Lehninger principles of biochemistry (5th ed., pp. 183– 229). New York: W. H. Freeman and Company. 2. Wang, X. Y., Hu, Y. H., & Wei, H. (2016). Nanozymes in bionanotechnology: From sensing to therapeutics and beyond. Inorganic Chemistry Frontiers, 3, 41–60. 3. Breslow, R. (2005). Artiﬁcial enzymes. Weinheim: Wiley-VCH. 4. Klotz, I. M., Royer, G. P., & Scarpa, I. S. (1971). Synthetic derivatives of polyethyleneimine with enzyme-like catalytic activity (synzymes). Proceedings of the National Academy of Sciences of the United States of America, 68, 263–264. 5. Breslow, R. (1995). Biomimetic chemistry and artiﬁcial enzymes: catalysis by design. Accounts of Chemical Research, 28, 146–153. 6. Murakami, Y., Kikuchi, J., Hisaeda, Y., & Hayashida, O. (1996). Artiﬁcial enzymes. Chemical Reviews, 96, 721–758.

References

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7. Breslow, R., & Dong, S. D. (1998). Biomimetic reactions catalyzed by cyclodextrins and their derivatives. Chemical Reviews, 98, 1997–2011. 8. Kirby, A. J., Hollfelder, F. (2009). Fom enzyme models to model enzymes. The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 0WF, UK. 9. Aiba, Y., Sumaoka, J., & Komiyama, M. (2011). Artiﬁcial DNA cutters for DNA manipulation and genome engineering. Chemical Society Reviews, 40, 5657–5668. 10. Wulff, G., & Liu, J. Q. (2012). Design of biomimetic catalysts by molecular imprinting in synthetic polymers: The role of transition state stabilization. Accounts of Chemical Research, 45, 239–247. 11. Salvemini, D., Riley, D. P., & Cuzzocrea, S. (2002). SOD mimetics are coming of age. Nature Reviews Drug Discovery, 1, 367–374. 12. Huang, X., Liu, X. M., Luo, Q. A., Liu, J. Q., & Shen, J. C. (2011). Artiﬁcial selenoenzymes: Designed and redesigned. Chemical Society Reviews, 40, 1171–1184. 13. Bhabak, K. P., & Mugesh, G. (2010). Functional mimics of glutathione peroxidase: Bioinspired synthetic antioxidants. Accounts of Chemical Research, 43, 1408–1419. 14. Friedle, S., Reisner, E., & Lippard, S. J. (2010). Current challenges of modeling diiron enzyme active sites for dioxygen activation by biomimetic synthetic complexes. Chemical Society Reviews, 39, 2768–2779. 15. Darbre, T., & Reymond, J. L. (2006). Peptide dendrimers as artiﬁcial enzymes, receptors, and drug-delivery agents. Accounts of Chemical Research, 39, 925–934. 16. Molenveld, P., Engbersen, J. F. J., & Reinhoudt, D. N. (2000). Dinuclear metallo-phosphodiesterase models: Application of calix[4]arenes as molecular scaffolds. Chemical Society Reviews, 29, 75–86. 17. Feiters, M. C., Rowan, A. E., & Nolte, R. J. M. (2000). From simple to supramolecular cytochrome P450 mimics. Chemical Society Reviews, 29, 375–384. 18. Riley, D. P. (1999). Functional mimics of superoxide dismutase enzymes as therapeutic agents. Chemical Reviews, 99, 2573–2587. 19. Mertes, M. P., & Mertes, K. B. (1990). Polyammonium macrocycles as catalysts for phosphoryl transfer—the evolution of an enzyme mimic. Accounts of Chemical Research, 23, 413–418. 20. Gloaguen, F., & Rauchfuss, T. B. (2009). Small molecule mimics of hydrogenases: Hydrides and redox. Chemical Society Reviews, 38, 100–108. 21. Lu, Y., Yeung, N., Sieracki, N., & Marshall, N. M. (2009). Design of functional metalloproteins. Nature, 460, 855–862. 22. Thomas, C. M., & Ward, T. R. (2005). Artiﬁcial metalloenzymes: Proteins as hosts for enantioselective catalysis. Chemical Society Reviews, 34, 337–346. 23. Manea, F., Houillon, F. B., Pasquato, L., & Scrimin, P. (2004). Nanozymes: Gold-nanoparticle-based transphosphorylation catalysts. Angewandte Chemie-International Edition, 43, 6165–6169. 24. Wei, H., & Wang, E. K. (2013). Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artiﬁcial enzymes. Chemical Society Reviews, 42, 6060–6093. 25. Bitner, B. R., Marcano, D. C., Berlin, J. M., Fabian, R. H., Cherian, L., Culver, J. C., et al. (2012). Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury. ACS Nano, 6, 8007–8014. 26. Tokuyama, H., Yamago, S., Nakamura, E., Shiraki, T., & Sugiura, Y. (1993). Photoinduced biochemical-activity of fullerene carboxylic-acid. Journal of the American Chemical Society, 115, 7918–7919. 27. http://www.mdpi.com/journal/molecules/special_issues/nanozymes. 28. Gao, L.-Z., & Yan, X.-Y. (2013). Discovery and current application of nanozyme. Progress in Biochemistry and Biophysics, 40, 892–902. 29. Pasquato, L., Pengo, P., & Scrimin, P. (2005). Nanozymes: Functional nanoparticle-based catalysts. Supramolecular Chemistry, 17, 163–171. 30. Nakamura, E., & Isobe, H. (2003). Functionalized fullerenes in water. The ﬁrst 10 years of their chemistry, biology, and nanoscience. Accounts of Chemical Research, 36, 807–815.

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31. Prins, L. J. (2015). Emergence of complex chemistry on an organic monolayer. Accounts of Chemical Research, 48, 1920–1928. 32. Xie, J. X., Zhang, X. D., Wang, H., Zheng, H. Z., & Huang, Y. M. (2012). Analytical and environmental applications of nanoparticles as enzyme mimetics. TrAC-Trends in Analytical Chemistry, 39, 114–129. 33. Celardo, I., Pedersen, J. Z., Traversa, E., & Ghibelli, L. (2011). Pharmacological potential of cerium oxide nanoparticles. Nanoscale, 3, 1411–1420. 34. Lin, Y. H., Ren, J. S., & Qu, X. G. (2014). Catalytically active nanomaterials: a promising candidate for artiﬁcial enzymes. Accounts of Chemical Research, 47, 1097–1105. 35. Karakoti, A., Singh, S., Dowding, J. M., Seal, S., & Self, W. T. (2010). Redox-active radical scavenging nanomaterials. Chemical Society Reviews, 39, 4422–4432. 36. Lin, Y. H., Ren, J. S., & Qu, X. G. (2014). Nano-gold as artiﬁcial enzymes: hidden talents. Advanced Materials, 26, 4200–4217. 37. He, W. W., Wamer, W., Xia, Q. S., Yin, J. J., & Fu, P. P. (2014). Enzyme-like activity of nanomaterials. Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews, 32, 186–211. 38. Xu, C., & Qu, X. G. (2014). Cerium oxide nanoparticle: A remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6, e60. 39. Luo, C., Li, Y., & Long, J. (2015). Recent advances in applications of nanoparticles as enzyme mimetics. Scientia Sinica Chimica, 45, 1026–1041. 40. Gao, L. Z., & Yan, X. Y. (2016). Nanozymes: an emerging ﬁeld bridging nanotechnology and biology. Science China Life Sciences, 59, 400–402. 41. Zheng, L., Zhao, J., Niu, X., & Yang, Y. (2015). Nanomaterial-based peroxidase enzyme mimics with applications to colorimetric analysis and electrochemical sensor. Materials Review, 29(115–120), 129. 42. Cheng, H. J., Wang, X. Y., Wei, H. (2016) Encyclopedia of Physical Organic Chemistry (Chapter 16), Wiley-VCH: Weinheim.

Chapter 2

Carbon-Based Nanomaterials for Nanozymes

Abstract Carbon-based nanomaterials, such as fullerene, graphene, carbon nanotubes, and their derivatives, have been extensively studied to mimic various natural enzymes owing to their fascinating catalytic activities. In this chapter, their enzyme mimetic activities (such as nuclease mimics, superoxide dismutase mimics, peroxidase mimics, etc.) are discussed. The catalytic mechanisms are also discussed if they have been elucidated. Representative examples for applications, from biosensing to therapeutics, are covered.

Keywords Nanozymes Artiﬁcial enzymes Enzyme mimics Carbon-based nanomaterials Fullerene and derivatives Graphene and derivatives Carbon nanotubes Peroxidase mimics Superoxide dismutase mimics Nuclease mimics

Carbon-based nanomaterials, such as fullerene, carbon nanotubes (CNTs), graphene, and their derivatives, have found broad applications in many areas. Owing to their interesting catalytic activities, they have been extensively studied to mimic various natural enzymes. In this chapter, we will discuss the nanozymes based on these carbon nanomaterials.

2.1

Fullerene and Derivatives

Fullerene and its derivatives were among the ﬁrst nanomaterials that have been explored for mimicking natural enzymes [1, 2]. In the early 1990s, the light-induced oxidative DNA cleavage with a C60 derivative (i.e., C60-1) was studied, indicating that fullerene could mimic natural nuclease [1]. A few years later, the superoxide dismutase (SOD) mimicking activity of derivatized C60 was investigated, which led to the long-lasting research interests in fullerene-based nanozymes till today. Fullerene and its derivatives have also been used to mimic other enzymes besides nuclease and SOD.

© The Author(s) 2016 X. Wang et al., Nanozymes: Next Wave of Artiﬁcial Enzymes, SpringerBriefs in Molecular Science, DOI 10.1007/978-3-662-53068-9_2

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2 Carbon-Based Nanomaterials for Nanozymes

Fullerene and Derivatives as Nuclease Mimics

Nuclease catalyzes the cleavage of phosphodiester bond between two nucleotides in a nucleic acid. Pristine fullerenes including C60 are not water soluble, which makes them impossible to mimic enzymes in aqueous solution. Therefore, fullerenes have been solubilized by introducing hydrophilic moieties. Nakamura group have made water-soluble C60-1 and studied its photoinduced biochemical activities (Fig. 2.1) [1]. Interestingly, they established that the fullerene carboxylic acid (i.e., C60-1) oxidatively cleaved DNA under light irradiation. Since C60-1 did not bind to the DNA to be cleaved, the cleavage was random. To address this issue, Hélène, Nakamura and coworkers synthesized C60-2, which had a 14-mer DNA sequence

Fig. 2.1 Fullerene derivatives as nuclease mimics. a Light-induced cleavage of DNA with the fullerene derivative C60-1. b Selective cleavage of DNA by forming a triplex with the fullerene DNA conjugate C60-2. Adapted from Ref. [2], Copyright 2003, with permission from American Chemical Society

2.1 Fullerene and Derivatives

9

complementary to the target DNA (Fig. 2.1) [3]. By forming a triplex, the selective cleavage at guanine-rich sites was achieved. There are other ways to make the selective cleavage possible. For instance, by conjugating fullerenes with DNA intercalators (such as acridine), the formed fullerene derivative could enhance DNA cleavage activity compared with the parent fullerene [4]. These early studies have established that water-soluble fullerene derivatives could mimic nuclease.

2.1.2

Fullerene and Derivatives as SOD Mimics

(a) Fullerenes as SOD mimics: in vitro activities and mechanisms Reactive oxygen species (ROS) plays both beneﬁcial and harmful roles in living systems. Superoxide anion, one of ROS, could cause tissue injury and associated inflammation if it were not properly regulated. In nature, SOD has been evolved to catalyze the disputation of superoxide anions into hydrogen peroxide and molecular oxygen and thus protect living systems from the superoxide anion-induced damage. To overcome the limits of natural SOD (such as limited stability and high cost), great efforts have been devoted to developing SOD mimics. The SOD-mimicking activities of fullerenes have been established by the seminal work from Choi and coworkers and have since been extensively studied [5]. Inspired by the early discovery that C60 could act as a radical sponge, Choi et al. studied the neuroprotective activities of two polyhydroxylated C60 (i.e., C60(OH)12 and C60(OH)nOm, n = 18–20, m = 3–7 hemiketal groups) [5, 7]. Surprisingly, both of the two fullerene derivatives could scavenge free radicals and thus reduce excitotoxic and apoptotic death of cultured cortical neurons. Later, they identiﬁed that C60[C(COOH)2]3 with C3 symmetry (C60-C3) was more effective toward neuron protection [8]. Since superoxide anion could be eliminated via either a stoichiometric scavenging mechanism or a SOD-like catalytic mechanism, systematic studies including electron paramagnetic resonance (EPR) were carried out to conﬁrm the SOD-mimicking activity of C60-C3 [6]. The possible stoichiometric scavenging mechanism was ruled out due to the following facts: ﬁrst, no structural modiﬁcations to C60-C3 were observed; second, the production of oxygen and hydrogen peroxide was detected; and the absence of EPR active (paramagnetic) products. By combining the experimental results with computational data, a catalytic mechanism for SOD-like activity of C60-C3 was proposed (Fig. 2.2). The proposed mechanism was supported by other studies using dendritic C60 derivatives and other computational studies [9, 10]. The neuroprotective effects of fullerene-based SOD mimics were also studied using several other cell lines. For instance, methionine-modiﬁed C60 could protect SH-SY5Y neuroblastoma cells from lead ions (Pb2+) induced oxidative damage and thus improved the cell survival [11]. Though water soluble fullerenes are usually required for enzyme-mimicking studies, it has been demonstrated that pristine C60 aqueous suspension was not only

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Fig. 2.2 Derivatized C60 as SOD mimics. a C60-C3 as a SOD mimic for catalytically converting superoxide anion into hydrogen peroxide, water, and hydroxyl. b The proposed catalytic mechanism. Adapted from Ref. [6], Copyright 2004, with permission from Elsevier

biocompatible but also showed protective effects on liver injury [12]. Besides derivatization, fullerenes could also be solubilized by using the similar strategies for hydrophobic drug solubilization. For instance, pristine C60 has been solubilized in olive oil for various applications [13].

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(b) Fullerenes as SOD mimics: in vivo applications To conclusively demonstrate that C60-C3 could work in living system as a SOD mimic, Dugan et al. employed SOD2 knockout mice as an in vivo model to investigate the therapeutic efﬁcacy of C60-C3 (Fig. 2.3) [6]. The SOD2 knockout mice would die in utero or within a few days after birth owing to mitochondria damage by oxidative species. Therefore, they were suitable models to evaluate the in vivo effects of SOD mimics. It showed that the life span of the SOD2 defective mice could be extended by 300 % when C60-C3 was administrated both in utero and postnatally, demonstrating the C60-C3 could be functional alternatives to SOD2 in the studied mice. SOD2 is a manganese SOD localized in the mitochondria. Further immunostaining indeed revealed that C60-C3 was uptaken and localized to mitochondria [6]. These results indicated that fullerenes with SOD-mimicking activities (such as C60-C3) may hold translational promise for treating several diseases in future.

Fig. 2.3 a Treatment of SOD2 knockout mice with C60-C3. b Percentage of Sod2−/− pups born to Sod2+/− parents. Pregnant dams were given C60-C3 in their drinking water starting at Day 14–15 of pregnancy. Control dams received dilute red food coloring. The percentages of Sod2−/− pups, per litter, born to control versus C60-C3-treated dams were, respectively, 6 ± 2 % (controls, 11 L) and 20 % ± 2 (C3, 9 L) (mean ± standard error of mean, with p = 0.03 by t test, and p = 0.04 by the nonparametric Wilcoxon rank sum test; the theoretical expected percentage is 25 %), indicating in utero rescue of some Sod2−/− embryos. c Survival (days) of Sod2−/− pups treated with daily subcutaneous injection of C60-C3 or color-matched food coloring until death. Values are means ± standard error of mean, *p < 0.05 by t test, n = 9, C60-C3 versus n = 7, vehicle. Adapted from Ref. [6], Copyright 2004, with permission from Elsevier

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2 Carbon-Based Nanomaterials for Nanozymes

Fullerene Derivatives as Peroxidase Mimics

A few studies also showed that fullerenes could mimic peroxidase [14, 15]. For instance, the peroxidase-mimicking activity of C60[C(COOH)2]2 was demonstrated by its catalyzed oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) with H2O2 [15].

2.2

Graphene and Derivatives

Peroxidase catalyzes the oxidation of its substrates with H2O2 into oxidized products. The products are usually either colored or fluorescent, which enables peroxidase for a wide range of bioanalytical and biomedical applications. The peroxidase-mimicking activities of nanomaterials were initially studied with Fe3O4 nanoparticles by Yan and coworkers in 2007 [16]. Inspired by Yan’s work, Wang et al. developed a general sensing strategy using Fe3O4 nanoparticles-based peroxidase mimic in 2008 (see detailed discussion in Chap. 4) [17]. Since then, lots of different nanomaterials have been investigated to mimic peroxidase. Among them, graphene and its various derivatives have showed great promise in mimicking peroxidase. Graphene and its derivatives with peroxidase-mimicking activities can be roughly classiﬁed into two types. For the ﬁrst type, the activities are solely from graphene or its derivatives. For the second type, the activities are either from the catalysts assembled onto graphene (or its derivatives) or from the synergistic effects of both the decorated catalysts and graphene (or its derivatives). Note: other enzyme-mimicking activities of graphene and its derivatives still remain to be investigated [18].

2.2.1

Graphene and Its Derivatives as Peroxidase Mimics

The peroxidase-mimicking activities have been studied mainly with graphene derivatives since pure graphene without any modiﬁcations is not water soluble. Qu and coworkers reported the intrinsic peroxidase-mimicking activity of graphene oxide with carboxyl modiﬁcations (GO-COOH) [19]. The activity was ﬁrst demonstrated by the catalytic oxidation of TMB with H2O2 in the presence of GO-COOH (Fig. 2.4). The kinetic studies revealed that GO-COOH had higher afﬁnity toward TMB in comparison with natural peroxidase. Interestingly, the GO-COOH catalyzed reactions proceeded via a ping-pong mechanism, which was the same as that for natural peroxidase. Since they did not detect trace amount of metal catalysts, they attributed the observed catalytic activity to the GO-COOH itself. No mechanism responsible for the catalytic activity was proposed, though it suggested that electron transfer from GC-COOH to H2O2 may be involved. By

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Fig. 2.4 Carboxyl-modiﬁed graphene oxide as peroxidase mimic. a Typical photographs of the reaction solutions incubated at room temperature in pH 5.0 phosphate buffer (from left to right): (1) 50 mM H2O2 and 800 μM TMB, colorless; (2) 40 mg/mL GO-COOH, black; (3) 50 mM H2O2, 800 mM TMB and 40 mg mL/mL GO-COOH, turning blue. b The time-dependent absorbance changes at 652 nm in the absence (black) or presence of different concentrations of GO-COOH in pH 5.0 phosphate buffer at room temperature. Reprinted from Ref. [19], Copyright 2010, with permission from John Wiley and Sons

combining with natural glucose oxidase (GOx), the glucose in diluted blood and fruit juice samples was successfully detected using the GC-COOH-based peroxidase mimic [19]. Graphene derivatives and many other carbon-based nanomaterials have rich oxygenated functional moieties (such as hydroxyl, ketone, carboxyl, epoxide, etc.). These functional moieties may play key roles in their enzyme-mimicking activities. To ﬁgure out the possible functional moieties responsible for the peroxidasemimicking activity of a graphene derivative called graphene quantum dots (GQDs), several reagents were employed to selectively deactivate these functional moieties (Fig. 2.5) [20]. GQDs are small pieces of graphene derivative with fluorescent properties. It has ketone, hydroxyl, and carboxyl groups on the surface. These three groups can selectively react with phenylhydrazine (PH), benzoic anhydride (BA), and 2-bromo-1-phenylethanone (BrPE) respectively (Fig. 2.5). After treatment with PH, BA, BrPE, the peroxidase-mimicking activities of the treated GQDs were studied. As shown in Fig. 2.5b, the activity of PH-treated GQDs was signiﬁcantly inhibited while the activity of BA-treated GQDs was enhanced. The activity of BrPE-treated GQDs remained almost the same as the untreated GQDs. Using a HO∙ speciﬁc fluorescent probe, the formation of HO∙ was conﬁrmed during the catalytic reaction. Further kinetic measurements and theoretical calculation were also carried out. Taking together, these results suggested that ketone groups were the catalytically active sites and the carboxyl groups were the substrate binding sites. The hydroxyl groups, on the other hand, played an inhibitory role. It may be applicable to other carbon nanomaterials-based peroxidase mimics, which also have such oxygenated moieties.

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Fig. 2.5 Deciphering peroxidase-mimicking activity of GQDs. a Reactions involved in selectively deactivating functional moieties on GQDs. b Relative catalytic activities of GQDs treated with different reagents. Adapted from Ref. [20], Copyright 2015, with permission from John Wiley and Sons

Since HO∙ was involved in peroxidase-mimicking activity of GQDs, they have showed antibacterial activity even in the low level of H2O2. Both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria could be inhibited with the GQDs. The in vivo antibacterial efﬁcacy was then evaluated using a mouse injury model, showing that the combination of GQDs with H2O2 exhibited the best therapeutic effects compared with saline, H2O2, and GQDs [21]. The water solubility and stability of GO could be further enhanced by coating with polymers. To this end, chitosan, a cationic polysaccharide, was used to coat GO. The obtained chitosan–GO showed improved stability toward catalytic oxidation of TMB with H2O2. Interestingly, it was found that the peroxidasemimicking activity of the chitosan–GO was regulated by light [22]. Under visible light irradiation, the catalytic activity was turned on. More, the coated chitosan could interact with concanavalin A (Con A) via a multivalent manner, and the interaction would induce the aggregation of chitosan–GO. Such aggregation in turn reduced the activity of the nanozyme. Glucose, however, could compete for the

2.2 Graphene and Derivatives

15

binding sites of chitosan on Con A due to the stronger interaction between glucose and Con A. Therefore, the presence of glucose would disassemble the chitosan– GO/Con A aggregates and thus recover the catalytic activity. Based on this phenomenon, a facile phototriggered method for glucose detection was developed. A linear range of 2.5–5.0 mM for glucose was achieved [22].

2.2.2

Decorated Graphene (or Its Derivatives) as Peroxidase Mimics

The large surface area of graphene and its derivatives provides a good opportunity to decorate them with various functional molecules and nanomaterials. As mentioned above, for such decorated graphene (or its derivatives), the peroxidasemimicking activities could be originated from either the assembled catalyst itself or the catalyst/graphene (or its derivatives) assembles. In their seminal report, Dong and coworkers assembled hemin onto reduced GO (denoted as rGO) to form hemin–rGO complex and studied its peroxidasemimicking activity (Fig. 2.6). The rGO was obtained by reducing GO with hydrazine. Then the hemin–rGO was prepared through the π-π stacking interaction between hemin and rGO. Compared with hemin–rGO, rGO showed almost negligible activity. Therefore, the peroxidase-mimicking activity of the hemin–rGO was mainly attributed to the assembled hemin. As shown in Fig. 2.6, the hemin– rGO-based nanozyme could catalyze the oxidation of TMB, ABTS (2,2′-azinobis (3-ethylbenzothiozoline)-6-sulfonic acid, and OPD (o-phenylenediamine) into the corresponding colored products with H2O2. Kinetic studies revealed that the hemin–rGO catalyzed reaction also followed a ping-pong mechanism [23].

Fig. 2.6 Hemin-decorated rGO as peroxidase mimic. a Schematic illustration of peroxidase-like activity of hemin–rGO. b Hemin–rGO catalyzed oxidation of various peroxidase substrates with H2O2 to the corresponding colored products. Adapted from Ref. [23], Copyright 2011, with permission from American Chemical Society

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It is known that single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) have different afﬁnity toward various nanomaterials [24]. ssDNA binds tightly onto graphene (or its derivatives) while dsDNA binds weakly. Such a difference could be further ampliﬁed by salt-induced aggregation. In the presence of high concentration of salt (such as NaCl), ssDNA protects graphene (or its derivatives) from aggregation while dsDNA cannot. Based on this phenomenon, Dong et al. went on further to develop a label-free colorimetric method for single-nucleotide polymorphisms (SNPs) (Fig. 2.7) [23]. The probe ssDNA could stabilize the hemin–rGO and thus retained its peroxidase-mimicking activity. When the complementary target ssDNA was hybridized with the probe ssDNA, the formed dsDNA could not stabilize the hemin–rGO, which led to signiﬁcant inhibition of its peroxidase-mimicking activity and produced the weakest signal. When a target ssDNA with a single-base mismatch was introduced, the formed duplex could partially protect the hemin–rGO from aggregation and thus retained part of its peroxidase-mimicking activity. This in turn resulted in the signal with medium intensity. As shown in Fig. 2.7, one could easily distinguish the single-base mismatched target DNA from the complementary one even with naked eyes [23]. This sensing strategy could be applicable to functional nucleic acids (such as aptamers) [24, 25]. An aptamer is an ssDNA or ssRNA that can speciﬁcally bind to its target. The binding usually induces a conformational change of the aptamer. Such a conformational change could in principle be sensed with hemin–rGO. For

Fig. 2.7 Hemin-decorated rGO as peroxidase mimic for single-nucleotide polymorphisms. a Protocol for SNPs detection. (a) Probe ssDNA (no precipitation, dark blue), (b) single-base mismatched duplex DNA (small amount of precipitation, blue), and (c) complementary duplex DNA (much precipitation, light blue). b Time-dependent absorbance changes in the presence of different amounts of target ssDNA. c Time-dependent absorbance changes with corresponding supernatant in (a) ssDNA, (b, c, d) single-base mismatched duplex DNA, and (e) complementary duplex DNA. Reprinted from Ref. [23], Copyright 2011, with permission from American Chemical Society

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instance, when an aptamer for acetamiprid (an insecticide) was used to stabilize hemin–rGO, the nanozyme showed high activity. However, the presence of acetamiprid would form the acetamiprid-aptamer complex, which did not protect the hemin–rGO efﬁciently. Therefore, the nanozyme’s activity was signiﬁcantly inhibited due to the aggregation. With this sensing strategy, as low as 40 nM acetamiprid was detected [26]. Other targets of interests can also be detected when the corresponding aptamers are used. The synergistic effects were observed for numerous decorated graphene (or its derivatives) [27–35]. Among GO, rGO, AuNPs, the mixture of rGO and AuNPs, and the gold nanoparticles-decorated rGO (denoted as AuNPs@rGO), AuNPs@rGO exhibited the highest peroxidase-mimicking activity. As shown in Fig. 2.8, the signiﬁcantly enhanced catalytic activity of the AuNPs@rGO was attributed to the synergistic effects. Careful study suggested that the synergistic effects were due to: (a) the strong interaction between Au 5d of AuNPs and C 2p of

Fig. 2.8 AuNPs@rGO with synergistic peroxidase-mimicking activity and its use for DNA sensing. a TEM (transmission electron microscopy) image of AuNPs@rGO. b Peroxidase-mimicking activities of various nanomaterials. c Comparison of fluorescent retention ratio of FAM-labeled probe ssDNA and the corresponding dsDNA after incubated with AuNPs@rGO. d Time-dependent absorbance changes with varying concentrations of target ssDNA. Adapted from Ref. [27], Copyright 2012, with permission from American Chemical Society

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rGO at the interface, which was favorable to H2O2 and HO∙ absorption; and (b) the modiﬁed electronic structure and Fermi level of rGO owing to the above-mentioned interfacing, which in turn resulted in the n-type doping of rGO and accelerated the catalytic reactions [27]. More, by further exploring the different afﬁnities of ssDNA and dsDNA toward the AuNPs@rGO, a general analytical strategy for target DNA was developed (Fig. 2.8). The ssDNA speciﬁc nuclease (such as S1 nuclease) was also successfully detected using the developed method, where the presence of S1 nuclease would cleave the probe ssDNA into small fragments and thus recover the nanozyme’s activity. If an aptamer was used as the probe ssDNA, the corresponding target (such as insulin) could be detected [27]. A hybrid called GSF@AuNPs with peroxidase-mimicking activity was prepared by in situ formation of AuNPs onto sandwich-like mesoporous silica/rGO. The silica/rGO was pre-conjugated with folic acid for tumor cell recognition [29]. The nanozyme was then used for detection of cancer cells with overexpressed folate receptor. For instance, rapid detection of HeLa cells was achieved. More, since HO∙ was generated during the catalysis, the nanozyme was also used to selectively kill cancer cells with the help of either exogenous or endogenous H2O2 [29]. Chen and coworkers prepared PtNPs decorated GO (i.e., PtNPs/GO) and further modiﬁed it with folic acid [36]. Based on the peroxidase-mimicking activity of the folic acid-PtNPs/GO, a colorimetric assay for cancer cells was developed (Fig. 2.9). With the developed assay, as few as 125 cancer cells have been detected by naked eyes. By conjugating the monoclonal antibody for aflatoxin B1 with a peroxidase-mimicking nanozyme, an electrochemical immunoassay for aflatoxin B1 was reported by Tang et al. [32]. The nanozyme had a structure of PtNPs/CoTPP/rGO, in which CoTPP was 5,10,15,20-tetraphenyl-21H,23Hporphine cobalt. Aflatoxin B1 is a highly toxic metabolite secreted by food fungi and its detection still needs rapid methods with high sensitivity and low cost. With

Fig. 2.9 Colorimetric detection of cancer cells with folic acid–PtNPs/GO as a peroxidase mimic. Reprinted from Ref. [36], Copyright 2014, with permission from American Chemical Society

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the developed immunoassay, as low as 5.0 pg/mL of aflatoxin B1 was successfully detected. Besides, the immunoassay has been used for analyzing real samples, such as the naturally contaminated peanut samples, showing good agreement with ELISA (enzyme-linked immunosorbent assay) kit [32]. Yu and coworkers reported a disposable electrochemical immunosensor based on peroxidase-mimicking nanozyme for cancer antigen 153 (CA153) detection [34]. Their nanozyme had a structure of ZnFe2O4@silica/GO (Fig. 2.10). The antibodies were conjugated onto the silica shell. Using a sandwich assay format, sensitive and selective detection of CA153 was achieved with a dynamic range from 10−3 to 200 U/mL and a detection limit of 2.8 × 10−4 U/mL. The fabricated immunosensor was further used to detect CA153 in serum samples and the results were consistent with the clinical ones.

Fig. 2.10 Peroxidase-mimicking nanozyme and its use for disposable electrochemical immunosensor. Reprinted from Ref. [34], Copyright 2014, with permission from Elsevier

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2 Carbon-Based Nanomaterials for Nanozymes

Carbon Nanotubes

CNTs as well as decorated CNTs have been used to mainly mimic peroxidase though other CNT-based enzyme mimics were also reported [37, 38].

2.3.1

Carbon Nanotubes as Peroxidase Mimics

Qu and coworkers reported the peroxidase-mimicking activity of single-walled carbon nanotubes (SWNTs) [39]. The activity of SWNTs was investigated by catalytic oxidation of TMB with H2O2. Since metal catalysts are usually used to grow SWNTs, a trace amount of metal catalyst residues rather than SWNTs themselves may be responsible for the mimicking activity. To address this concern, the sonication-assisted washing with mixed acids (i.e., a mixture of concentrated sulfuric and nitric acids) was carried out to completely remove the metal residues (i.e., Co). It was found that pristine SWNTs and treated SWNTs did not show any signiﬁcant differences in their catalytic activities. This conﬁrmed that the peroxidase-mimicking activity of SWNTs was from the SWNTs themselves instead of the metal residues. By exploring the different afﬁnities of ssDNA and dsDNA toward SWNTs, they developed a colorimetric assay for DNA detection [39]. It should be noted that in the above study, only the effect of Co on SWNTs’ peroxidase-mimicking activity was tested. Other metal residues may have different effects. Zhu and coworkers indeed found that Fe content in the helical CNTs played an important role in their catalytic activities [40]. As shown in Fig. 2.11, the more Fe content of helical CNT was, the higher its peroxidase-mimicking activity of helical CNT was. Even for the helical CNT with the lowest amount of Fe, its activity was still higher than that of MWNTs (multiwalled CNTs). Zhu’s and Qu’s results suggest that more systematic studies are needed to decipher the exact mechanisms of CNTs’ enzyme-mimicking activities. Zhu et al. then fabricated an electrochemical sensor using the helical CNTs as peroxidase mimic for H2O2 detection [40]. Like graphene, the decoration of CNTs could also synergistically enhance their peroxidase-mimicking activities. When MWNTs were decorated with magnetic silica nanoparticles, the decorated MWNTs exhibited higher peroxidase-mimicking activity compared with the individual components (i.e., MWNTs and magnetic silica nanoparticles, respectively) [41]. Since the decoration of magnetic silica nanoparticles onto MWNTs was achieved by the Cu2+-mediated click chemistry, a colorimetric assay for Cu2+ was proposed (Fig. 2.12). The decorated MWNTs could be concentrated by a magnet and then used to oxidize TMB to its colored products. On the other hand, the undecorated MWNTs would be washed away and only the magnetic silica nanoparticles would be concentrated by a magnet. The latter exhibited much lower catalytic activity compared with the decorated

2.3 Carbon Nanotubes

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Fig. 2.11 Peroxidase-mimicking activity of helical CNTs. a SEM (scanning electron microscopy) image of helical CNTs. b Peroxidase-mimicking activities of helical CNTs with different Fe contents as well as MWNTs. The catalytic reaction without CNTs was shown as a control. Adapted from Ref. [40], Copyright 2011, with permission from John Wiley and Sons

MWNTs. Via such a sensing strategy, high sensitive and selective detection of Cu2+ has been carried out [41]. Other decorated CNTs with synergistically enhanced peroxidase-mimicking activities have also been developed and used to detect biologically important targets

Fig. 2.12 Cu2+ detection using magnetic silica nanoparticles clicked on MWNTs. a The sensing mechanism. b The time-dependent absorbance changes in the absence (black) or presence of different concentration of Cu2+. c Calibration curve for variable concentrations of Cu2+. The error bars represent the standard deviation of three measurements. Reprinted from Ref. [41], Copyright 2010, with permission from Royal Society of Chemistry

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(also see Tables A1 and A2). For example, when MWNTs were ﬁlled with Prussian blue nanoparticles, the formed nanozyme has been used for colorimetric detection of H2O2 [42]. When the nanozyme was further combined with glucose oxidase, it has been successfully used for glucose detection with a linear range of 1 μM to 1.0 mM and a detection limit of 200 nM. The potential practical application was demonstrated by detecting glucose in serum samples, showing satisfactory recoveries of 94–106 % [42]. Cholesterol levels in milk powder were evaluated by using ZnO nanoparticles-decorated CNTs as a peroxidase mimic [43]. Cholesterol was catalytically oxidized with cholesterol oxidase to produce H2O2, which was then used for oxidizing ABTS into the colored product with the nanozyme. A colorimetric approach to detection of D-alanine was developed by using Au nanoparticles-decorated SWNTs as a peroxidase mimic [44]. D-alanine was catalytically oxidized with D-amino acids oxidase to produce H2O2 for the further oxidation of TMB. The proposed approach showed high selectivity and high sensitivity toward D-alanine detection. A paper-based immunoassay was developed using ZnFe2O4-decorated MWNTs as a peroxidase mimic [45]. Carcinoembryonic antigen (CEA) was chosen due to its correlation with cancer. The nanozymes-based immunoassay exhibited high sensitivity and robustness. More, the immunoassay has been used to detect CEA in clinical serum samples, showing consistent results compared with a commercialized ELISA method [45].

2.3.2

Carbon Nanotubes as Other Enzyme Mimics

As discussed above, it has been established that fullerenes can efﬁciently scavenge radicals due to their SOD-mimicking activities. Thus, it is reasonable to investigate the radical scavenging activities of CNTs. Tour and coworkers have studied the radical scavenging activities of several SWNTs (Fig. 2.13) [37]. They used butylated hydroxytoluene (BHT), a phenolic antioxidant, to modify the SWNTs. The anchored BHT would endow the SWNTs with radical scavenging activities. Pristine SWNT (SWNT-1) was not water soluble. Therefore, it was solubilized by either wrapping a polymer (such as Pluronic for SWNT-2) or introducing carboxyl moieties by mixed acid treatment/cleavage (i.e., SWNT-3). SWNT-3 was further modiﬁed with PEG (poly(ethylene glycol)) to produce SWNT-4, which was soluble in buffer. The radical scavenging activities were evaluated by comparing with Trolox, a vitamin E derivate. The TME (Trolox mass equivalence) values were then determined. Unexpectedly, SWNT-4 without BHT modiﬁcation exhibited nearly 40 times higher activity (Fig. 2.14). This indicated that SWNTs alone could act as antioxidants. For SWNT-5, amine-BHT was assembled via electrostatic interactions while amine-BHT was covalently conjugated for SWNT-6. Since electrostatic binding was more efﬁcient than the covalent binding, more amine-BHT should bind onto SWNT-5 than SWNT-6. As expected, SWNT-5 showed higher radical scavenging activity than SWNT-6 did (Fig. 2.14). For SWNT-2 and SWNT-7, one

2.3 Carbon Nanotubes

23

Fig. 2.13 SWNTs used for scavenging radicals. Adapted from Ref. [37], Copyright 2009, with permission from American Chemical Society

would expect that SWNT-7 would have higher activity since it had extra BHT moieties. Surprisingly, SWNT-7 exhibited lower activity when compared with SWNT-2 (Fig. 2.14) [37]. This unexpected result indicated that pristine SWNTs had higher radical scavenging activities than BHT. This study demonstrated that SWNTs could act as potent antioxidant without acute cellular toxicity.

Fig. 2.14 Radical scavenging activities (i.e., the TME values) of the SWNTs studied. C60-5 was also included for a comparison. Adapted from Ref. [37], Copyright 2009, with permission from American Chemical Society

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Note that though it has established that fullerenes act as SOD mimic to scavenge radicals, whether CNTs share a similar SOD mimetic mechanism still remains to be investigated.

2.4

Other Carbon-Based Nanomaterials

Other carbon-based nanomaterials (such as carbon nanohorn, carbon nanodots, carbon nanoclusters, etc.) have also been used to mimic peroxidase and other enzymes [46–58].

2.4.1

Other Carbon Nanomaterials as Peroxidase Mimics

Several groups studied the peroxidase-mimicking activities of carbon nanohorns, carbon nanodots, etc. [46–48, 50–52, 58, 59] For instance, Xu and coworkers demonstrated that carboxyl-functionalized single-walled carbon nanohorns exhibited peroxidase-like activity (Fig. 2.15) [46]. When the nanozyme was further combined with glucose oxidase, a facile colorimetric assay for glucose was developed. Carbon nanodots with an average size of 2.5 nm also showed peroxidase-mimicking activity and have been used for glucose sensing (Fig. 2.15c) [51]. The peroxidase-like activity of selenium-doped graphitic carbon nitride nanosheets was demonstrated and further explored for xanthine detection when facilitated with xanthine oxidase [52]. Using [Cu3(BTC)2] (BTC = 1,3,5-benzene tricarboxylate) as a precursor, copper nanoparticles-decorated carbon nanocomposite was fabricated via a one-pot thermolysis method (Fig. 2.15d) [47]. It demonstrated that the nanocomposite exhibited peroxidase mimetic activity. Ascorbic acid, a biologically important antioxidant, could competitively inhibit the catalytic oxidation of peroxidase substrate (such as TMB in this study). Based on this inhibition phenomenon, a colorimetric method for ascorbic acid was developed [47, 60]. The ascorbic acid content in tablets has been successfully determined with the nanozyme-based method [47].

2.4.2

Other Carbon Nanomaterials as SOD Mimics

The SOD-mimicking activities of nitrogen-doped carbon nanodots have been studied [58]. It demonstrated that primary amine were the optimal reagents for nitrogen doping. When the obtained nitrogen-doped carbon nanodots were added to H2O2-treated cells, they would enhance the cell viability in a concentrationdependent manner. It suggested that the nitrogen-doped carbon nanotdots protect cells from H2O2-induced injury by eliminating the ROS and stimulating the native SOD expression [58].

References

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Fig. 2.15 Carbon nanomaterials as peroxidase mimics. a Single-walled carbon nanohorns as peroxidase mimic and b their use for glucose detection. c Carbon nanodots as peroxidase mimics. d Copper nanoparticles-decorated carbon as peroxidase mimics. a and b Reprinted from Ref. [46], Copyright 2015, with permission from Royal Society of Chemistry. c Reprinted from Ref. [51], Copyright 2011, with permission from Royal Society of Chemistry. d Reprinted from Ref. [47], Copyright 2014, with permission from John Wiley and Sons

References 1. Tokuyama, H., Yamago, S., Nakamura, E., Shiraki, T., & Sugiura, Y. (1993). Photoinduced biochemical-activity of fullerene carboxylic-acid. Journal of the American Chemical Society, 115, 7918–7919. 2. Nakamura, E., & Isobe, H. (2003). Functionalized fullerenes in water. The ﬁrst 10 years of their chemistry, biology, and nanoscience. Accounts of Chemical Research, 36, 807–815. 3. Boutorine, A. S., Tokuyama, H., Takasugi, M., Isobe, H., Nakamura, E., & Helene, C. (1994). Fullerene-oligonucleotide conjugates: Photoinduced sequence-speciﬁc DNA cleavage. Angewandte Chemie-International Edition, 33, 2462–2465. 4. Yamakoshi, Y. N., Yagami, T., Sueyoshi, S., & Miyata, N. (1996). Acridine adduct of 60 fullerene with enhanced DNA-cleaving activity. Journal of Organic Chemistry, 61, 7236–7237. 5. Dugan, L. L., Gabrielsen, J. K., Yu, S. P., Lin, T. S., & Choi, D. W. (1996). Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. Neurobiology of Disease, 3, 129–135. 6. Ali, S. S., Hardt, J. I., Quick, K. L., Kim-Han, J. S., Erlanger, B. F., Huang, T. T., et al. (2004). A biologically effective fullerene (C-60) derivative with superoxide dismutase mimetic properties. Free Radical Biology and Medicine, 37, 1191–1202.

26

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7. Krusic, P. J., Wasserman, E., Keizer, P. N., Morton, J. R., & Preston, K. F. (1991). Radical reactions of C60. Science, 254, 1183–1185. 8. Dugan, L. L., Turetsky, D. M., Du, C., Lobner, D., Wheeler, M., Almli, C. R., et al. (1997). Carboxyfullerenes as neuroprotective agents. Proceedings of the National Academy of Sciences of the United States of America, 94, 9434–9439. 9. Liu, G.-F., Filipovic, M., Ivanovic-Burmazovic, I., Beuerle, F., Witte, P., & Hirsch, A. (2008). High catalytic activity of dendritic C60 monoadducts in metal-free superoxide dismutation. Angewandte Chemie-International Edition, 47, 3991–3994. 10. Osuna, S., Swart, M., & Sola, M. (2010). On the mechanism of action of fullerene derivatives in superoxide dismutation. Chemistry-A European Journal, 16, 3207–3214. 11. Chen, T., Li, Y.-Y., Zhang, J.-L., Xu, B., Lin, Y., Wang, C.-X., et al. (2011). Protective effect of C60-methionine derivate on lead-exposed human SH-SY5Y neuroblastoma cells. Journal of Applied Toxicology, 31, 255–261. 12. Gharbi, N., Pressac, M., Hadchouel, M., Szwarc, H., Wilson, S. R., & Moussa, F. (2005). 60 Fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Letters, 5, 2578–2585. 13. Baati, T., Bourasset, F., Gharbi, N., Njim, L., Abderrabba, M., Kerkeni, A., et al. (2012). The prolongation of the lifespan of rats by repeated oral administration of 60 fullerene. Biomaterials, 33, 4936–4946. 14. Okuda, K., Mashino, T., & Hirobe, M. (1996). Superoxide radical quenching and cytochrome c peroxidase-like activity of C60-dimalonic acid, C62(COOH)4. Bioorganic & Medicinal Chemistry Letters, 6, 539–542. 15. Li, R. M., Zhen, M. M., Guan, M. R., Chen, D. Q., Zhang, G. Q., Ge, J. C., et al. (2013). A novel glucose colorimetric sensor based on intrinsic peroxidase-like activity of C60carboxyfullerenes. Biosensors & Bioelectronics, 47, 502–507. 16. Gao, L. Z., Zhuang, J., Nie, L., Zhang, J. B., Zhang, Y., Gu, N., et al. (2007). Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nature Nanotechnology, 2, 577–583. 17. Wei, H., & Wang, E. (2008). Fe3O4 magnetic nanoparticles as peroxidase mimetics and their applications in H2O2 and glucose detection. Analytical Chemistry, 80, 2250–2254. 18. Liu, T., Niu, X., Shi, L., Zhu, X., Zhao, H., & Lana, M. (2015). Electrocatalytic analysis of superoxide anion radical using nitrogen-doped graphene supported Prussian Blue as a biomimetic superoxide dismutase. Electrochimica Acta, 176, 1280–1287. 19. Song, Y., Qu, K., Zhao, C., Ren, J., & Qu, X. (2010). Graphene oxide: Intrinsic peroxidase catalytic activity and its application to glucose detection. Advanced Materials, 22, 2206–2210. 20. Sun, H. J., Zhao, A. D., Gao, N., Li, K., Ren, J. S., & Qu, X. G. (2015). Deciphering a nanocarbon-based artiﬁcial peroxidase: Chemical identiﬁcation of the catalytically active and substrate-binding sites on graphene quantum dots. Angewandte Chemie-International Edition, 54, 7176–7180. 21. Sun, H., Gao, N., Dong, K., Ren, J., & Qu, X. (2014). Graphene quantum dots-band-aids used for wound disinfection. ACS Nano, 8, 6202–6210. 22. Wang, G. L., Xu, X. F., Wu, X. M., Cao, G. X., Dong, Y. M., & Li, Z. J. (2014). Visible-light-stimulated enzymelike activity of graphene oxide and its application for facile glucose sensing. Journal of Physical Chemistry C, 118, 28109–28117. 23. Guo, Y. J., Deng, L., Li, J., Guo, S. J., Wang, E. K., & Dong, S. J. (2011). Hemin-graphene hybrid nanosheets with intrinsic peroxidase-like activity for label-free colorimetric detection of single-nucleotide polymorphism. ACS Nano, 5, 1282–1290. 24. Wei, H., Li, B. L., Li, J., Wang, E. K., Dong, S. J. (2007) Simple and sensitive aptamer-based colorimetric sensing of protein using unmodiﬁed gold nanoparticle probes. Chemical Communications, 3735–3737. 25. Wei, H., Li, B. L., Li, J., Dong, S. J., & Wang, E. K. (2008). DNAzyme-based colorimetric sensing of lead (Pb2+) using unmodiﬁed gold nanoparticle probes. Nanotechnology, 19, 095501.

References

27

26. Yang, Z., Qian, J., Yang, X., Jiang, D., Du, X., Wang, K., et al. (2015). A facile label-free colorimetric aptasensor for acetamiprid based on the peroxidase-like activity of hemin-functionalized reduced graphene oxide. Biosensors & Bioelectronics, 65, 39–46. 27. Liu, M., Zhao, H. M., Chen, S., Yu, H. T., & Quan, X. (2012). Interface engineering catalytic graphene for smart colorimetric biosensing. ACS Nano, 6, 3142–3151. 28. Liu, M., Zhao, H. M., Chen, S., Yu, H. T., & Quan, X. (2012). Stimuli-responsive peroxidase mimicking at a smart graphene interface. Chemical Communications, 48, 7055–7057. 29. Maji, S. K., Mandal, A. K., Nguyen, K. T., Borah, P., & Zhao, Y. L. (2015). Cancer cell detection and therapeutics using peroxidase-active nanohybrid of gold nanoparticle-loaded mesoporous silica-coated graphene. ACS Applied Materials & Interfaces, 7, 9807–9816. 30. Wang, H., Li, S., Si, Y. M., Sun, Z. Z., Li, S. Y., & Lin, Y. H. (2014). Recyclable enzyme mimic of cubic Fe3O4 nanoparticles loaded on graphene oxide-dispersed carbon nanotubes with enhanced peroxidase-like catalysis and electrocatalysis. Journal of Materials Chemistry B, 2, 4442–4448. 31. Dutta, S., Ray, C., Mallick, S., Sarkar, S., Sahoo, R., Negishi, Y., et al. (2015). A gel-based approach to design hierarchical cus decorated reduced graphene oxide nanosheets for enhanced peroxidase-like activity leading to colorimetric detection of dopamine. Journal of Physical Chemistry C, 119, 23790–23800. 32. Shu, J., Qiu, Z., Wei, Q., Zhuang, J., & Tang, D. (2015). Cobalt-porphyrinplatinum-functionalized reduced graphene oxide hybrid nanostructures: A novel peroxidase mimetic system for improved electrochemical immunoassay. Scientiﬁc Reports, 5, 15113. 33. Ma, Z., Qiu, Y. F., Yang, H. H., Huang, Y. M., Liu, J. J., Lu, Y., et al. (2015). Effective synergistic effect of dipeptide-polyoxometalate-graphene oxide ternary hybrid materials on peroxidase-like mimics with enhanced performance. ACS Applied Materials & Interfaces, 7, 22036–22045. 34. Ge, S., Sun, M., Liu, W., Li, S., Wang, X., Chu, C., et al. (2014). Disposable electrochemical immunosensor based on peroxidase-like magnetic silica-graphene oxide composites for detection of cancer antigen 153. Sensors and Actuators B-Chemical, 192, 317–326. 35. Yan, X., Gu, Y., Li, C., Tang, L., Zheng, B., Li, Y., et al. (2016). Synergetic catalysis based on the proline tailed metalloporphyrin with graphene sheet as efﬁcient mimetic enzyme for ultrasensitive electrochemical detection of dopamine. Biosensors & Bioelectronics, 77, 1032–1038. 36. Zhang, L. N., Deng, H. H., Lin, F. L., Xu, X. W., Weng, S. H., Liu, A. L., et al. (2014). In situ growth of porous platinum nanoparticles on graphene oxide for colorimetric detection of cancer cells. Analytical Chemistry, 86, 2711–2718. 37. Lucente-Schultz, R. M., Moore, V. C., Leonard, A. D., Price, B. K., Kosynkin, D. V., Lu, M., et al. (2009). Antioxidant single-walled carbon nanotubes. Journal of the American Chemical Society, 131, 3934–3941. 38. Zhang, B., He, Y., Liu, B., & Tang, D. (2014). NiCoBP-doped carbon nanotube hybrid: A novel oxidase mimetic system for highly efﬁcient electrochemical immunoassay. Analytica Chimica Acta, 851, 49–56. 39. Song, Y., Wang, X., Zhao, C., Qu, K., Ren, J., & Qu, X. (2010). Label-free colorimetric detection of single nucleotide polymorphism by using single-walled carbon nanotube intrinsic peroxidase-like activity. Chemistry-A European Journal, 16, 3617–3621. 40. Cui, R., Han, Z., & Zhu, J.-J. (2011). Helical carbon nanotubes: Intrinsic peroxidase catalytic activity and its application for biocatalysis and biosensing. Chemistry-A European Journal, 17, 9377–9384. 41. Song, Y., Qu, K., Xu, C., Ren, J., & Qu, X. (2010). Visual and quantitative detection of copper ions using magnetic silica nanoparticles clicked on multiwalled carbon nanotubes. Chemical Communications, 46, 6572–6574.

28

2 Carbon-Based Nanomaterials for Nanozymes

42. Wang, T., Fu, Y. C., Chai, L. Y., Chao, L., Bu, L. J., Meng, Y., et al. (2014). Filling carbon nanotubes with prussian blue nanoparticles of high peroxidase- like catalytic activity for colorimetric chemo and biosensing. Chemistry-A European Journal, 20, 2623–2630. 43. Hayat, A., Haider, W., Raza, Y., & Marty, J. L. (2015). Colorimetric cholesterol sensor based on peroxidase like activity of zinc oxide nanoparticles incorporated carbon nanotubes. Talanta, 143, 157–161. 44. Haider, W., Hayat, A., Raza, Y., Chaudhry, A. A., Ihtesham Ur, R., & Marty, J. L. (2015). Gold nanoparticle decorated single walled carbon nanotube nanocomposite with synergistic peroxidase like activity for D-alanine detection. RSC Advances, 5, 24853–24858. 45. Liu, W. Y., Yang, H. M., Ding, Y. A., Ge, S. G., Yu, J. H., Yan, M., et al. (2014). Paper-based colorimetric immunosensor for visual detection of carcinoembryonic antigen based on the high peroxidase-like catalytic performance of ZnFe2O4-multiwalled carbon nanotubes. Analyst, 139, 251–258. 46. Zhu, S. Y., Zhao, X. E., You, J. M., Xu, G. B., & Wang, H. (2015). Carboxylic-group-functionalized single-walled carbon nanohorns as peroxidase mimetics and their application to glucose detection. Analyst, 140, 6398–6403. 47. Tan, H. L., Ma, C. J., Gao, L., Li, Q., Song, Y. H., Xu, F. G., et al. (2014). Metal-organic framework-derived copper nanoparticle@carbon nanocomposites as peroxidase mimics for colorimetric sensing of ascorbic acid. Chemistry-a European Journal, 20, 16377–16383. 48. Liu, S., Tian, J. Q., Wang, L., Luo, Y. L., & Sun, X. P. (2012). A general strategy for the production of photoluminescent carbon nitride dots from organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H2O2 and glucose. RSC Advances, 2, 411–413. 49. Wang, X. H., Qu, K. G., Xu, B. L., Ren, J. S., & Qu, X. G. (2011). Multicolor luminescent carbon nanoparticles: Synthesis, supramolecular assembly with porphyrin, intrinsic peroxidase-like catalytic activity and applications. Nano Research, 4, 908–920. 50. Dong, Y. M., Zhang, J. J., Jiang, P. P., Wang, G. L., Wu, X. M., Zhao, H., et al. (2015). Superior peroxidase mimetic activity of carbon dots-Pt nanocomposites relies on synergistic effects. New Journal of Chemistry, 39, 4141–4146. 51. Shi, W. B., Wang, Q. L., Long, Y. J., Cheng, Z. L., Chen, S. H., Zheng, H. Z., et al. (2011). Carbon nanodots as peroxidase mimetics and their applications to glucose detection. Chemical Communications, 47, 6695–6697. 52. Qian, F. M., Wang, J. M., Ai, S. Y., & Li, L. F. (2015). As a new peroxidase mimetics: The synthesis of selenium doped graphitic carbon nitride nanosheets and applications on colorimetric detection of H2O2 and xanthine. Sensors and Actuators B-Chemical, 216, 418–427. 53. Samuel, E. L. G., Marcano, D. C., Berka, V., Bitner, B. R., Wu, G., Potter, A., et al. (2015). Highly efﬁcient conversion of superoxide to oxygen using hydrophilic carbon clusters. Proceedings of the National Academy of Sciences of the United States of America, 112, 2343–2348. 54. Bitner, B. R., Marcano, D. C., Berlin, J. M., Fabian, R. H., Cherian, L., Culver, J. C., et al. (2012). Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury. ACS Nano, 6, 8007–8014. 55. Marcano, D. C., Bitner, B. R., Berlin, J. M., Jarjour, J., Lee, J. M., Jacob, A., et al. (2013). Design of poly(ethylene glycol)-functionalized hydrophilic carbon clusters for targeted therapy of cerebrovascular dysfunction in mild traumatic brain injury. Journal of Neurotrauma, 30, 789–796. 56. Samuel, E. L. G., Duong, M. T., Bitner, B. R., Marcano, D. C., Tour, J. M., & Kent, T. A. (2014). Hydrophilic carbon clusters as therapeutic, high-capacity antioxidants. Trends in Biotechnology, 32, 501–505. 57. Nilewski, L. G., Sikkema, W. K. A., Kent, T. A., & Tour, J. M. (2015). Carbon nanoparticles and oxidative stress: Could an injection stop brain damage in minutes? Nanomedicine, 10, 1677–1679.

References

29

58. Xu, Z.-Q., Lan, J.-Y., Jin, J.-C., Dong, P., Jiang, F.-L., & Liu, Y. (2015). Highly photoluminescent nitrogen-doped carbon nanodots and their protective effects against oxidative stress on cells. ACS Applied Materials & Interfaces, 7, 28346–28352. 59. Clark, A., Zhu, A. P., Sun, K., & Petty, H. R. (2011). Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis. Journal of Nanoparticle Research, 13, 5547–5555. 60. Cheng, H., Wang, X., & Wei, H. (2015). Ratiometric electrochemical sensor for effective and reliable detection of ascorbic acid in living brains. Analytical Chemistry, 87, 8889–8895.

Chapter 3

Metal-Based Nanomaterials for Nanozymes

Abstract The use of metal nanomaterials for mimicking natural enzymes is discussed in this chapter. These nanozymes are roughly classiﬁed into two types: for type I, the nanozymes’ activities are entirely from the assembled monolayer onto a metallic core rather than the core itself; for type II, the nanozymes’ activities are originated from the metal nanomaterials themselves. For both of them, their enzyme mimetic activities (such as RNase mimics, DNase mimics, superoxide dismutase mimics, peroxidase mimics, catalase mimics, etc.) are discussed. The catalytic mechanisms for the multiple enzyme mimicking activities of metal nanomaterials are elucidated by combing computational studies with experimental results. Representative examples for applications, from biosensing and immunoassays to bioimaging and therapeutics, are covered.

Keywords Nanozymes Artiﬁcial enzymes Enzyme mimics Metal nanomaterials Multiple enzyme mimics Catalytic monolayer-protected gold nanoparticles Immunoassays Self-assembly Computational study Bioanalysis

The metal-based nanozymes could be roughly classiﬁed into two types: for type I, the nanozymes’ activities are entirely from the assembled monolayer onto a metallic core rather than the core itself; for type II, the nanozymes’ activities are originated from the metal nanomaterials themselves. In this chapter, both of them are discussed to highlight their various enzyme mimicking activities and wide applications.

3.1

Metal Nanomaterials with Catalytic Monolayers (Type I)

Metal nanomaterials (such as Au, Ag, etc.) with self-assembled monolayers (particularly the thiolated monolayers) have been extensively explored due to their great importance to nanotechnology [1]. If catalytic moieties were introduced into the © The Author(s) 2016 X. Wang et al., Nanozymes: Next Wave of Artiﬁcial Enzymes, SpringerBriefs in Molecular Science, DOI 10.1007/978-3-662-53068-9_3

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monolayers, one would expect the metal nanomaterials protected by the monolayers to be catalytically active. These functionalized metal nanoparticles could indeed exert enzyme-like catalysis, and therefore, they have been regarded as nanozymes [2–5]. These nanozymes could be further classiﬁed into three subtypes according to the molecules used for the monolayers: the ﬁrst one uses alkanethiol terminated with catalytic moieties; the second one uses alkanethiol without catalytic terminus, and the catalytic moieties, instead, are further assembled onto (or into) the monolayers; and the third one uses thiolated catalytic biomolecules (such as thiolated DNAzymes).

3.1.1

AuNPs Protected by Alkanethiol with Catalytic Terminal Moieties

(a) Alkanethiol-protected AuNPs as RNase mimics: activities and mechanisms As mentioned in Chap. 1, in their initial study, Scrimin and co-workers used alkanethiol terminated with catalytic moieties to modify the AuNP core (Fig. 3.1). The obtained AuNPs assemblies were then used as a metallonuclease (i.e., RNase) mimic to catalyze the transphosphorylation of 2-hydroxypropyl p-nitrophenyl phosphate (HPNPP) [2].

Fig. 3.1 Alkanethiol-protected AuNPs as metallonuclease mimics. a Transphosphorylation catalyzed by RNase A. b Structure of AuNP-1 nanozyme. c Transphosphorylation of HPNPP catalyzed by AuNP-1 nanozyme. c Adapted from Ref. [2], Copyright 2004, with permission from John Wiley and Sons

3.1 Metal Nanomaterials with Catalytic Monolayers (Type I)

33

As shown in Fig. 3.2, in comparison with the uncatalyzed transphosphorylation of HPNPP, the reaction has been accelerated by more than 4 orders of magnitude when AuNP-1 nanozyme was used. More, even compared with the unassembled catalytic molecule Zn-1 (i.e., the complex of 1,4,7-triazacyclononane (TACN) and zinc ion), AuNP-1 nanozyme exhibited more than 600 times rate acceleration. It should note that the AuNP-1 nanozyme catalyzed reaction also obeyed a typical Michaelis-Menten kinetics (Fig. 3.2d) [2, 5]. When alkanethiol terminated with ammonium was used to modify the AuNPs, the formed AuNP-based complexes were practically inactive. This control experiment conﬁrmed that the catalytic activity of AuNP-1 nanozyme was from the assembled monolayers rather than the AuNP core. The AuNP-1 nanozyme could also catalyze the cleavage of RNA dinucleotides (such as ApA, CpC, and UpU) [2]. Detailed studies revealed that the superior catalytic activity of AuNP-1 nanozyme could be attributed to its several unique features [2, 5]. First, it has been showed that the effective local concentration of guest molecules (e.g., the catalytic substrate HPNPP in this case) could be signiﬁcantly enhanced due to both the electrostatic and hydrophobic interactions between the positively charged

Fig. 3.2 a Comparison of catalyzed and uncatalyzed transphosphorylation of HPNPP. b Structure of Zn-1 complex. c Proposed catalytic pocket of AuNP-1 nanozyme. d Michaelis-Menten saturation kinetics of the transphosphorylation catalyzed by AuNP-1. E Dependence of the rate constant for the transphosphorylation of HPNPP with AuNP-1 on Zn ion concentration. c and d Adapted from Ref. [5], Copyright 2015, with permission from American Chemical Society. e Adapted from Ref. [2], Copyright 2004, with permission from John Wiley and Sons

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monolayer and the guest molecules [5, 6]. Second, the assembled catalytic moieties (i.e., the complex of TACN-Zn2+) were multivalent and exhibited cooperative behavior toward the catalysis. The cooperativity was indicated by the sigmoidal curve for zinc ion concentration-dependent catalytic activities (Fig. 3.2e) [2, 5]. The cooperative effect was further validated by experiments and theoretical analysis [7]. It suggested that two neighboring catalytic moieties (i.e., two TACN-Zn2+) were required to form a catalytic pocket for the cooperative catalysis (Fig. 3.2c) [2, 5, 7]. Such a catalytic pocket mimicked the ones in natural enzymes. Third, a 0.4 unit of pKa decrease of the assembled TACN-Zn2+ complexes due to the close proximity effect may also play a role in the enhanced activity [2]. Fourth, the strong Au-S interaction made the self-assembly very easy to be carried out. Also it endowed the assembled AuNP-based catalytic complexes with much higher stability compared with micelle-based systems [5]. Moreover, its catalytic activity could be rationally regulated. Since the catalytic activity of AuNP-1 nanozyme was from the complexed Zn2+, the activity could be reversibly switched off by using a Zn2+ chelating reagent and could be subsequently restored by re-adding Zn2+ [8]. For natural metallonucleases, their active sites have low dielectric constant (ε). As shown in Eq. 3.1 below, the electrostatic interaction between the enzyme and its substrate would be favored at active sites of low dielectric constant. To mimic such a unique microenvironment, low polarity should be introduced into the active sites. Eelectrostatic / ðQ1 Q2 Þ=ðe r1;2 Þ

ð3:1Þ

To test this hypothesis, AuNP-based nanozymes with different polarities have been prepared and their metallonuclease mimicking activities have been studied [9]. As shown in Fig. 3.3, AuNP-3 and AuNP-5 with lower polarities exhibited higher activities while AuNP-2 and AuNP-4 with higher polarities exhibited lower activities. Therefore, the catalytic activities were well correlated with the polarities

Fig. 3.3 a AuNP-based nanozymes with different polarities. b Transphosphorylation of HPNPP with AuNP-based nanozymes, highlighting the dianionic transition state. c Rate of HPNPP cleavage with different nanozymes. Adapted from Ref. [9], Copyright 2014, with permission from American Chemical Society

3.1 Metal Nanomaterials with Catalytic Monolayers (Type I)

35

of the assembled monolayers. The lowered polarities would enhance the electrostatic interaction between the dianionic transition state and the active sites of the nanozymes (i.e., Zn2+ complex), which therefore improved the catalytic activities. This study also suggested that catalytic activities of the nanozymes could be tuned by modulating the monolayers assembled. (b) Alkanethiol-protected AuNPs as RNase mimics: applications The above-mentioned RNA mimics have been explored for numerous interesting applications [10–12]. For instance, colorimetric detection of natural enzyme activity through catalytic signal ampliﬁcation with AuNP-1 nanozyme has been reported [10]. As shown in Fig. 3.4, a natural enzyme substrate (i.e., a peptide in this study) would interact strongly with AuNP-1 nanozyme and thus inhibit its RNase mimicking activity due to the shielding effect. The presence of the natural enzyme would cleave the substrate into smaller fragments and thus signiﬁcantly weaken the interactions with AuNP-1 nanozyme. Therefore, the cleaved fragments would be released from AuNP-1 nanozyme and thus restore the catalytic activity of AuNP-1 nanozyme. The restored AuNP-1 nanozyme would then convert HPNPP into the colored product p-nitrophenol, which was used as a reporter. Through the cascade ampliﬁcation, the natural enzyme could be determined with higher sensitivity and selectivity. Moreover, this design was a general approach, which has been extended to other enzymes by using the corresponding peptide substrates [10]. A sensitive and selective strategy for Hg2+ detection has been demonstrated [11]. AuNP-1 nanozyme had stronger afﬁnity toward a fluorescent reporter than thymidine probes (i.e., TDP, TMP, or cTMP), which resulted in the fluorescence quenching of the reporter. In the presence of Hg2+, the probes would form T-Hg2+T complex and the complex could compete against the fluorescent reporter for binding onto AuNP-1 nanozyme. Therefore, the reporter would be released from AuNP-1 nanozyme and its fluorescence was recovered. Hg2+ at nanomolar

Fig. 3.4 Detection of enzyme activity through catalytic signal ampliﬁcation with AuNP-1 nanozyme. Reprinted from Ref. [10], Copyright 2011, with permission from John Wiley and Sons

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Fig. 3.5 a Structure of BAPA. b Structure of AuNP-6 nanozyme. c Catalytic cleavage of BNP with DNase mimic. Adapted from Ref. [13], Copyright 2008, with permission from American Chemical Society

concentrations has been successfully detected with the proposed sensing strategy. It has also been demonstrated that AuNP-1 nanozyme could be used to mimic the key features of cellular signaling pathways [12]. (c) Alkanethiol-protected AuNPs as other enzyme mimics It is relatively straightforward to design other enzyme mimics by changing the terminal TACN moiety of the alkanethiol chain to other functional moieties [3, 4, 13–23]. For instance, a DNase mimic has been developed by assembling BAPA terminated alkanethiol onto AuNPs (Fig. 3.5) [13]. The cleavage of BNP (bis-p-nitrophenyl phosphate), a DNA model substrate, into MNP (p-nitrophenyl phosphate) and p-nitrophenolate has been accelerated with AuNP-6 nanozyme by 300,000folds over the background cleavage reaction. Moreover, DNA molecules (such as pBR 322 plasmid DNA) have been successfully cleaved with AuNP-6 nanozyme [13]. DNase could also be mimicked by using AuNPs modiﬁed with Ce(IV) complex terminated alkanethiol monolayers [15]. As many as 2.5 million-fold rate acceleration for the BNP cleavage was observed using the AuNPs-Ce(IV)-based nanozymes. The superior catalytic activity was also attributed to the unique features of the nanozyme, such as the cooperative catalysis. (d) RNase (DNase) mimics using other supporting cores Since AuNPs mainly acted as the supporting core, they could be replaced by other supporting materials. Several studies have showed that by assembling the catalytic moieties (such as TACN-Zn2+ complex) onto dendrimer, silica, etc., RNase and DNase mimics could be obtained (Fig. 3.6) [24–27]. Compared with the facile Au-S chemistry, the synthesis and puriﬁcation of these enzyme mimics are much more difﬁcult and time consuming. Other noble metal nanoparticles (such as AgNPs), in principle, could also be employed as the supporting core. However, no study has been reported, which might be due to the easy oxidation of AgNPs.

3.1 Metal Nanomaterials with Catalytic Monolayers (Type I)

37

Fig. 3.6 Dendrimer (a), silica particles (b), and resin (c) as inert supporting materials for catalytic monolayers. a Adapted from Ref. [24], Copyright 2007, with permission from American Chemical Society; b Adapted from Ref. [25], Copyright 2009, with permission from Royal Society of Chemistry; c Adapted from Ref. [26], Copyright 2009, with permission from Elsevier

3.1.2

AuNPs Protected by Alkanethiol with Non-covalently Assembled Catalytic Moieties

A few studies have showed that the catalytic moieties could be non-covalently assembled onto (or into) the alkanethiol-protected AuNPs [28–30]. As shown in Fig. 3.7a, the peptide ligation has been promoted when the two peptide fragments were electrostatically assembled onto trimethylammonium-functionalized AuNPs [28]. The transesteriﬁcation of the p-nitrophenyl ester of N-carboxybenzylphenylalanine was also signiﬁcantly enhanced by two orders of magnitude when both the substrate and the catalytic peptide were non-covalently assembled onto trimethylammonium functionalized AuNPs (Fig. 3.7b) [29]. For both of the examples, the non-covalent assembly was mainly driven by the electrostatic (and hydrophobic) interactions. The prominent catalytic activities were owing to the close proximity of the substrate and the catalyst as well as the unique microenvironment [28, 29]. Rotello and co-workers developed AuNPs-based nanozymes by encapsulating hydrophobic molecular catalysts (e.g., Ru complex and Pd complex) within the hydrophobic region of alkanethiol monolayers on AuNPs cores (Fig. 3.8a) [30]. To protect the encapsulated molecular catalysts from release, cucurbit[7]uril (CB[7]) was used to cap the head groups of the alkanethiol monolayers. When capped by CB[7], the nanozymes were inactive. The presence of a competing guest (i.e., 1-adamantylamine (ADA)) could bind onto CB[7] and form supramolecular complexes. Therefore, the molecular catalysts were exposed to the surrounding environment and the nanozymes were subsequently activated. Based on such as

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Fig. 3.7 Peptide ligation (a) and transesteriﬁcation (b) catalyzed by catalysts non-covalently assembled onto AuNPs. a Reprinted from Ref. [28], Copyright 2007, with permission from American Chemical Society; b Adapted from Ref. [29], Copyright 2012, with permission from American Chemical Society

supramolecular regulation mechanism, the activities of the nanozymes were modulated in vivo in living cells. As shown in Fig. 3.8, the uptaken nanozymes could activate nonfluorescent dye for cellular imaging. Moreover, the nanozyme could be used to activate pro-drug (i.e., pro-5FU) in living cells. With such in situ activation

Fig. 3.8 a Schematic of the nanozyme, consisting of an AuNP core and an alkanethiol monolayer with encapsulated catalysts. b Cellular uptake of the nanozyme and its regulation. c Activation of nonfluorescent dye with the nanozyme. d Activation of pro-drug dye with the nanozyme. Adapted from Ref. [30], Copyright 2015, with permission from Nature Publishing Group

3.1 Metal Nanomaterials with Catalytic Monolayers (Type I)

39

strategy, the toxic side effects of 5FU could be effectively minimized. This study may provide a facile strategy for tuning the activities of nanozymes in living cells.

3.1.3

AuNPs Protected by Thiolated Biomolecules

Other AuNPs-based nanozymes have been developed by assembling thiolated biomolecules on the AuNP cores [31–34]. Cao et al. has designed a nanozyme to mimic the function of RNA-induced silencing complex (RISC) machinery [31]. With the guidance of a regulatory ssRNA, a natural RISC would bind to the complementary target ssRNA and then silence its function by inducing target RNA cleavage with a nuclease contained within the RISC. To mimic the features of a RISC, both nucleases and regulatory ssRNA have been co-assembled onto an AuNP core (Fig. 3.9a). In the presence of a target ssRNA, the assembled regulatory ssRNA would form a duplex with the target ssRNA and thus bring it close to the assembled nuclease for cleavage. To demonstrate the hypothesis, the anti-HCV (hepatitis C virus) efﬁcacy of the nanozyme was evaluated using a HCV replicon

Fig. 3.9 a Schematic of the nanozyme for RNA silencing. b Anti-HCV effects of the anti-HCV nanozyme in FL-Neo cells. Adapted from Ref. [31], Copyright 2012, with permission from National Academy of Sciences

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cell culture system (i.e., an FL-Neo cell line). As shown in Fig. 3.9b, the HCV replication has been successfully inhibited with the nanozyme treatment. The in vivo efﬁcacy of the nanozyme was then evaluated using a xenotransplantation mouse model. Remarkably, the nanozyme treatment resulted in more than 99 % decrease of HCV RNA. Considering the non-detectable cellular interferon response, the designed nanozyme may be used as a potent nanomedicine for viral infections and cancers [31]. Other alternative approaches were developed for RNA interference-independent gene regulation [32, 33, 35, 36].

3.2

Metal Nanomaterials with Intrinsic Enzyme Mimicking Activities (Type II)

In 2004, the intrinsic oxidase mimicking activity of “naked” citrate-coated AuNPs was reported [37], since then metal nanomaterials with intrinsic enzyme mimicking activities have been extensively studied [38–64]. It has been showed that metal nanomaterials (such as Au, Ag, Pd, Pt, etc.) could mimic oxidase, SOD, catalase, peroxidase, etc. These nanozymes are unique in several aspects. First, most of them have multiple enzyme mimicking activities, which are dependent on their microenvironments. For instance, AuNPs exhibited catalase mimicking activity at high pH while they showed SOD-like activity at low pH [47]. Second, their enzyme mimicking activities could be tuned by forming alloys with other metals or by exposing speciﬁc facets [65]. Third, the catalytic activities could also be enhanced by exploring the plasmonic properties of noble metal nanomaterials [65].

3.2.1

Metal Nanomaterials as GOx Mimics

Glucose oxidase (GOx) catalyzes the oxidation of glucose into gluconic acid (gluconate) and H2O2 with oxygen. Rossi and co-workers reported the selective oxidation of glucose with oxygen using AuNPs load on carbon support as the catalyst [66]. The high selectivity was attributed to the two facts: ﬁrst, it has successfully avoided the isomerization of glucose to fructose under acidic conditions; second, it has enhanced the oxidation of the aldehydic group of glucose but did not affect the oxidation of the alcoholic group [66]. Later they discovered that even citrate-coated AuNPs of 3–6 nm could catalyze the aerobic oxidation of glucose with dissolved oxygen [37, 39, 40, 67]. The AuNPs catalyzed reaction was similar to the GOx catalyzed one in terms of the production of H2O2 and gluconate. Therefore, the AuNPs could be regarded as GOx mimics. Detailed mechanism studies suggested that the catalytic reaction followed an Eley–Rideal mechanism (Fig. 3.10) [39, 40, 67]. Briefly, a hydrated glucose anion ﬁrst interacted with Au atoms onto the AuNPs’ surface, which would

3.2 Metal Nanomaterials with Intrinsic Enzyme Mimicking Activities (Type II)

41

Fig. 3.10 Proposed molecular mechanism for the GOx-like activity of AuNPs. Reprinted from Ref. [67], Copyright 2006, with permission from John Wiley and Sons

lead to electron-rich Au species. Then by reacting with the electron-rich Au species and forming a dioxogold intermediate, oxygen was activated. Two electrons then transferred from glucose to oxygen via the dioxogold intermediate, producing H2O2 and gluconate [67]. The AuNPs catalyzed reaction also obeyed Michaelis–Menten kinetics [39, 40]. It also showed that the catalytic activities of the AuNPs were inversely proportional to their size, further conﬁrming their intrinsic enzyme mimicking properties [37]. Since Rossi’s work, numerous groups have studied the GOx mimicking activities of various AuNPs [38, 48–51, 68–83]. For instance, it showed that the nature of supports played a critical role in the catalytic activities of supported AuNPs as GOx mimics [50]. Besides AuNPs-based GOx mimics, a few other metal nanomaterials have also been explored for mimicking GOx [52–54]. For example, Pd nanoparticles on γ-Al2O3 support exhibited good selectivity toward glucose oxidation [52]. It has also demonstrated that Au atom decorated Pd nanoparticles exhibited higher catalytic activity toward glucose oxidation when compared with AuNPs, PdNPs, and Pd/Au alloys [54]. It further demonstrated that Au-containing bimetallic and trimetallic nanoparticles showed higher catalytic activities than monometallic ones [53]. The enhanced activities have been ascribed to several factors, such as electronic charge transfer effect among different metals, geometric effect, and structural changes [53].

3.2.2

Metal Nanomaterials as Multiple Enzyme Mimics

As mentioned above, many metal nanomaterials have exhibited multiple enzyme mimicking activities under different conditions [47, 65, 84–89]. For example, PtNPs encapsulated within ferritin have exhibited both peroxidase and catalase mimicking activities [84]. Due to the protection of the ferritin shell, the nanozymes showed high stability. The peroxidase mimicking activity was conﬁrmed by oxidizing colorless substrates (i.e., TMB and DAB) with H2O2 into the corresponding

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colored products in the presence of the nanozymes. The catalase mimicking activity was established by producing oxygen bubbles from H2O2 decomposition and by inhibiting the formation of hydroxyl radicals from H2O2 in the presence of the nanozymes. Moreover, they exhibited peroxidase-like activity at slightly acidic condition and physiological temperature. When the pH and reaction temperature increased, the catalase-like activity dominated [84]. The SOD and oxidase mimicking activities have also been observed in several nanomaterials [47, 86–88]. To better understand the multiple enzyme mimicking activities of metal nanomaterials, Wu, Gao and co-workers have carried out detailed computational studies [65, 89]. Au, Ag, Pt, and Pd nanomaterials exhibited pH-switchable peroxidase-like and catalase-like activities (i.e., they were peroxidase and catalase mimics at acidic and basic conditions, respectively) [89]. To unravel the origin of such pH-switchable catalytic activities, the H2O2 adsorption and the H2O2 decomposition behaviors on metal surfaces were calculated. First, the calculation of H2O2 adsorption on Au(111) surface indicated that H2O did not prevent H2O2 adsorption at neutral pH. At acidic pH, H would be pre-adsorbed, which in turn weakened the H2O2 adsorption on Au slightly. At basic pH, H2O2 interacted with Au atoms in the vicinities of the pre-adsorbed OH. As shown in Fig. 3.11a, it favored the base-like decomposition pathway at neutral conditions, which would produce adsorbed H2O (i.e., adsorbed H2O*) and adsorbed O (i.e., adsorbed O*). However, the adsorbed O may not form O2 due to the high energy barrier of 1.42 eV. As shown in Fig. 3.11B, at acidic conditions, it still preferred the base-like decomposition pathway. Due to the presence of pre-adsorbed H, H2O2 would be decomposed into an adsorbed H2O (i.e., adsorbed H2O*) and an adsorbed OH (i.e., OH*). The OH* would be converted into H2O* and O*. The formed O* subsequently oxidized organic substrates by abstracting H atom from them. Therefore, the Au(111) surface would act as a peroxidase mimic at acidic conditions. On the other hand, at basic conditions, it still preferred the acid-like decomposition pathway (Fig. 3.11c). In this case, one H from H2O2 would be react with the pre-adsorbed OH to form H2O* and HO*2. The newly formed HO*2 would transfer one H to another H2O2, resulting the formation of H2O* and O*2. Therefore, the Au(111) surface would act as a catalase mimic at basic conditions. The above-calculated results were consistent with the experimental results [89]. Further calculation revealed that for both Au(110) and Au(211) surfaces, they also favored base-like decomposition and acid-like decomposition pathway at acidic and basic conditions, respectively. In other words, both of them acted as peroxidase and catalase mimics at acidic and basic conditions, respectively. Since the enzyme mimicking activities were not dependent on the speciﬁc surfaces, it suggested that the catalytic activities were intrinsic properties. However, among the three surfaces, Au(111) surface exhibited the least catalytic activities due to the highest energy barriers [89]. To understand the different enzyme mimicking activities of different metal nanomaterials, the H2O2 decomposition on Ag(111), Pt(111), and Pd(111) surfaces was also calculated [89]. Several conclusions could be obtained from the calculation results. First, all of them followed the same reactions pathways as Au(111)

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Fig. 3.11 pH-switchable enzyme-mimic activities of metals. Calculated reaction energy proﬁles for H2O2 decomposition on the Au(111) surface in neutral (a), acidic (b) and basic (c) conditions (unit: eV). d Relationships between adsorption energies (Eads) and activation energies (Eact) for H2O2 decompositions on metal’s (111) surfaces at acidic (left) and basic (right) conditions. e TEM images of the nanorods. Enzyme-mimic activities of Au@Pd nanorods (0.1 nM) at 0.1 m PBS buffers with different pH values for peroxidase with f 20 mm H2O2 + 0.4 mm OPD and for catalase with h 20 mm H2O2, respectively. Peroxidase-like activity at pH = 4.5 (g) and catalase-like activity at pH = 7.4 (i) for the metals. Unless indicated, reaction temperature in (f–i)) is 30 °C. Reprinted from Ref. [89], Copyright 2015, with permission from Elsevier

surface did due to their structure similarities (i.e., they acted as peroxidase and catalase mimics at acidic and basic conditions, respectively). Second, the activation energies (Eact) of them for both mimics followed the order: Au(111) < Ag (111) < Pt(111) < Pd(111). Third, the adsorption energies (Eads) and activation energies (Eact) exhibited an approximate linear relationship (Fig. 3.11d). It also suggested that the afﬁnities of the metal surface toward H2O2 followed the order: Au(111) < Ag(111) < Pt(111) < Pd(111). Therefore, Eads could be practically used to estimate the relative catalytic activities of nanozymes [89].

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The above calculations indicated that for both mimics, their catalytic activities would follow the order: Au(111) < Ag(111) < Pt(111) < Pd(111). To test the hypothesis, four nanorods (i.e., Au, Au@Ag, Au@Pt, and Au@Pd) were synthesized and their activities were evaluated (Fig. 3.11e). First, the pH-switchable activities were observed for Au@Pd nanorods (Fig. 3.11f and 3.11h). Second, for different metal nanomaterials, both enzyme mimicking activities followed the order: Au(111), Ag(111) < Pt(111), Pd(111) (Fig. 3.11g and 3.11i), which was consistent with the calculations. Note that, the following orders were observed: Ag(111) < Au (111) and Pd(111) < Pt(111). Such deviation between the experimental and calculation results could be attributed to the following facts. For Ag(111), it could be easily oxidized and therefore affected its activities. For Pt(111), it had larger surface compared with Pd(111). Considering these facts, the calculations have provided mechanistic insights of the metals’ enzyme mimicking activities and have provided a way to predict the nanozymes’ activities [89]. Wu, Gao and co-workers also studied the origins of oxidase and SOD mimicking activities of Au, Ag, Pt, Pd, and their alloys [65]. For the oxidase mimicking activities, the adsorption of O2 and breakage of O–O bond (i.e., the dissociation of O2) should be critical since it would transfer the magnetic moments from 3O2 to the metal and thus allow originally spin forbidden 3O2 react with its substrate via O*. For Au(111), Ag(111), Pt(111), and Pd(111), though O2 could be adsorbed onto all of them and subsequently weakened the O–O bond of O2 in an energy favorable manner, only Pt(111) and Pd(111) exhibited low Eact and negative Er (reaction energy) values. The high Eact and positive Er values for Au(111) and Ag(111) suggested that Pt(111) and Pd(111) would exhibit oxidase mimicking activities while Au(111) and Ag(111) would not. Since the oxidase mimicking activities of AuNPs have been reported [37], there should be some factors responsible for such activities. To further reveal the origin of the AuNPs’ oxidase-like activities, the calculations for Au(110) and Au(211) surfaces were also carried out. Though Au (110) still did not show favorable oxidase mimicking activity, Au(211) did owing to the low Eact and negative Er. It suggested that the oxidase mimicking activities of the reported AuNPs might be originated from their high-energy facets, such as Au (211) [65]. Low-spin state 1O2 could be converted from 3O2 by the surface plasmon resonance of noble metals. Though the dissociation of 1O2 were kinetically easier than that of 3O2, the Eact values were still too large for Au(111) and Ag(111) surfaces. Therefore, the conversion of O2 from 3O2 to 1O2 would not substantially affect the metal-mediated O2 dissociation and thus their oxidase-like activities [65]. By forming alloys, the oxidase-like activities could be signiﬁcantly modulated [65]. The calculation results indicated that the formation of AuAg alloys has signiﬁcantly reduced the Eact values compared with Au and Ag themselves. Moreover, Er values for the alloys also became negatively. Therefore, the formation of AuAg alloys would enhance the oxidase mimicking activities of both Au and Ag. In contrast, the formation of alloys between Pd (or Pt) and Au led to the increase of Eact values and the positive Er values [65]. Therefore, the oxidase mimicking activities were disfavored for the AuPd or AuPt alloys. These results suggested a

3.2 Metal Nanomaterials with Intrinsic Enzyme Mimicking Activities (Type II)

45

possible approach to modulating the metals’ oxidase mimicking activities (in both positive and negative manners). − ∙ Since O∙− 2 radical can easily react with H2O to produce OH and HO2, the SOD mimicking activities of metal nanomaterials are mainly due to their capability for rearrange HO∙2 into H2O2 and O2. The calculation results showed that the Eact values for the rearrangement on both Au(111) and Pt(111) were very small, indicating that both of the metals could act as high efﬁcient SOD mimics [65].

3.2.3

Applications

Along with exploring the mechanisms of the metal-based nanozymes, they have also been widely used for various applications [79, 80, 86, 90–96]. (a) Immunoassays The metal nanomaterials-based oxidase, peroxidase, and even catalase mimics have been employed for immunoassays [86, 91, 95, 97–101]. For instance, sandwich assays for interleukin 2 (IL-2, a cytokine) have been developed with Au@Pt nanorods [86]. As shown in Fig. 3.12, both the oxidase and peroxidase mimicking activities of the Au@Pt nanorods could be employed for detection. In both cases, colorless TMB would be oxidized into colored products when IL-2 was present [86]. When the nanozymes were conjugated with tumor cell targeting molecules, the conjugates could be used for tumor cell immunoassay. For instance, when Au nanoclusters decorated graphene oxide was labeled with folic acid, the conjugates showed peroxidase-like activity and have been used for selectively quantifying MCF-7 tumor cells [98]. Using Pt nanoparticles as catalase mimics, a volumetric bar-chart chip has been developed for detection of biomarkers both in serum and on cell surface [99]. An integrin speciﬁc peptide was used to modify AuNPs-based peroxidase mimics. The obtained conjugates were then used as speciﬁc probes for cancer detection [101]. (b) Glucose and other bioactive small molecules detection By combing GOx with nanomaterials-based peroxidase mimics, glucose could be detected [58, 64, 87, 102–104]. Due to high speciﬁcity of natural GOx, these assays exhibited high selectivity toward glucose detection. Since AuNPs could act as GOx mimics, they were combined with hemin (a peroxidase mimic) together for colorimetric detection of glucose [81]. The selectivity of AuNPs-based GOx mimics remained to be studied. In principle, when a natural oxidase was combined with nanomaterials-based peroxidase mimics, the corresponding oxidase substrate as the target of interest could be determined (also see Tables A1 and A2). For example, a colorimetric assay for cholesterol was developed by combining cholesterol oxidase with Pt nanoparticles-based peroxidase mimics [64]. More interestingly, sarcosine, a

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Fig. 3.12 Immunoassays for interleukin 2. a Au@Pt nanorods-based assays. b Detection of IL-2 using Au@Pt nanorods’ oxidase (i.e., without H2O2) or peroxidase (i.e., with H2O2) mimicking activities. Reprinted from Ref. [86], Copyright 2011, with permission from Elsevier

potential biomarker for prostate cancer, in clinical samples has been successfully determined by using sarcosine oxidase and Pd nanoparticles-based peroxidase mimics [105]. (c) Detection of analytes by modulating nanozymes’ activities The nanozymes’ activities could be modulated by changing their sizes, surface coating, etc. Based on these phenomena, numerous strategies have been developed for sensing analytes of interest [78, 106–113].

3.2 Metal Nanomaterials with Intrinsic Enzyme Mimicking Activities (Type II)

47

Fan, Li, and co-workers found that the catalytic activities of AuNPs-based GOx mimics were controlled in a self-limited manner [107]. As discussed in Chap. 2, ssDNA and dsDNA have different afﬁnities toward AuNPs. By combing the AuNPs’ GOx mimicking activities with DNA modulation, a general sensing platform was developed (Fig. 3.13) [106]. The probe ssDNA would interact with AuNPs nanozymes and thus inhibited their catalytic activities. The presence of targets (such as a complementary ssDNA, a complementary miRNA, or an analyte for an aptamer if the probe ssDNA was an aptamer), the probe ssDNA would form a complex with its target and thus recover the activity of AuNPs. The nanozymes activities were then monitored with suitable output signals. For example, when it was coupled with HRP, either colorimetric or chemiluminescent signal would be produced. The intrinsic plasmonoic signals of the AuNPs could also be used for signaling [106]. Inspired by this work, several reports showed that other functional nucleic acids (including aptamers) could be used to modulate the nanozymes’ activities [108, 109, 111, 114, 115]. For example, a colorimetric method for the detection of kanamycin has been developed [108]. Kanamycin is an aminoglycoside antibiotic widely used in veterinary medicine. Its aptamer would bind onto AuNPs and inhibit their peroxidase-like activities. The speciﬁc interaction between kanamycin and its aptamer would recover the inhibited activities of the nanozymes. Via such a switchable strategy, kanamycin has been detected with good sensitivity and selectivity. Using the same principle, Li et al. reported the colorimetric detection of ricin with its aptamer and peroxidase-like AuNPs [115]. Besides DNA, other biomolecules could also be used to modulate the nanozymes activities and to develop biosensors [78, 113, 116]. Li and co-workers found that melamine could signiﬁcantly improve the peroxidase-like activity of AuNPs [116]. By making use of such enhancement effect, they proposed a colorimetric method for melamine detection (Fig. 3.14). The developed method was robust

Fig. 3.13 Illustration of the GOx-like catalytic activity of AuNPs regulated by DNA hybridization, which can be either ampliﬁed by HRP cascaded color or chemiluminescence variations (path a) or lead to nanoplasmonic changes owing to size enlargement (path b). Orange strand = target, green strand = adsorption probe. Reprinted from Ref. [106], Copyright 2011, with permission from John Wiley and Sons

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Fig. 3.14 Detection of melamine based on its enhancement toward the peroxidase-like activity of AuNPs. Reprinted from Ref. [116], Copyright 2014, with permission from Elsevier

Fig. 3.15 Detection of Hg2+ based on its inhibition toward the peroxidase-like activity of PtNPs. Reprinted from Ref. [117], Copyright 2015, with permission from Elsevier

enough that it has been employed to detect spiked melamine in raw milk and milk powder [116]. Metal ions have also been used to modulate the nanozymes’ activities [117, 118]. As shown in Fig. 3.15, the peroxidase-like activity of PtNPs could be selectively inhibited by Hg2+ due to the speciﬁc aurophilic/metallophilic interactions between Hg2+ and Pt0 [117]. Based on such speciﬁc inhibition, Hg2+ has been selectively detected against several other metal ions (such as Na+, Mg2+, Ca2+, Mn2+, Ni2+, Zn2+, Co2+, Cu2+, Pd2+, Cd2+, Fe3+, and Au3+). (d) Other applications Other potential applications of metal nanomaterials-based nanozymes have also been explored [61, 119]. For instance, Qu, Ren, and co-workers have studied the antibacterial activity of AuNPs encapsulated within mesoporous silica [119]. The nanozymes exhibited both oxidase and peroxidase mimicking activities. Since ROS ∙ (reactive oxygen species) species (such as O∙− 2 and HO ) were involved in the mimicking activities, it was reasonable to test the nanozymes’ antibacterial activity. As expected, the nanozymes showed antibacterial properties against both Gram-negative and Gram-positive bacteria [119].

References

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References 1. Love, J. C., Estroff, L. A., Kriebel, J. K., Nuzzo, R. G., & Whitesides, G. M. (2005). Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chemical Reviews, 105, 1103–1169. 2. Manea, F., Houillon, F. B., Pasquato, L., & Scrimin, P. (2004). Nanozymes: Gold-nanoparticle-based transphosphorylation catalysts. Angewandte Chemie-International Edition, 43, 6165–6169. 3. Levy, R. (2006). Peptide-capped gold nanoparticles: Towards artiﬁcial proteins. ChemBioChem, 7, 1141–1145. 4. Mancin, F., Prins, L. J., & Scrimin, P. (2013). Catalysis on gold-nanoparticle-passivating monolayers. Current Opinion in Colloid & Interface Science, 18, 61–69. 5. Prins, L. J. (2015). Emergence of complex chemistry on an organic monolayer. Accounts of Chemical Research, 48, 1920–1928. 6. Pieters, G., Pezzato, C., & Prins, L. J. (2013). Controlling supramolecular complex formation on the surface of a monolayer-protected gold nanoparticle in water. Langmuir, 29, 7180–7185. 7. Zaupa, G., Mora, C., Bonomi, R., Prins, L. J., & Scrimin, P. (2011). Catalytic self-assembled monolayers on Au nanoparticles: The source of catalysis of a transphosphorylation reaction. Chemistry-A European Journal, 17, 4879–4889. 8. Pieters, G., Pezzato, C., & Prins, L. J. (2012). Reversible control over the valency of a nanoparticle-based supramolecular system. Journal of the American Chemical Society, 134, 15289–15292. 9. Diez-Castellnou, M., Mancin, F., & Scrimin, P. (2014). Efﬁcient phosphodiester cleaving nanozymes resulting from multivalency and local medium polarity control. Journal of the American Chemical Society, 136, 1158–1161. 10. Bonomi, R., Cazzolaro, A., Sansone, A., Scrimin, P., & Prins, L. J. (2011). Detection of enzyme activity through catalytic signal ampliﬁcation with functionalized gold nanoparticles. Angewandte Chemie-International Edition, 50, 2307–2312. 11. Maiti, S., Pezzato, C., Martin, S. G., & Prins, L. J. (2014). Multivalent interactions regulate signal transduction in a self-assembled Hg2+ sensor. Journal of the American Chemical Society, 136, 11288–11291. 12. Pezzato, C., & Prins, L. J. (2015). Transient signal generation in a self-assembled nanosystem fueled by ATP. Nature Communications, 6, 7790. 13. Bonomi, R., Selvestrel, F., Lombardo, V., Sissi, C., Polizzi, S., Mancin, F., et al. (2008). Phosphate diester and DNA hydrolysis by a multivalent, nanoparticle-based catalyst. Journal of the American Chemical Society, 130, 15744–15745. 14. Pengo, P., Baltzer, L., Pasquato, L., & Scrimin, P. (2007). Substrate modulation of the activity of an artiﬁcial nanoesterase made of peptide-functionalized gold nanoparticles. Angewandte Chemie-International Edition, 46, 400–404. 15. Bonomi, R., Scrimin, P., & Mancin, F. (2010). Phosphate diesters cleavage mediated by Ce (IV) complexes self-assembled on gold nanoparticles. Organic & Biomolecular Chemistry, 8, 2622–2626. 16. Sheet, D., Halder, P., & Paine, T. K. (2013). Enhanced reactivity of a biomimetic iron(II) alpha-keto acid complex through immobilization on functionalized gold nanoparticles. Angewandte Chemie-International Edition, 52, 13314–13318. 17. Salvio, R., & Cincotti, A. (2014). Guanidine based self-assembled monolayers on Au nanoparticles as artiﬁcial phosphodiesterases. RSC Advances, 4, 28678–28682. 18. Pieters, G., & Prins, L. J. (2012). Catalytic self-assembled monolayers on gold nanoparticles. New Journal of Chemistry, 36, 1931–1939. 19. Kisailus, D., Najarian, M., Weaver, J. C., & Morse, D. E. (2005). Functionalized gold nanoparticles mimic catalytic activity of a polysiloxane-synthesizing enzyme. Advanced Materials, 17, 1234–1239.

50

3 Metal-Based Nanomaterials for Nanozymes

20. Yapar, S., Oikonomou, M., Veldersb, A. H., & Kubik, S. (2015). Dipeptide recognition in water mediated by mixed monolayer protected gold nanoparticles. Chemical Communications, 51, 14247–14250. 21. Li, X., Qi, Z., Liang, K., Bai, X., Xu, J., Liu, J., et al. (2008). An artiﬁcial supramolecular nanozyme based on beta-cyclodextrin-modiﬁed gold nanoparticles. Catalysis Letters, 124, 413–417. 22. Zhang, Z., Fu, Q., Huang, X., Xu, J., Liu, J., & Shen, J. (2009). Construction of the active site of metalloenzyme on au nc micelles. Chinese Journal of Chemistry, 27, 1215–1220. 23. Zhang, Z., Fu, Q., Li, X., Huang, X., Xu, J., Shen, J., et al. (2009). Self-assembled gold nanocrystal micelles act as an excellent artiﬁcial nanozyme with ribonuclease activity. Journal of Biological Inorganic Chemistry, 14, 653–662. 24. Martin, M., Manea, F., Fiammengo, R., Prins, L. J., Pasquato, L., & Scrimin, P. (2007). Metallodendrimers as transphosphorylation catalysts. Journal of the American Chemical Society, 129, 6982–6983. 25. Bodsgard, B. R., Clark, R. W., Ehrbar, A. W., Burstyn, J. N. (2009). Silica-bound copper(II) triazacyclononane as a phosphate esterase: Effect of linker length and surface hydrophobicity. Dalton Transactions, 2365–2373. 26. Zaupa, G., Prins, L. J., & Scrimin, P. (2009). Resin-supported catalytic dendrimers as multivalent artiﬁcial metallonucleases. Bioorganic & Medicinal Chemistry Letters, 19, 3816–3820. 27. Savelli, C., & Salvio, R. (2015). Guanidine-based polymer brushes grafted onto silica nanoparticles as efﬁcient artiﬁcial phosphodiesterases. Chemistry-A European Journal, 21, 5856–5863. 28. Fillon, Y., Verma, A., Ghosh, P., Ernenwein, D., Rotello, V. M., & Chmielewski, J. (2007). Peptide ligation catalyzed by functionalized gold nanoparticles. Journal of the American Chemical Society, 129, 6676–6677. 29. Zaramella, D., Scrimin, P., & Prins, L. J. (2012). Self-assembly of a catalytic multivalent peptide-nanoparticle complex. Journal of the American Chemical Society, 134, 8396–8399. 30. Tonga, G. Y., Jeong, Y., Duncan, B., Mizuhara, T., Mout, R., Das, R., et al. (2015). Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts. Nature Chemistry, 7, 597–603. 31. Wang, Z. L., Liu, H. Y., Yang, S. H., Wang, T., Liu, C., & Cao, Y. C. (2012). Nanoparticle-based artiﬁcial RNA silencing machinery for antiviral therapy. Proceedings of the National Academy of Sciences of the United States of America, 109, 12387–12392. 32. Yehl, K., Joshi, J. R., Greene, B. L., Dyer, R. B., Nahta, R., & Salaita, K. (2012). Catalytic deoxyribozyme-modiﬁed nanoparticles for RNAi-independent gene regulation. ACS Nano, 6, 9150–9157. 33. Patel, S., Jung, D., Yin, P. T., Carlton, P., Yamamoto, M., Bando, T., et al. (2014). Nanoscript: A nanoparticle-based artiﬁcial transcription factor for effective gene regulation. ACS Nano, 8, 8959–8967. 34. Patel, S., Yin, P. T., Sugiyama, H., & Lee, K.-B. (2015). Inducing stem cell myogenesis using nanoscript. ACS Nano, 9, 6909–6917. 35. Wang, Z., Wang, Z., Liu, D., Yan, X., Wang, F., Niu, G., et al. (2014). Biomimetic RNA-silencing nanocomplexes: Overcoming multidrug resistance in cancer cells. Angewandte Chemie-International Edition, 53, 1997–2001. 36. Rouge, J. L., Sita, T. L., Hao, L., Kouri, F. M., Briley, W. E., Stegh, A. H., et al. (2015). Ribozyme-spherical nucleic acids. Journal of the American Chemical Society, 137, 10528–10531. 37. Comotti, M., Della Pina, C., Matarrese, R., Rossi, M. (2004). The catalytic activity of “naked” gold particles. Angewandte Chemie-International Edition, 43, 5812–5815. 38. Wei, H., & Wang, E. K. (2013). Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artiﬁcial enzymes. Chemical Society Reviews, 42, 6060–6093. 39. Beltrame, P., Comotti, M., Della Pina, C., & Rossi, M. (2004). Aerobic oxidation of glucose I. Enzymatic catalysis. Journal of Catalysis, 228, 282–287.

References

51

40. Beltrame, P., Comotti, M., Della Pina, C., Rossi, M. (2006) Aerobic oxidation of glucose II. catalysis by colloidal gold. Applied Catalysis A-General, 297, 1–7. 41. Lin, Y. H., Ren, J. S., & Qu, X. G. (2014). Nano-gold as artiﬁcial enzymes: Hidden talents. Advanced Materials, 26, 4200–4217. 42. Della Pina, C., Falletta, E., Rossi, M. (2012). Update on selective oxidation using gold. Chemical Society Reviews, 41, 350–369. 43. Tan, X., Deng, W., Liu, M., Zhang, Q., Wang, Y. (2009). Carbon nanotube-supported gold nanoparticles as efﬁcient catalysts for selective oxidation of cellobiose into gluconic acid in aqueous medium. Chemical Communications, 7179–7181. 44. Zhang, J., Liu, X., Hedhili, M. N., Zhu, Y., & Han, Y. (2011). Highly selective and complete conversion of cellobiose to gluconic acid over Au/Cs2HPW12O40 nanocomposite catalyst. ChemCatChem, 3, 1294–1298. 45. An, D., Ye, A., Deng, W., Zhang, Q., & Wang, Y. (2012). Selective conversion of cellobiose and cellulose into gluconic acid in water in the presence of oxygen, catalyzed by polyoxometalate-supported gold nanoparticles. Chemistry-A European Journal, 18, 2938–2947. 46. Lee, L.-C., & Zhao, Y. (2014). Metalloenzyme-mimicking supramolecular catalyst for highly active and selective intramolecular alkyne carboxylation. Journal of the American Chemical Society, 136, 5579–5582. 47. He, W. W., Zhou, Y. T., Warner, W. G., Hu, X. N., Wu, X. C., Zheng, Z., et al. (2013). Intrinsic catalytic activity of Au nanoparticles with respect to hydrogen peroxide decomposition and superoxide scavenging. Biomaterials, 34, 765–773. 48. Miedziak, P. J., Alshammari, H., Kondrat, S. A., Clarke, T. J., Davies, T. E., Morad, M., et al. (2014). Base-free glucose oxidation using air with supported gold catalysts. Green Chemistry, 16, 3132–3141. 49. Wang, Y., Van de Vyver, S., Sharma, K. K., & Roman-Leshkov, Y. (2014). Insights into the stability of gold nanoparticles supported on metal oxides for the base-free oxidation of glucose to gluconic acid. Green Chemistry, 16, 719–726. 50. Ishida, T., Kinoshita, N., Okatsu, H., Akita, T., Takei, T., & Haruta, M. (2008). Influence of the support and the size of gold clusters on catalytic activity for glucose oxidation. Angewandte Chemie-International Edition, 47, 9265–9268. 51. Zhan, P., Wang, Z.-G., Li, N., & Ding, B. (2015). Engineering gold nanoparticles with DNA ligands for selective catalytic oxidation of chiral substrates. ACS Catalysis, 5, 1489–1498. 52. Liang, X., Liu, C.-J., & Kuai, P. (2008). Selective oxidation of glucose to gluconic acid over argon plasma reduced Pd/Al2O3. Green Chemistry, 10, 1318–1322. 53. Zhang, H., & Toshima, N. (2013). Glucose oxidation using Au-containing bimetallic and trimetallic nanoparticles. Catalysis Science & Technology, 3, 268–278. 54. Zhang, H., Watanabe, T., Okumura, M., Haruta, M., & Toshima, N. (2012). Catalytically highly active top gold atom on palladium nanocluster. Nature Materials, 11, 49–52. 55. Lin, Y. H., Zhao, A. D., Tao, Y., Ren, J. S., & Qu, X. G. (2013). Ionic liquid as an efﬁcient modulator on artiﬁcial enzyme system: Toward the realization of high-temperature catalytic reactions. Journal of the American Chemical Society, 135, 4207–4210. 56. Liu, Y., Purich, D. L., Wu, C. C., Wu, Y., Chen, T., Cui, C., et al. (2015). Ionic functionalization of hydrophobic colloidal nanoparticles to form ionic nanoparticles with enzyme like properties. Journal of the American Chemical Society, 137, 14952–14958. 57. Wang, S., Chen, W., Liu, A. L., Hong, L., Deng, H. H., & Lin, X. H. (2012). Comparison of the peroxidase-like activity of unmodiﬁed, amino-modiﬁed, and citrate-capped gold nanoparticles. ChemPhysChem, 13, 1199–1204. 58. Jv, Y., Li, B. X., & Cao, R. (2010). Positively-charged gold nanoparticles as peroxidiase mimic and their application in hydrogen peroxide and glucose detection. Chemical Communications, 46, 8017–8019. 59. Jiang, H., Chen, Z. H., Cao, H. Y., & Huang, Y. M. (2012). Peroxidase-like activity of chitosan stabilized silver nanoparticles for visual and colorimetric detection of glucose. Analyst, 137, 5560–5564.

52

3 Metal-Based Nanomaterials for Nanozymes

60. Zhang, K., Hu, X. N., Liu, J. B., Yin, J. J., Hou, S. A., Wen, T., et al. (2011). Formation of PdPt alloy nanodots on gold nanorods: Tuning oxidase-like activities via composition. Langmuir, 27, 2796–2803. 61. Shibuya, S., Ozawa, Y., Watanabe, K., Izuo, N., Toda, T., Yokote, K., et al. (2014). Palladium and platinum nanoparticles attenuate aging-like skin atrophy via antioxidant activity in mice. PLoS ONE, 9, 109288. 62. Chen, Z., Zhao, C., Ju, E., Ji, H., Ren, J., Binks, B. P., et al. (2016). Design of surface-active artiﬁcial enzyme particles to stabilize pickering emulsions for high-performance biphasic biocatalysis. Advanced Materials, 28, 1682–1688. 63. Fu, Y., Zhao, X. Y., Zhang, J. L., & Li, W. (2014). DNA-based platinum nanozymes for peroxidase mimetics. Journal of Physical Chemistry C, 118, 18116–18125. 64. Zhang, W., Liu, X. Y., Walsh, D., Yao, S. Y., Kou, Y., & Ma, D. (2012). Caged-protein-conﬁned bimetallic structural assemblies with mimetic peroxidase activity. Small (Weinheim an der Bergstrasse, Germany), 8, 2948–2953. 65. Shen, X., Liu, W., Gao, X., Lu, Z., Wu, X., & Gao, X. (2015). Mechanisms of oxidase and superoxide dismutation-like activities of gold, silver, platinum, and palladium, and their alloys: A general way to the activation of molecular oxygen. Journal of the American Chemical Society, 137, 15882–15891. 66. Biella, S., Prati, L., & Rossi, M. (2002). Selective oxidation of D-glucose on gold catalyst. Journal of Catalysis, 206, 242–247. 67. Comotti, M., Della Pina, C., Falletta, E., & Rossi, M. (2006). Aerobic oxidation of glucose with gold catalyst: Hydrogen peroxide as intermediate and reagent. Advanced Synthesis & Catalysis, 348, 313–316. 68. Lang, N. J., Liu, B. W., & Liu, J. W. (2014). Characterization of glucose oxidation by gold nanoparticles using nanoceria. Journal of Colloid and Interface Science, 428, 78–83. 69. Delidovich, I. V., Moroz, B. L., Taran, O. P., Gromov, N. V., Pyrjaev, P. A., Prosvirin, I. P., et al. (2013). Aerobic selective oxidation of glucose to gluconate catalyzed by Au/Al2O3 and Au/C: Impact of the mass-transfer processes on the overall kinetics. Chemical Engineering Journal, 223, 921–931. 70. Odrozek, K., Maresz, K., Koreniuk, A., Prusik, K., & Mrowiec-Bialon, J. (2014). Amine-stabilized small gold nanoparticles supported on A1SBA-15 as effective catalysts for aerobic glucose oxidation. Applied Catalysis A-General, 475, 203–210. 71. Zhang, H., Lu, L., Cao, Y., Du, S., Cheng, Z., & Zhang, S. (2014). Fabrication of catalytically active Au/Pt/Pd trimetallic nanoparticles by rapid injection of NaBH4. Materials Research Bulletin, 49, 393–398. 72. Ishida, T., Okamoto, S., Makiyama, R., & Haruta, M. (2009). Aerobic oxidation of glucose and 1-phenylethanol over gold nanoparticles directly deposited on ion-exchange resins. Applied Catalysis A-General, 353, 243–248. 73. Okatsu, H., Kinoshita, N., Akita, T., Ishida, T., & Haruta, M. (2009). Deposition of gold nanoparticles on carbons for aerobic glucose oxidation. Applied Catalysis A-General, 369, 8–14. 74. Benko, T., Beck, A., Geszti, O., Katona, R., Tungler, A., Frey, K., et al. (2010). Selective oxidation of glucose versus CO oxidation over supported gold catalysts. Applied Catalysis A-General, 388, 31–36. 75. Shi, L., Liu, K., Zou, X., Yin, M., & Suo, Z. (2010). Selective oxidation of glucose in the presence of PVP-protected colloidal gold solutions. Chinese Journal of Catalysis, 31, 661–665. 76. Ma, C., Xue, W., Li, J., Xing, W., & Hao, Z. (2013). Mesoporous carbon-conﬁned Au catalysts with superior activity for selective oxidation of glucose to gluconic acid. Green Chemistry, 15, 1035–1041. 77. Yin, H., Zhou, C., Xu, C., Liu, P., Xu, X., & Ding, Y. (2008). Aerobic oxidation of D-glucose on support-free nanoporous gold. Journal of Physical Chemistry C, 112, 9673–9678.

References

53

78. Wang, G. L., Jin, L. Y., Dong, Y. M., Wu, X. M., & Li, Z. J. (2015). Intrinsic enzyme mimicking activity of gold nanoclusters upon visible light triggering and its application for colorimetric trypsin detection. Biosensors & Bioelectronics, 64, 523–529. 79. Wang, L. H., Zeng, Y., Shen, A. G., Zhou, X. D., & Hu, J. M. (2015). Three dimensional nano-assemblies of noble metal nanoparticle-inﬁnite coordination polymers as speciﬁc oxidase mimetics for degradation of methylene blue without adding any cosubstrate. Chemical Communications, 51, 2052–2055. 80. Zhou, H., Han, T., Wei, Q., & Zhang, S. (2016). Efﬁcient enhancement of electrochemiluminescence from cadmium sulﬁde quantum dots by glucose oxidase mimicking gold nanoparticles for highly sensitive assay of methyltransferase activity. Analytical Chemistry, 88, 2976–2983. 81. Lin, Y. H., Wu, L., Huang, Y. Y., Ren, J. S., & Qu, X. G. (2015). Positional assembly of hemin and gold nanoparticles in graphene-mesoporous silica nanohybrids for tandem catalysis. Chemical Science, 6, 1272–1276. 82. Huang, Y., Lin, Y., Ran, X., Ren, J., Qu, X. (2016) Self-assembly and compartmentalization of nanozymes in mesoporous silica-based nanoreactors. Chemistry (Weinheim an der Bergstrasse, Germany), 22, 5705–5711. 83. Lin, Y. H., Li, Z. H., Chen, Z. W., Ren, J. S., & Qu, X. G. (2013). Mesoporous silica-encapsulated gold nanoparticles as artiﬁcial enzymes for self-activated cascade catalysis. Biomaterials, 34, 2600–2610. 84. Fan, J., Yin, J.-J., Ning, B., Wu, X., Hu, Y., Ferrari, M., et al. (2011). Direct evidence for catalase and peroxidase activities of ferritin-platinum nanoparticles. Biomaterials, 32, 1611–1618. 85. He, W., Zhou, Y.-T., Wamer, W. G., Boudreau, M. D., & Yin, J.-J. (2012). Mechanisms of the pH dependent generation of hydroxyl radicals and oxygen induced by Ag nanoparticles. Biomaterials, 33, 7547–7555. 86. He, W. W., Liu, Y., Yuan, J. S., Yin, J. J., Wu, X. C., Hu, X. N., et al. (2011). Au@Pt nanostructures as oxidase and peroxidase mimetics for use in immunoassays. Biomaterials, 32, 1139–1147. 87. Liu, J. B., Hu, X. N., Hou, S., Wen, T., Liu, W. Q., Zhu, X., et al. (2012). Au@Pt core/shell nanorods with peroxidase- and ascorbate oxidase-like activities for improved detection of glucose. Sensors and Actuators B-Chemical, 166, 708–714. 88. Hu, X. N., Saran, A., Hou, S., Wen, T., Ji, Y. L., Liu, W. Q., et al. (2013). Au@PtAg core/shell nanorods: tailoring enzyme-like activities via alloying. RSC Advances, 3, 6095–6105. 89. Li, J. N., Liu, W. Q., Wu, X. C., & Gao, X. F. (2015). Mechanism of pH-switchable peroxidase and catalase-like activities of gold, silver, platinum and palladium. Biomaterials, 48, 37–44. 90. Hu, D., Sheng, Z., Fang, S., Wang, Y., Gao, D., Zhang, P., et al. (2014). Folate receptor-targeting gold nanoclusters as fluorescence enzyme mimetic nanoprobes for tumor molecular colocalization diagnosis. Theranostics, 4, 142–153. 91. Wang, Z. F., Zheng, S., Cai, J., Wang, P., Feng, J., Yang, X., et al. (2013). Fluorescent artiﬁcial enzyme-linked immunoassay system based on Pd/C nanocatalyst and fluorescent chemodosimeter. Analytical Chemistry, 85, 11602–11609. 92. He, S. B., Wu, G. W., Deng, H. H., Liu, A. L., Lin, X. H., Xia, X. H., et al. (2014). Choline and acetylcholine detection based on peroxidase-like activity and protein antifouling property of platinum nanoparticles in bovine serum albumin scaffold. Biosensors & Bioelectronics, 62, 331–336. 93. Zheng, C., Zheng, A. X., Liu, B., Zhang, X. L., He, Y., Li, J., et al. (2014). One-pot synthesized DNA-templated Ag/Pt bimetallic nanoclusters as peroxidase mimics for colorimetric detection of thrombin. Chemical Communications, 50, 13103–13106. 94. Lin, X. Q., Deng, H. H., Wu, G. W., Peng, H. P., Liu, A. L., Lin, X. H., et al. (2015). Platinum nanoparticles/graphene-oxide hybrid with excellent peroxidase-like activity and its application for cysteine detection. Analyst, 140, 5251–5256.

54

3 Metal-Based Nanomaterials for Nanozymes

95. Xia, X. H., Zhang, J. T., Lu, N., Kim, M. J., Ghale, K., Xu, Y., et al. (2015). Pd-Ir core-shell nanocubes: A type of highly efﬁcient and versatile peroxidase mimic. ACS Nano, 9, 9994–10004. 96. Sun, Y., Wang, J., Li, W., Zhang, J., Zhang, Y., & Fu, Y. (2015). DNA-stabilized bimetallic nanozyme and its application on colorimetric assay of biothiols. Biosensors & Bioelectronics, 74, 1038–1046. 97. Zhao, Q., Huang, H., Zhang, L., Wang, L., Zeng, Y., Xia, X., et al. (2016). Strategy to fabricate naked-eye readout ultrasensitive plasmonic nanosensor based on enzyme mimetic gold nanoclusters. Analytical Chemistry, 88, 1412–1418. 98. Tao, Y., Lin, Y. H., Huang, Z. Z., Ren, J. S., & Qu, X. G. (2013). Incorporating graphene oxide and gold nanoclusters: A synergistic catalyst with surprisingly high peroxidase-like activity over a broad ph range and its application for cancer cell detection. Advanced Materials, 25, 2594–2599. 99. Song, Y. J., Xia, X. F., Wu, X. F., Wang, P., & Qin, L. D. (2014). Integration of platinum nanoparticles with a volumetric bar-chart chip for biomarker assays. Angewandte Chemie-International Edition, 53, 12451–12455. 100. Song, Y., Wang, Y., & Qin, L. (2013). A multistage volumetric bar chart chip for visualized quantiﬁcation of DNA. Journal of the American Chemical Society, 135, 16785–16788. 101. Gao, L., Liu, M. Q., Ma, G. F., Wang, Y. L., Zhao, L. N., Yuan, Q., et al. (2015). Peptide-conjugated gold nanoprobe: Intrinsic nanozyme-linked immunsorbant assay of integrin expression level on cell membrane. ACS Nano, 9, 10979–10990. 102. Han, M., Liu, S., Bao, J., & Dai, Z. (2012). Pd nanoparticle assemblies-as the substitute of HRP, in their biosensing applications for H2O2 and glucose. Biosensors & Bioelectronics, 31, 151–156. 103. Jiang, X., Sun, C. J., Guo, Y., Nie, G. J., & Xu, L. (2015). Peroxidase-like activity of apoferritin paired gold clusters for glucose detection. Biosensors & Bioelectronics, 64, 165–170. 104. Wang, Q., Zhang, L., Shang, C., Zhang, Z., & Dong, S. (2016). Triple-enzyme mimetic activity of nickel-palladium hollow nanoparticles and their application in colorimetric biosensing of glucose. Chemical Communications, 52, 5410–5413. 105. Lan, J., Xu, W., Wan, Q., Zhang, X., Lin, J., Chen, J., et al. (2014). Colorimetric determination of sarcosine in urine samples of prostatic carcinoma by mimic enzyme palladium nanoparticles. Analytica Chimica Acta, 825, 63–68. 106. Zheng, X. X., Liu, Q., Jing, C., Li, Y., Li, D., Luo, W. J., et al. (2011). Catalytic gold nanoparticles for nanoplasmonic detection of DNA hybridization. Angewandte Chemie-International Edition, 50, 11994–11998. 107. Luo, W. J., Zhu, C. F., Su, S., Li, D., He, Y., Huang, Q., et al. (2010). Self-catalyzed, self-limiting growth of glucose oxidase-mimicking gold nanoparticles. ACS Nano, 4, 7451–7458. 108. Sharma, T. K., Ramanathan, R., Weerathunge, P., Mohammadtaheri, M., Daima, H. K., Shukla, R., et al. (2014). Aptamer-mediated ‘turn-off/turn-on’ nanozyme activity of gold nanoparticles for kanamycin detection. Chemical Communications, 50, 15856–15859. 109. Weerathunge, P., Ramanathan, R., Shukla, R., Sharma, T. K., & Bansal, V. (2014). Aptamer-controlled reversible inhibition of gold nanozyme activity for pesticide sensing. Analytical Chemistry, 86, 11937–11941. 110. Daniel, M. C., & Astruc, D. (2004). Gold nanoparticles: Assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chemical Reviews, 104, 293–346. 111. Zhou, P., Jia, S., Pan, D., Wang, L., Gao, J., Lu, J., et al. (2015). Reversible regulation of catalytic activity of gold nanoparticles with DNA nanomachines. Scientiﬁc Reports, 5, 14402. 112. Hizir, M. S., Top, M., Balcioglu, M., Rana, M., Robertson, N. M., Shen, F. S., et al. (2016). Multiplexed activity of perauxidase: DNA-capped aunps act as adjustable peroxidase. Analytical Chemistry, 88, 600–605.

References

55

113. Lien, C. W., Huang, C. C., & Chang, H. T. (2012). Peroxidase-mimic bismuth-gold nanoparticles for determining the activity of thrombin and drug screening. Chemical Communications, 48, 7952–7954. 114. Zhan, P., Wang, J., Wang, Z.-G., & Ding, B. (2014). Engineering the pH-responsive catalytic behavior of aunps by DNA. Small (Weinheim an der Bergstrasse, Germany), 10, 399–406. 115. Hu, J. T., Ni, P. J., Dai, H. C., Sun, Y. J., Wang, Y. L., Jiang, S., et al. (2015). A facile label-free colorimetric aptasensor for ricin based on the peroxidase-like activity of gold nanoparticles. RSC Advances, 5, 16036–16041. 116. Ni, P. J., Dai, H. C., Wang, Y. L., Sun, Y. J., Shi, Y., Hu, J. T., et al. (2014). Visual detection of melamine based on the peroxidase-like activity enhancement of bare gold nanoparticles. Biosensors & Bioelectronics, 60, 286–291. 117. Li, W., Bin, C., Zhang, H. X., Sun, Y. H., Wang, J., Zhang, J. L., et al. (2015). BSA-stabilized Pt nanozyme for peroxidase mimetics and its application on colorimetric detection of mercury(II) ions. Biosensors & Bioelectronics, 66, 251–258. 118. Fu, Y., Zhang, H. X., Dai, S. D., Zhi, X., Zhang, J. L., & Li, W. (2015). Glutathione-stabilized palladium nanozyme for colorimetric assay of silver(I) ions. Analyst, 140, 6676–6683. 119. Tao, Y., Ju, E. G., Ren, J. S., & Qu, X. G. (2015). Bifunctionalized mesoporous silica-supported gold nanoparticles: Intrinsic oxidase and peroxidase catalytic activities for antibacterial applications. Advanced Materials, 27, 1097–1104.

Chapter 4

Metal Oxide-Based Nanomaterials for Nanozymes

Abstract Metal oxide-based nanomaterials have been extensively studied to mimic various natural enzymes due to their unique properties. In this chapter, several metal oxide-based nanozymes are discussed. First, the use of cerium oxide nanomaterials for mimicking natural enzymes (such as superoxide dismutase, catalase, oxidase, peroxidase, phosphatase, etc.) is discussed. Second, the use of iron oxide nanomaterials for peroxidase mimics and other mimics is covered. Third, the enzyme mimicking activities of other metal oxides (such as vanadium oxide, cobalt oxide, copper oxide, etc.) are discussed. The catalytic mechanisms are also discussed if they have been elucidated. Selected examples for broad applications are discussed, which cover from glucose detection, DNA detection, immunoassay, and immunostaining, to neuroprotection, cardioprotection, cancer therapy, and tissue engineering.

Keywords Nanozymes Artiﬁcial enzymes Enzyme mimics Metal oxide-based nanomaterials Cerium oxide Iron oxide Reactive oxygen species Oxidase mimics Glucose detection Brain chemistry

Metal oxide-based nanomaterials (such as cerium oxide and iron oxide) have been extensively studied to mimic various natural enzymes. These nanozymes have found broad applications in many areas, from bioanalysis to therapeutics. In this chapter, we will discuss the nanozymes based on these metal oxide nanomaterials.

4.1

Cerium Oxide

Cerium oxide nanomaterials (also called nanoceria) have been widely used as highly efﬁcient catalysts due to their unique properties (i.e., the presence of mixed valence states of Ce3+ and Ce4+ and highly mobile lattice oxygen) [1]. They have also been extensively explored for mimicking natural enzymes [2–8]. In 2005, Tarnuzzer, Seal and co-workers reported that vacancy engineered nanoceria could © The Author(s) 2016 X. Wang et al., Nanozymes: Next Wave of Artiﬁcial Enzymes, SpringerBriefs in Molecular Science, DOI 10.1007/978-3-662-53068-9_4

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protect normal but not tumor cells from radiation-induced damage [9]. Since then, a large number of studies have showed that nanoceria could mimic SOD, catalase, oxidase, peroxidase, phosphatase, etc. [10–35].

4.1.1

Cerium Oxide as SOD Mimics

(a) Catalytic activities and mechanisms In their seminal study, Tarnuzzer, Seal and co-workers attributed the protective role of the nanoceria to its free radicals elimination capability. It was suggested that the radicals could be eliminated by nanoceria via a Ce3 þ ! Ce4 þ ! Ce3 þ regeneration mechanism [9]. Self, Seal, and co-workers as well as other groups have then established the SOD mimicking activities of nanoceria [36–38]. Based on the competitive cytochrome C assay, H2O2 formation assay, and EPR measurements, Self et al. [36, 37] proposed that the nanoceria would exert the SOD-like activities via the mechanisms shown in Eqs. 4.1–4.2. A possible molecular mechanism was proposed (Fig. 4.1) [39]. However, more detailed studies are still needed to conﬁrm (or even modify) the proposed mechanism.

Fig. 4.1 Proposed molecular mechanisms for the SOD mimicking activity of nanoceria. Reprinted from Ref. [39], Copyright 2011, with permission from Royal Society of Chemistry

4.1 Cerium Oxide

59 4þ O ! O2 þ Ce3 þ 2 þ Ce

ð4:1Þ

3þ þ 2H þ ! H2 O2 þ Ce4 þ O 2 þ Ce

ð4:2Þ

The SOD-like catalytic activity of nanoceria was dependent on the redox state of surface cerium ions (i.e., the SOD-like activity was positively correlated with the ratio of Ce3+/Ce4+) [36, 37]. It was also found that the SOD mimicking activity of nanoceria was size dependent. Nanoceria larger than 5 nm did not show prominent SOD activity [36]. An interesting strategy has been proposed to endow the nanoceria larger than 5 nm with SOD mimicking activities [40]. When electrons were transferred either from a native SOD or other donors (e.g., an inorganic metal complex) to the nanoceria with large size, its superoxide-scavenging capability was restored. The transferred electrons would reduce Ce4+ to Ce3+ and thus improve the SOD-like activity [40]. The SOD mimicking activities of nanoceria could be modulated by other strategies [41–43]. For example, by doping with nanoceria with redox inactive Sm and Ti atoms, its catalytic activity could be reduced [41, 43]. (b) Applications Nanoceria-based SOD mimics have been used for various applications, ranging from anti-inflammation and neuroprotection to tissue engineering and cancer therapy [2, 44–46]. Neuroprotection. Numerous studies have demonstrated that nanoceria had neuroprotection functions [47–50]. In their pioneering study, McGinnis et al. showed that nanoceria could protect rat retina photoreceptor cells from light-induced degeneration (Fig. 4.2). The protection activity was probably due to the elimination of ROS (reactive oxygen species) by nanoceria. Encouragingly, the nanozymes showed therapeutic effects when they were administrated either before or even after light exposure [47]. In a later report, they showed that nanoceria exhibited long-term therapeutic effects of protecting photoreceptor cells from degeneration [48]. Using the very low density lipoprotein receptor knockout (vldlr–/–) mouse as a model, McGinnis et al. [49] demonstrated that nanoceria was effective against age-related macular degeneration diseases. Other groups have also demonstrated the neuroprotection roles of nanoceria in several disease models, such as adult rat spinal cord injury, brain ischemia, Alzheimer’s disease, autoimmune encephalomyelitis, etc. [51–55]. For example, using mouse hippocampal brain slice as an in vitro model of brain ischemia, it has showed that the treatment of nanoceria could signiﬁcantly reduce the ischemic cell death (Fig. 4.3) [52]. Detailed studies revealed that the concentrations of superoxide (O∙− 2 ) and nitric oxide were reduced by around 15 %. Moreover, the level of peroxynitrite-induced 3-nitrotyrosine was remarkably reduced by 70 %. Therefore, it was proposed that the nanozymes may protect the brain cells from ischemic injury by scavenging ROS and NOS (such as peroxynitrite, O∙− 2 , and nitric oxide) [52]. The nanozyme even protected cell from ischemic injury in living mice brains [53].

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Fig. 4.2 Intravitreal injection of nanoceria protected rat retina photoreceptor cells from light-induced degeneration. Reprinted from Ref. [47], Copyright 2006, with permission from Nature Publishing Group

To further improve the therapeutic efﬁcacy, one may conjugate speciﬁc recognition moieties onto the nanozymes for targeted therapy [55]. Cardioprotection. A few studies have showed that nanoceria possessed cardioprotective activities [56–58]. Traversa, Nardo, and co-workers showed that nanoceria protected cardiac progenitor cells, a valuable cell source for cardiac regenerative medicine, from oxidative stress [56]. For an in vivo mouse model with ischemic cardiomyopathy, the treatment with nanoceria effectively inhibited the progressive left ventricular dysfunction and dilatation. The therapeutic beneﬁts of the nanozymes were due to the inhibition of myocardial oxidative stress, ER stress and inflammatory processes, which were evidenced by the decrease of pro-inflammatory cytokines (such as tumor necrosis factor-α and interleukin-1β) and downregulation of endoplasmic reticulum stress-associated genes [59]. Heart hypertrophy following pulmonary arterial hypertension could also be attenuated by nanoceria treatment [58]. Cancer therapy. Researchers have used nanoceria to treat cancers [60–63]. Cellular studies demonstrated the feasibility of using nanoceria for cancer therapy. Due to the Warburg effect, the nanozyme would beneﬁt stromal cells by eliminating the elevated ROS. At the same time, the nanozyme would inhibit tumor cells’ metastatic spread by inhibiting the myoﬁbroblasts formation, etc. [60]. The in vivo anticancer activities of the nanoceria were evaluated using mice with xenografted melanoma. The treatment with nanoceria led to signiﬁcantly smaller tumor volume

4.1 Cerium Oxide

61

Fig. 4.3 Neuroprotective effect of nanoceria treatment after brain ischemia. Nanoceria signiﬁcantly decreased the area of ischemia-induced cell death in hippocampal slices. a Pseudocolor images of brain slices loaded with Sytox blue. b Quantiﬁcation of the area of Sytox fluorescence in mouse hippocampal slices after 30 min of ischemia and treatment with varying doses of nanoceria. Reprinted from Ref. [52], Copyright 2011, with permission from Elsevier

and weight, thus showing the translational promise of the nanoceria [61]. It was also reported that nanoceria could inhibit ovarian tumor growth via an anti-angiogenic mechanism [62]. Tissue engineering. Nanoceria has been used to promote (stem) cell proliferation and tissue engineering [64–68]. Traversa et al. prepared hybrid materials with enhanced mechanical properties by fabricating nanoceria together with PLGA scaffolds. They went on to demonstrate that the hybrids could promote the murine-derived cardiac and mesenchymal stem cells growth. Initially, the promotion effects of nanoceria were attributed to its antioxidation properties [64]. However, later they revealed that the cell proliferation was more favored on Ce4+ dominant regions rather than on Ce3+ dominant regions [65]. It suggested that Ce4+ dominant regions would promote the cell proliferation due to its hydrophilicity. On the other hand, Ce3+ dominant regions inhibited the cell proliferation by limiting

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4 Metal Oxide-Based Nanomaterials for Nanozymes

Fig. 4.4 Speciﬁc cell growth process on Ce4+and Ce3+ regions. Reprinted from Ref. [65], Copyright 2014, with permission from Elsevier

cell spreading and weakening the cell–material interactions (Fig. 4.4) [65]. This result was in agreement with other reports, which suggested that surface Ce3+ might be biotoxic [69]. Mattson, Seal, and co-workers demonstrated that nanoceria could accelerate cutaneous wound healing in mice by promoting the growth of keratinocytes, ﬁbroblasts, and vascular endothelial cells. The therapeutic efﬁcacy was owing to the enhanced proliferation and migration of these cells [66]. As shown in Fig. 4.5, when nanoceria (prepared in water) was used as additives, they could promote bone regeneration by enhancing collagen production from human mesenchymal stem cells. In comparison with the scaffolds themselves, osteoblast-like products were observed on the nanoceria-doped scaffolds even in the absence of osteogenic supplements. The promotion mechanism still remained unclear [67]. Anti-inflammation and antioxidation. Owing to the mixed valence and oxygen vacancy, nanoceria-based nanozymes exhibited anti-inflammation and antioxidation effects. Using J774A.1 murine macrophage cells, Reilly et al. demonstrated that nanoceria possessed anti-inflammatory activities. The nanoceria exhibited good biocompatibility after being internalized by the cells. Moreover, the nanoceria could both scavenge ROS and inhibit NO production, which in turn would inhibit inflammation [70]. In a mouse model with CCl4-induced liver injury, it was showed that the treatment with nanoceria mitigated systemic inflammation, reduced hepatic steatosis, and improved portal pressure. The anti-inflammatory effects of the nanoceria were also evidenced by the remarkable downregulation in mRNA expression of inflammatory cytokines, vasoconstrictor, oxidative stress messengers, etc. This study indicated that nanoceria might be used as a therapeutic drug for liver disease [71]. Nanoceria has also been widely used as antioxidants [41, 56, 72, 73]. Its antioxidizing activity was even better than that of commercial antioxidants such as Trolox [73]. Other applications. Nanoceria-based SOD mimics have been explored for other interesting applications [74, 75]. For instance, nanoceria showed antibacterial activities against Escherichia coli (a typical Gram-negative bacterium) and Bacillus subtilis (a typical Gram-positive bacterium) [74]. More interestingly, it showed that the nanoceria was ineffective against Shewanella oneidensis, which was not only a Gram-negative bacterium but also a metal-reducing bacterium. These studies indicated that the antibacterial activities of nanoceria were dependent not only on

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Fig. 4.5 SEM images of human mesenchymal stem cells cultured for 10 days on the bioactive glass scaffolds doped with nanoceria synthesized in water (a, b), in dextran (c, d) and without nanoceria (e, f). Cell culture was performed in the absence (a, c, e) and in the presence (b, d, f) of osteogenic supplements. Cells attached and spread on the scaffolds’ surface. Note the osteoblast-like products or minerals on the cells cultured in the absence (a, c, e) of osteogenic supplements (scale bar = 10 μm). Reprinted from Ref. [67], Copyright 2010, with permission from Royal Society of Chemistry

the nanozyme’s intrinsic properties (such as size, surface coating, etc.) but also on the bacterial species. Recently, nanoceria was integrated with a bioresorbable electronic stent [76]. During percutaneous coronary interventions, it might produce ROS and cause in-stent thrombosis due to the inflammation. To address these issues, nanoceria was used to not only scavenge ROS but also mitigate inflammation.

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Cerium Oxide as Catalase Mimics

Besides the SOD mimicking activities, the catalase-like activities of nanoceria have also been studied [77–80]. It was found that the oxidase mimicking activity of nanoceria was negatively correlated with the ratio of Ce3+/Ce4+, which was different from its SOD mimicking activity [78]. Detailed experimental and computational studies revealed that nanoceria could dismutate H2O2 into H2O and O2 via the mechanism shown in Eqs. 4.3–4.7 [79]. Such a mechanism was also consistent with a previously proposed one (Fig. 4.6) [39]. 2Ce3 þ þ H2 O2 þ 2H þ ! 2H2 O þ 2Ce4 þ

ð4:3Þ

H2 O2 þ Ce4 þ ! Ce3 þ þ 2H þ þ HOO

ð4:4Þ

Ce4 þ þ HOO ! Ce3 þ þ H þ þ O2

ð4:5Þ

H2 O2 þ 2Ce4 þ ! 2Ce3 þ þ 2H þ þ O2

ð4:6Þ

2H2 O2 ! 2H2 O þ O2

ð4:7Þ

Fig. 4.6 Proposed molecular mechanisms for the catalase mimicking activity of nanoceria. Reprinted from Ref. [39], Copyright 2011, with permission from Royal Society of Chemistry

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Traditional bioactive glasses with the composition of Na2O, CaO, SiO2, and P2O5 have been used for bone defect reparation. However, they cannot effectively prevent oxidative stress and reduce inflammation after implantation due to the inert chemistry. By introducing redox active nanomaterials, especially the ones with antioxidation and anti-inflammation activities, into the bioactive glasses would address this issue. To this end, nanoceria has been used to dope traditional bioactive glasses. The catalase mimicking activity of nanoceria-doped glasses was conﬁrmed by in vitro experiments and computational studies [79]. Liu et al. [77] developed an interesting strategy to fabricate biosensors for H2O2 and glucose. As shown in Fig. 4.7, the adsorption of dye-labeled DNA onto nanoceria quenched its fluorescence. The presence of H2O2 would displace

Fig. 4.7 a Sensing H2O2 by displacing adsorbed fluorescent DNA from nanoceria. The color of nanoceria is changed in the same process. b A proposed mechanism of H2O2-induced DNA release by capping the nanoceria surface. For the three time scales marked in the scheme, DNA release is related to the one on the order of 1 min. Adapted from Ref. [77], Copyright 2015, with permission from American Chemical Society

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adsorbed DNA from nanoceria and thus recover its fluorescence. The possible sensing mechanism was showed in Fig. 4.7b. The phosphate group of the DNA interacted with the Ce3+ on the nanoceria surface. H2O2, however, could compete against the bound DNA by oxidizing the Ce3+ into Ce4+ within one minute. The bound H2O2 would then be converted into H2O and O2 via a catalase-like mechanism. Moreover, when glucose oxidase (GOx) was coupled with the H2O2mediated DNA displacement from nanoceria, sensitive and selective glucose detection was achieved [77]. Using the same strategy, cellular H2O2 was detected with cerium oxide nanowires [80].

4.1.3

Cerium Oxide as Peroxidase Mimics

Nanoceria has been successfully used to mimic peroxidase [5, 81, 82]. The peroxidase mimicking activities were conﬁrmed by the fact that nanoceria could catalyze peroxidase’s substrates with H2O2. The detection of H2O2 and glucose has been achieved by making use of the nanoceria’s peroxidase-like activities [5]. Moreover, a sandwich immunoassay has been developed for detection of a breast cancer biomarker (i.e., CA15-3) [81]. The peroxidase-like nanoceria was attached to the detection antibody electrostatically, eliminating the time-consuming covalent bioconjugation procedure. Compared with the natural HRP-based sandwich assay, the nanozyme-based assay not only exhibited higher stability and lower cost but also had higher sensitivity (i.e., it had a detection limit one order of magnitude lower than that of HRP-based assay) [81].

4.1.4

Cerium Oxide as Oxidase Mimics

Perez et al. [83] reported the oxidase mimicking activity of polymer-coated nanoceria. Since no H2O2 was involved, the observed catalytic activity toward TMB oxidation at acidic conditions was attributed to the oxidase-like rather peroxidase-like properties of the nanoceria. The size-dependent study showed that smaller nanoceria exhibited higher oxidase mimicking activities. Moreover, the catalytic activities were also dependent on the surface coatings. The thinner and more permeable poly(acrylic acid)-coated nanoceria exhibited higher activity in comparison with the nanoceria coated with thicker dextran. Interestingly, when nanoceria was conjugated with folate, the obtained nanozyme probes were used for speciﬁc cancer cell detection (Fig. 4.8) [83]. The developed immunoassay was advantageous over traditional ELISA in the eliminating the use of unstable H2O2 and easily denatured HRP. The oxidase mimicking activities of nanoceria could be regulated by binding with ssDNA [84]. A colorimetric method for DNA detection has been reported by using the oxidase-like nanoceria. The detection was based on the target DNA induced shielding of the catalytic activity of nanozyme [85].

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Fig. 4.8 Comparison of traditional ELISA (a) and nanoceria-based ELISA (b). In traditional ELISA, an HRP antibody is utilized as secondary antibody that, upon hydrogen peroxide treatment, facilitates the oxidation of TMB, resulting in color development. In nanoceria-based ELISA, the oxidase-like activity of nanoceria facilitates the direct oxidation of TMB without the need of HRP or hydrogen peroxide. Reprinted from Ref. [83], Copyright 2009, with permission from John Wiley and Sons

4.1.5

Cerium Oxide as Other Mimics

Nanoceria has also been explored for mimicking other enzymes [18, 86, 87]. For example, nanoceria was able to eliminate nitric oxide radical. Unexpectedly, the nitric oxide radical scavenging activity of nanoceria was negatively correlated with the Ce3+/Ce4+ ratio, which was different from its SOD-like activity [86]. Kuchma et al. found that the nanoceria exhibited phosphatase-like activities. Nanoceria promoted the hydrolysis of phosphate ester bonds in p-nitrophenylphosphate (pNPP), o-phospho-L-tyrosine, ATP, but not in DNA. They showed that the phosphatase mimicking activity was dependent on the Ce3+ sites and oxygen vacancies. Facilitated with ﬁrst principles calculation, it was revealed that the catalysis proceeded via a SN2 mechanism (Fig. 4.9). Moreover, the activation energy for the hydrolysis was signiﬁcantly reduced when it was mediated by a Ce3 + -Ce3+ complex instead of a Ce4+-Ce4+ complex (from 22.9 to 13.6 kcal/mol). The lowered activation energy was attributed to the less polarized phosphorus-oxygen bonds in the phosphate-Ce3+-Ce3+ complex, which was purely electronic. It also suggested that the disfavored DNA hydrolysis with the nanoceria might be due to the steric hindrance, which could shield the interaction of phosphate bond with the Ce3+ sites [18].

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Fig. 4.9 The snapshots of the reaction pathway for pNPP hydrolysis catalyzed by nanoceria. a The reaction complex includes the neutral water molecule in the secondary coordination sphere. b The hydrogen bonding is switched to the bridging hydroxide anion. c The proton is transferred along this newly formed hydrogen bond. d The formed uncoordinated hydroxide then attacks pNPP and e forms the transition state. f The p-nitrophenyl anion then leaves, g deprotonates one of the water molecules in the ﬁrst coordination sphere, and h forms the hydrogen-bonded product complex. Reprinted from Ref. [18], Copyright 2010, with permission from Elsevier

4.2

Iron Oxide

Owing to their superior magnetic properties, iron oxide nanomaterials have been widely used in bioanalytical and biomedical ﬁelds for separation and capture of analytes, etc. Before Yan and co-workers’ surprising discovery, it was believed that these nanomaterials were chemically and biologically inert. Therefore, they were usually conjugated with various functional groups (such as metal catalysts, enzymes, or antibodies) for practical applications. In 2007, Yan et al. discovered the unexpected peroxidase mimicking activity of Fe3O4 magnetic nanoparticles (MNPs) [88]. Inspired by this seminal work, quite a lot of nanomaterials (including the iron oxide nanomaterials) have been explored to study their enzyme mimicking activities [6, 7, 89–115]. Most of iron oxide nanomaterials have showed intrinsic peroxidase mimicking activities though they could also mimic other natural enzymes. In this section, the enzyme mimetic properties of iron oxide nanomaterials and their applications are covered.

4.2.1

Iron Oxide as Peroxidase Mimics

(a) Catalytic activities and mechanisms Natural peroxidases catalyze the oxidation of its substrates with peroxide (H2O2 in most of case). They play important roles in biological systems. For example,

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Fig. 4.10 Fe3O4 MNPs performed as peroxidase mimics. a TEM images of employed Fe3O4 MNPs with different sizes. b The colorless peroxidase substrates TMB, DA and OPD were oxidized into their corresponding colored products in the presence of H2O2 via the catalysis of Fe3O4 MNPs. Reprinted from Ref. [88], Copyright 2007, with permission from Nature Publishing Group

glutathione (GSH) peroxidase can detoxify ROS while myeloperoxidase can defend against pathogens. Moreover, HRP is widely used in bioanalytical and biomedical research for amplifying detection signals, where it is conjugated to an antibody or other biorecognition molecules. In their pioneering study, Yan et al. showed that Fe3O4 MNPs could catalyze the oxidation of several peroxidase substrates with H2O2, suggesting that they possessed intrinsic peroxidase mimicking activities (Fig. 4.10) [88]. Compared with natural HRP, the nanozymes were unique in several aspects. First, they were more stable and could work in wider pH and temperature conditions. Second, they could be produced in large scale with low cost. Third, they could be conjugated with biorecognition (or other functional) elements due to the large surface area and rich surface chemistry. Fourth, they were multifunctional (i.e., they had both magnetic and catalytic properties) [88]. Fe3O4 MNPs with different sizes (30, 50 and 300 nm) were studied, showing that smaller nanoparticles had higher catalytic activity. Enzyme kinetics study revealed that the Fe3O4 MNPs mimicked reactions also followed a ping-pong mechanism (i.e., they exhibited parallel double-reciprocal plots of substrate concentration versus reaction rate) [88]. Interestingly, the nanozyme and HRP had Km values of 0.098 mM versus 0.434 mM for TMB, respectively, which indicated that the nanozyme showed even higher afﬁnity to TMB in comparison with HRP. On the other hand, the nanozyme exhibited lower afﬁnity to H2O2 compared with HRP [88]. The exact molecular mechanisms for the Fe3O4 MNPs mimicking peroxidase activities are still unclear. A few studies have suggested that Fenton and/or Haber– Weiss reaction mechanisms could be involved [116–118].

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(b) Applications Iron oxide nanomaterial-based nanozymes have been applied for many interesting applications, ranging from detection of H2O2 and glucose to immunoassay and immunostaining. H2O2 detection. Detection of H2O2 is very important because it plays critical roles in biology, medicine, environmental protection, food industry, etc. Wei and Wang have reported the ﬁrst example of H2O2 detection using Fe3O4 MNPs as the peroxidase mimic and ABTS as the colorimetric substrate (Fig. 4.11a) [119, 120]. The presence of H2O2 could be easily visualized by the colored product of ABTSox (i.e., oxidized ABTS∙+). Moreover, the amount of H2O2 could be quantiﬁed by measuring the corresponding absorption spectra [119]. Since then, considerable studies have been devoted to the H2O2 detection using peroxidase-like nanozymes (see Table A.1) [6, 7].

Fig. 4.11 a Nanozyme as peroxidase mimic for colorimetric sensing of H2O2, and glucose when combined with glucose oxidase. b The sensing format in (a) could be extended to other targets (substrate 1 here) when combined with a suitable oxidase. c Target of interest as substrate 0 could be determined if it could be converted into an oxidase substrate. Numerous transduction signals can be adopted for sensing (such as colorimetric, fluorometric, chemiluminescent, and SERS signals when the corresponding substrates are used; and electrochemical signals when a nanozyme is immobilized on an electrode). Reprinted from Ref. [7], Copyright 2016, with permission from Royal Society of Chemistry

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Glucose (and other oxidase substrate) detection. Wei and Wang [119] went on to demonstrate that glucose detection could be achieved by coupling GOx with a peroxidase-like nanozyme. As shown in Fig. 4.11a, GOx ﬁrst converted glucose to H2O2, which subsequently oxidized a substrate into the corresponding product (such as colored ABTS∙+ here). The established method showed excellent sensitivity and selectivity toward glucose detection (Fig. 4.12) [119]. Followed by this work, others have used other nanomaterials-based peroxidase mimics to detect glucose even in complicated samples (such as in serum, urine, drinks, etc.) (see Table A.2 for more examples) [6, 7]. As indicated in Fig. 4.11b, when other oxidases were used, the corresponding oxidase substrates could be detected [6, 7]. Numerous biological important small molecules, such as choline, uric acid, D-alanine, lactate, and xanthine, have been detected with the proposed sensing method (see Table A.2 for more examples) [6, 7]. As indicated in Fig. 4.11c, the analytes as substrate 0 could also be detected by converting them to oxidase substrates [6, 7]. Moreover, the proposed sensing strategy could also be used to screen enzyme inhibitors. For example, Yan et al. [121] reported a rapid and sensitive method for detecting organophosphorus pesticides and nerve agents (such as Sarin), which were high potent acetylcholinesterase inhibitors. DNA detection. Two possible approaches are available for DNA detection by using the peroxidase mimicking activities of iron oxide nanomaterials. First, it has been established that ssDNA and dsDNA exhibited different afﬁnities toward the

Fig. 4.12 Colorimetric detection of glucose by combining GOx with Fe3O4 MNPs as a peroxidase mimic. Reprinted from Ref. [119], Copyright 2008, with permission from American Chemical Society

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nanozymes. A probe ssDNA would adsorb onto a nanozyme and thus shield its activity. The presence of a target ssDNA would form a duplex with the probe ssDNA, which would subsequently recover the nanozyme’s activity. For instance, Park et al. reported the detection of Chlamydia trachomatis pathogen DNA from a human urine sample via such a sensing strategy [122]. Second, by using a nanozyme as an alternative to conventional dyes (or enzymes) to label a probe ssDNA, the target DNA could be detected via by hybridizing the probe ssDNA and target ssDNA. Many sensing platforms could be adopted for this purpose. For example, in a sandwich assay, a capture ssDNA would ﬁrst interact with a target ssDNA. Then a nanozyme labeled probe ssDNA would further interact with the captured target ssDNA for signaling [123]. Liu et al. [124] found that in certain cases, DNA could even accelerate the peroxidase mimicking activities of Fe3O4 MNPs. It was speculated that the enhancement might be due to the electrostatic interaction between negatively charged DNA and positively charged TMB substrate. Immunoassay. In Yan’s initial report, they developed two immunoassay formats [88]. Using an antigen-down immunoassay format, the detection of hepatitis B virus surface antigen (preS1) was achieved. In a second demonstration, a capturedetection sandwich immunoassay format was used for the detection of the myocardial infarction biomarker troponin I (TnI) [88]. Yan and co-workers recently developed a nanozyme-strip for Ebola detection by integrating lateral flow technique with the Fe3O4 MNPs nanozyme (Fig. 4.13) [125]. AuNPs are commonly used to fabricate lateral flow strips, but their sensitivity should be further improved to meet the requirements for infectious diseases (such as Ebola) diagnosis and monitoring. To tackle this challenge, Yan et al. used Fe3O4 MNPs nanozyme to replace AuNPs for fabricating the nanozyme-strips. Compared with the AuNPs-based strip, the nanozyme exhibited 100-fold better sensitivity toward the detection of Ebola virus glycoprotein (EBOV-GP) (Fig. 4.13c–e). The enhanced sensitivity could be attributed to the high catalytic activity of the nanozymes. Moreover, the nanozyme-strip showed comparable analytical performance with ELISA. Due to high sensitivity, low fabrication cost, and ease of use, the nanozyme-strip would ﬁnd applications in ﬁghting against emergent virus diseases, especially in resource limited areas [125]. Other important targets, such as carcinoembryonic antigen (CEA), has been detected by using Fe3O4 MNPs-based peroxidase mimics (see Table A.3 for more examples) [126]. Cancer cells have also been selectively detected when the nanozymes were labeled with speciﬁc biorecognition elements (such as folic acid) [127]. Immunostaining. Yan et al. [99] also developed nanozymes for speciﬁc tumor tissue imaging (Fig. 4.14). The probe was prepared by encapsulating catalytic iron oxide nanoparticles within recombinant human heavy-chain ferritin shells to get magnetoferritin nanoparticles. The magnetoferritin nanoparticles exhibited peroxidase mimicking activity. When they were used for staining tumor tissues, they

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Fig. 4.13 a Standard AuNPs-based strip, b nanozyme-strip employing Fe3O4 MNPs in place of AuNPs, c nanozyme-strip, d standard colloidal gold strip and e ELISA method for EBOV-GP detection. The asterisk (*) indicates the limit of visual detection of the test line in strips.# OD450 nm > cut-off value. Reprinted from Ref. [125], Copyright 2015, with permission from Elsevier

would differentiate tumor tissues from the benign ones due to the speciﬁc interactions between ferritin and the overexpressed transferrin receptor 1 onto tumor tissues. Very encouragingly, for the 474 patient specimens stained, the magnetoferritin nanoparticles distinguished cancer samples from normal ones with a remarkable success (i.e., with a sensitivity of 98 % and a speciﬁcity of 95 %). Gu and co-workers also showed that iron oxide nanoparticles-based nanozymes could be used for immunohistochemical studies [94]. Aptasensors. Several studies have demonstrated that aptasensors could be developed by combining the speciﬁc recognition capability of aptamers and the

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Fig. 4.14 Magnetoferritin nanoparticles as peroxidase mimic for tumor tissue staining and imaging. a Preparation of magnetoferritin nanoparticles. b Magnetoferritin nanoparticle staining of tumor tissues. Reprinted from Ref. [99], Copyright 2012, with permission from Nature Publishing Group

high catalytic activities of iron oxide-based nanozymes [128–130]. For instance, Yang et al. [128] reported an aptasensor for thrombin. It is well known that thrombin has two speciﬁc binding aptamers, one is a 15-mer and the other is a 29-mer. The two aptamers bind to the different sites onto a thrombin and thus would form a sandwich structure. Based on such speciﬁc interaction, the 29-mer aptamer was used to capture thrombin while the 15-mer aptamer was used to label iron oxide nanoparticles. The presence of thrombin would form a sandwich structure, and the 15-mer aptamer labeled iron oxide nanoparticles would catalyze the oxidation of TMB for signaling [128]. Zhu, Wang, and co-workers [129] developed a peroxidase mimic based on hybrid nanostructures (Fig. 4.15a). The nanozyme had a Fe3O4 core, coated with Ag–Pd nanocages. Electrochemical measurements demonstrated that the hybrid nanostructures had higher catalytic activity than Fe3O4 alone. They then developed an aptasensor for CTCs (circulating tumor cells)

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Fig. 4.15 a Schematic illustration of the fabrication of Fe3O4@Ag–Pd nanozymes. b Schematic illustration of CTCs detection. c DPV responses to different concentrations of MCF-7 cells. d DPV responses to various types of cells. Reprinted from Ref. [129], Copyright 2014, with permission from American Chemical Society

detection. SYL3C aptamer, which speciﬁcally interact with overexpressed epithelial cell adhesion molecule (EpCAM) on CTCs, was used to capture the CTCs and to label the hybrid nanostructures (Fig. 4.15b). As shown in Fig. 4.15c, d, the developed aptasensor showed good sensitivity and selectivity toward CTCs detection [129].

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4 Metal Oxide-Based Nanomaterials for Nanozymes

Iron Oxide as Other Enzyme Mimics

Iron oxide nanoparticles have been used to mimic catalase as well as other enzymes [108, 131–135]. For instance, Gu and co-workers [131] found that iron oxide nanoparticles exhibited dual enzyme-like activities. For both Fe3O4 and γ-Fe2O3 nanoparticles, they showed peroxidase-like and catalase-like activities at acidic and neutral conditions, respectively. It was found that both the peroxidase and catalase mimicking activities of Fe3O4 nanoparticles were higher than that of γ-Fe2O3 nanoparticles. The cellular studies revealed that the iron oxide nanoparticles exhibited concentration-dependent cytotoxicity to human glioma U251 cells. The cytotoxicity was attributed to the nanoparticles’ peroxidase-like activities within acidic lysosomes, which would trap the nanoparticles to catalytically produce hydroxyl radicals (Fig. 4.16). It also suggested that γ-Fe2O3 would be safer for biomedical applications [131]. In a subsequent study, Gu and co-workers [133] went on to use Fe2O3 nanoparticles to protect hearts from ischemic damage both in vitro and in vivo (Fig. 4.17a). It revealed that the protective activity was mainly from the nanoparticles themselves rather than the surface coatings. Ischemic injury is mediated via complicated mechanisms. Therefore, comprehensive studies were carried out, which suggested that the Fe2O3 nanoparticles would exert their protection effects via several mechanisms. First, they could inhibit the cellular ROS-induced membrane lipid peroxidation. Second, they could attenuate Ca2+ influx, which in turn

Fig. 4.16 Schematic illustration of peroxidase-like activity-induced cytotoxicity by iron oxide nanoparticles. The nanoparticles are trapped in acidic lysosomes when internalized into cells, so they catalyze H2O2 to produce hydroxyl radicals through peroxidase-like activity; however, in neutral cytosol, the nanoparticles would decompose H2O2 through catalase-like activity. Reprinted from Ref. [131], Copyright 2012, with permission from American Chemical Society

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Fig. 4.17 a Cardioprotective activity of Fe2O3 nanoparticles. b Effects of dietary Fe3O4 nanoparticles in a Drosophila Alzheimer’s Disease model. a Reprinted from Ref. [133], Copyright 2015, with permission from Nature Publishing Group. b Reprinted from Ref. [132], Copyright 2016, with permission from John Wiley and Sons

inhibited ROS. Third, they could increase NO production by promoting NO producing proteins’ activities and enhance NO protective effects by increasing the level of S-nitrosothiols. More convincing investigations are needed to completely understand the protective roles of the Fe2O3 nanoparticles [108]. Nevertheless, since the nanoparticles did not show obvious toxicity toward normal cardiomyocytes and they were more potent than Verapamil (a synthetic drug) and Salvia miltiorrhiza extract (a natural antioxidant), they were expected to be further explored as potential nanomedicine for cardiovascular diseases treatment [133]. The protective effects of iron oxide nanoparticles against ischemic brain injury were also reported [134]. Dietary Fe3O4 nanoparticles have been used to treat Drosophila with Alzheimer’s Disease (Fig. 4.17b) [132]. It was demonstrated that the Fe3O4 nanoparticles could mimic catalase in vivo. Therefore, they would improve neurodegeneration in a Drosophila Alzheimer’s Disease model by reducing intracellular oxidative stress [132]. This study together with others indicated that iron oxide nanoparticles-based nanozymes may help to treat diseases associated with oxidative stress.

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4.3

4 Metal Oxide-Based Nanomaterials for Nanozymes

Other Metal Oxides

Many other metal oxides have been explored to mimic natural enzymes [35, 136–149].

4.3.1

Vanadium Oxide as Enzyme Mimics

Vanadium oxide nanomaterials (such as V2O5 and V2O3) have been used to mimic natural enzymes for biosensing, antibiofouling, cytoprotection, etc. [136–139, 150]. Tremel et al. [136] showed that V2O5 nanowires possessed intrinsic peroxidase mimicking activity. In a subsequent study, they demonstrated that the V2O5 nanowires mimicked natural vanadium haloperoxidase (Fig. 4.18) [137]. A potential mechanism for the vanadium haloperoxidase mimicking activity was showed in Fig. 4.18b. Interestingly, it has been demonstrated that the nanozymes could be used to prevent marine biofouling (Fig. 4.18c–f) [137]. Mugesh, D’Silva, and co-workers [138] showed that V2O5 nanowires could also mimic GSH peroxidase, an important cellular antioxidation enzyme (Fig. 4.19). By using intracellular glutathione, the nanozyme could protect cells from both intrinsic and external oxidative injuries. Moreover, the nanozyme has successfully restored the ROS balance without disturbing the cell’s own antioxidation defense systems. As shown in Fig. 4.19, a possible mechanism was proposed. H2O2 could be adsorbed onto the nanozyme and was then reduced into H2O, leading to the formation of complex 1. Complex 1 then interacted with GSH and formed complex 2, which would be hydrolyzed into complexes 3 and 4. The reaction of complex 4 with H2O2 would regenerate complex 1. It should be noted that complex 3 could be converted to GSSG, which was further transformed to GSH by glutathione reductase (GR) and NADPH [138]. DNA and glucose detection has been reported by using polydopamine-coated V2O5 nanowires as peroxidase mimics [151]. In another report, V2O3-loaded mesoporous carbon has been used for colorimetric detection of glucose by using its peroxidase mimicking activity [139].

4.3.2

Cobalt Oxide as Enzyme Mimics

Several reports have showed that cobalt oxide (especially Co3O4) nanomaterials could mimic peroxidase, catalase, SOD, etc. [150, 152, 153]. For example, Wang et al. [152] reported the catalase-like activity of Co3O4 nanoparticles. It was proposed that the catalysis could be mediated via a Co2+ → Co3+ → Co2+ regeneration mechanism. In a following study, they demonstrated that the Co3O4 nanoparticles’ catalase mimicking activities could be modulated by controlling the

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79

Fig. 4.18 a TEM image of V2O5 nanowires. b Proposed mechanism for V2O5 nanowires’ vanadium haloperoxidase mimicking activity. c–f Effect of V2O5 nanowires on marine biofouling. Digital image of a stainless steel plate (2 × 2 cm) covered with a commercially available paint for boat hulls without and with V2O5 nanowires. The plates were ﬁxed to a boat hull. c, d Immediately after ﬁxation, both stainless steel plates (with and without V2O5 nanowires) had clean surfaces. The boat was kept in seawater (lagoon with tidal water directly connected to the Atlantic Ocean). After 60 days, the boat was taken from the water. e The painted stainless steel plates without V2O5 nanowires suffered from severe natural biofouling. f Plates with V2O5 nanowires showed a complete absence of biofouling. Adapted from Ref. [137], Copyright 2012, with permission from Nature Publishing Group

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Fig. 4.19 Proposed molecular mechanism for V2O5 nanowires’ GSH peroxidase mimicking activity. Reprinted from Ref. [138], Copyright 2014, with permission from Nature Publishing Group

nanoparticles’ morphologies. The nanozymes exhibited different activities in the order of nanoplates > nanorods > nanocubes. Moreover, they discovered that the nanozymes’ activities could be speciﬁcally enhanced by Ca2+. Based on this phenomenon, they constructed a biosensor for Ca2+. With the biosensor, spiked Ca2+ in milk was successfully determined [154]. Zhang, Gu, and co-workers [150] found that the Co3O4 nanoparticles possessed multiple enzyme-like activities (i.e., catalase-like, peroxidase-like, and SOD-like activities). For all the three mimics, the Co2+ → Co3+ → Co2+ regeneration mechanism was involved. Compared with Fe3O4 nanoparticles, Co3O4 nanoparticles exhibited higher enzyme mimicking activities. After establishing the enzyme mimicking activities, they developed an immunoassay for vascular endothelial growth factor (VEGF) detection [150].

4.3 Other Metal Oxides

4.3.3

81

Copper Oxide as Enzyme Mimics

Chen’s and others’ groups have reported the enzyme mimicking activities of copper oxide nanomaterials [147, 155–164]. For instance, Chen et al. demonstrated that CuO nanoparticles with an average size of 30 nm exhibited peroxidase mimicking activity [155]. Enzyme kinetics study revealed that the CuO-based nanozyme had higher afﬁnity toward TMB than natural HRP and several other nanozymes (e.g., Fe3O4- and FeS-based peroxidase mimics). By combining the CuO nanozyme with cholesterol oxidase, they have developed a chemiluminescent biosensor for cholesterol detection [164]. Glucose and lactate detection was also reported by using CuO nanoparticles as peroxidase mimics [156].

4.3.4

MoO3, TiO2, MnO2, RuO2 as Enzyme Mimics

Tremel et al. [149] studied the enzyme mimicking activities of MoO3 nanoparticles and found that they could mimic sulﬁte oxidase, which catalyzed the oxidation of sulﬁte to sulfate. After establishing the sulﬁte oxidase mimicking activity in vitro, they further demonstrated that the nanozyme could work in living cells and recovered the sulﬁte oxidase activity in sulﬁte oxidase knockdown cells [149]. In this case, the intracellular sulﬁte oxidase activity was chemically inhibited by sodium tungstate treatment. Since native sulﬁte oxidase is localized within mitochondria, the nanozyme was conjugated with triphenylphosphonium moieties for mitochondria targeting. When the sulﬁte oxidase deﬁcient cells were treated with the nanozymes, their sulﬁte oxidase activity was restored [149]. Dong et al. fabricated TiO2 nanotube arrays via a potentiostatic anodization strategy. They further showed that the TiO2 nanotube arrays exhibited peroxidase-like activity. Sensitive detection of H2O2 was demonstrated by using the TiO2 nanotube arrays as a working electrode, which showed catalytic activity toward H2O2 reduction. Moreover, when GOx was immobilized onto the TiO2 nanotube arrays, an electrochemical sensor for glucose detection was obtained. As shown in Fig. 4.20, the biosensor exhibited excellent sensitivity and selectivity toward glucose determination. Besides, the biosensor was further used to measure the glucose concentrations in diabetes patients, showing satisfactory performance [148]. Gao et al. [140] have constructed an electrochemical DNA biosensor by using the peroxidase mimicking activity of RuO2 nanoparticles. When the RuO2 nanoparticles labeled probe ssDNA was speciﬁcally assembled onto an electrode in a sandwich manner with the capture ssDNA and target ssDNA, the nanoparticles catalyzed the deposition of polyaniline and produced catalytic electrochemical signals for detection. Zhang and co-workers demonstrated that MnO2 nanowires were excellent peroxidase mimics. They then developed an immunoassay to detect sulfate-reducing bacteria [144].

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Fig. 4.20 a Cyclic voltammograms (CVs) obtained at the GOx/TiO2 nanotube array electrode in 0.1 M pH 5.5 PBS without (a) and with (b) 4 mM glucose. b CVs obtained at the TiO2 nanotube array electrode in 0.1 M pH 5.5 PBS without (a) and with (b) 4 mM glucose. c Amperometric response obtained at the GOD/TiO2 nanotube array electrode in 0.1 M pH 5.5 PBS upon successive injection of 0.2 mM glucose for each step at −0.35 V, the inset is the linear ﬁtted current plot to glucose concentration. d Amperometric response at the GOD/TiO2 nanotube array electrode in 0.1 M pH 5.5 PBS at −0.35 V with sequential injection of 1 mM glucose (a), 2 mM fructose (b), 2 mM lactose (c), 2 mM sucrose (d), 2 mM maltose (e), and 1 mM glucose (f). Reprinted from Ref. [148], Copyright 2013, with permission from Royal Society of Chemistry

References 1. Esch, F., Fabris, S., Zhou, L., Montini, T., Africh, C., Fornasiero, P., et al. (2005). Electron localization determines defect formation on ceria substrates. Science, 309, 752–755. 2. Karakoti, A., Singh, S., Dowding, J. M., Seal, S., & Self, W. T. (2010). Redox-active radical scavenging nanomaterials. Chemical Society Reviews, 39, 4422–4432. 3. Grulke, E., Reed, K., Beck, M., Huang, X., Cormack, A., & Seal, S. (2014). Nanoceria: Factors affecting its pro- and anti-oxidant properties. Environmental Science-Nano, 1, 429–444. 4. Kumar, A., Das, S., Munusamy, P., Self, W., Baer, D. R., Sayle, D. C., et al. (2014). Behavior of nanoceria in biologically-relevant environments. Environmental Science-Nano, 1, 516–532. 5. Zhao, H., Dong, Y. M., Jiang, P. P., Wang, G. L., & Zhang, J. J. (2015). Highly dispersed CeO2 on TiO2 nanotube: A synergistic nanocomposite with superior peroxidase-like activity. ACS Applied Materials & Interfaces, 7, 6451–6461.

References

83

6. Wei, H., & Wang, E. K. (2013). Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artiﬁcial enzymes. Chemical Society Reviews, 42, 6060–6093. 7. Wang, X. Y., Hu, Y. H., & Wei, H. (2016). Nanozymes in bionanotechnology: From sensing to therapeutics and beyond. Inorganic Chemistry Frontiers, 3, 41–60. 8. Xu, C., & Qu, X. G. (2014). Cerium oxide nanoparticle: A remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6, e60. 9. Tarnuzzer, R. W., Colon, J., Patil, S., & Seal, S. (2005). Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Letters, 5, 2573–2577. 10. Karakoti, A. S., Singh, S., Kumar, A., Malinska, M., Kuchibhatla, S., Wozniak, K., et al. (2009). PEGylated nanoceria as radical scavenger with tunable redox chemistry. Journal of the American Chemical Society, 131, 14144–14145. 11. Liu, X. Y., Wei, W., Yuan, Q., Zhang, X., Li, N., Du, Y. G., et al. (2012). Apoferritin-CeO2 nano-truffle that has excellent artiﬁcial redox enzyme activity. Chemical Communications, 48, 3155–3157. 12. Singh, S., Dosani, T., Karakoti, A. S., Kumar, A., Seal, S., & Self, W. T. (2011). A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials, 32, 6745–6753. 13. Kamada, K., & Soh, N. (2015). Enzyme-mimetic activity of Ce-intercalated titanate nanosheets. Journal of Physical Chemistry B, 119, 5309–5314. 14. McCormack, R. N., Mendez, P., Barkam, S., Neal, C. J., Das, S., & Seal, S. (2014). Inhibition of nanoceria’s catalytic activity due to Ce3+ site-speciﬁc interaction with phosphate ions. Journal of Physical Chemistry C, 118, 18992–19006. 15. Cafun, J.-D., Kvashnina, K. O., Casals, E., Puntes, V. F., & Glatzel, P. (2013). Absence of Ce3+ sites in chemically active colloidal ceria nanoparticles. ACS Nano, 7, 10726–10732. 16. Babu, S., Cho, J. H., Dowding, J. M., Heckert, E., Komanski, C., Das, S., et al. (2010). Multicolored redox active upconverter cerium oxide nanoparticle for bio-imaging and therapeutics. Chemical Communications, 46, 6915–6917. 17. Madero-Visbal, R. A., Alvarado, B. E., Colon, J. F., Baker, C. H., Wason, M. S., Isley, B., et al. (2012). Harnessing nanoparticles to improve toxicity after head and neck radiation. Nanomedicine-Nanotechnology Biology and Medicine, 8, 1223–1231. 18. Kuchma, M. H., Komanski, C. B., Colon, J., Teblum, A., Masunov, A. E., Alvarado, B., et al. (2010). Phosphate ester hydrolysis of biologically relevant molecules by cerium oxide nanoparticles. Nanomedicine-Nanotechnology Biology and Medicine, 6, 738–744. 19. Colon, J., Hsieh, N., Ferguson, A., Kupelian, P., Seal, S., Jenkins, D. W., et al. (2010). Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomedicine-Nanotechnology Biology and Medicine, 6, 698–705. 20. Hayat, A., Bulbul, G., & Andreescu, S. (2014). Probing phosphatase activity using redox active nanoparticles: A novel colorimetric approach for the detection of enzyme activity. Biosensors & Bioelectronics, 56, 334–339. 21. Oezel, R. E., Alkasir, R. S. J., Ray, K., Wallace, K. N., & Andreescu, S. (2013). Comparative evaluation of intestinal nitric oxide in embryonic zebraﬁsh exposed to metal oxide nanoparticles. Small (Weinheim an der Bergstrasse, Germany), 9, 4250–4261. 22. Tsai, Y.-Y., Oca-Cossio, J., Lin, S.-M., Woan, K., Yu, P.-C., & Sigmund, W. (2008). Reactive oxygen species scavenging properties of ZrO2-CeO2 solid solution nanoparticles. Nanomedicine, 3, 637–645. 23. Das, S., Dowding, J. M., Klump, K. E., McGinnis, J. F., Self, W., & Seal, S. (2013). Cerium oxide nanoparticles: applications and prospects in nanomedicine. Nanomedicine, 8, 1483–1508. 24. Karakoti, A. S., Monteiro-Riviere, N. A., Aggarwal, R., Davis, J. P., Narayan, R. J., Self, W. T., et al. (2008). Nanoceria as antioxidant: Synthesis and biomedical applications. Journal of the Minerals Metals and Materials Society, 60, 33–37.

84

4 Metal Oxide-Based Nanomaterials for Nanozymes

25. Bhushan, B., & Gopinath, P. (2015). Antioxidant nanozyme: A facile synthesis and evaluation of the reactive oxygen species scavenging potential of nanoceria encapsulated albumin nanoparticles. Journal of Materials Chemistry B, 3, 4843–4852. 26. Li, M., Shi, P., Xu, C., Ren, J., & Qu, X. (2013). Cerium oxide caged metal chelator: Anti-aggregation and anti-oxidation integrated H2O2-responsive controlled drug release for potential Alzheimer’s disease treatment. Chemical Science, 4, 2536–2542. 27. Li, H., Yang, Z.-Y., Liu, C., Zeng, Y.-P., Hao, Y.-H., Gu, Y., et al. (2015). PEGylated ceria nanoparticles used for radioprotection on human liver cells under gamma-ray irradiation. Free Radical Biology and Medicine, 87, 26–35. 28. Muhammad, F., Wang, A., Qi, W., Zhang, S., & Zhu, G. (2014). Intracellular antioxidants dissolve man-made antioxidant nanoparticles: Using redox vulnerability of nanoceria to develop a responsive drug delivery system. ACS Applied Materials & Interfaces, 6, 19424–19433. 29. Weaver, J. D., & Stabler, C. L. (2015). Antioxidant cerium oxide nanoparticle hydrogels for cellular encapsulation. Acta Biomaterialia, 16, 136–144. 30. Xu, C., Liu, Z., Wu, L., Ren, J., & Qu, X. (2014). Nucleoside triphosphates as promoters to enhance nanoceria enzyme-like activity and for single-nucleotide polymorphism typing. Advanced Functional Materials, 24, 1624–1630. 31. Xu, C., Lin, Y., Wang, J., Wu, L., Wei, W., Ren, J., et al. (2013). Nanoceria-triggered synergetic drug release based on CeO2-capped mesoporous silica host-guest interactions and switchable enzymatic activity and cellular effects of CeO2. Advanced Healthcare Materials, 2, 1591–1599. 32. Patil, S., Sandberg, A., Heckert, E., Self, W., & Seal, S. (2007). Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. Biomaterials, 28, 4600–4607. 33. Xue, Y., Luan, Q., Yang, D., Yao, X., & Zhou, K. (2011). Direct evidence for hydroxyl radical scavenging activity of cerium oxide nanoparticles. Journal of Physical Chemistry C, 115, 4433–4438. 34. Barkam, S., Das, S., Saraf, S., McCormack, R., Richardson, D., Atencio, L., et al. (2015). The change in antioxidant properties of dextran-coated redox active nanoparticles due to synergetic photoreduction-oxidation. Chemistry-A European Journal, 21, 12646–12656. 35. Schubert, D., Dargusch, R., Raitano, J., & Chan, S. W. (2006). Cerium and yttrium oxide nanoparticles are neuroprotective. Biochemical and Biophysical Research Communications, 342, 86–91. 36. Korsvik, C., Patil, S., Seal, S., & Self, W. T. (2007). Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chemical Communications, 1056–1058. 37. Heckert, E. G., Karakoti, A. S., Seal, S., & Self, W. T. (2008). The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials, 29, 2705–2709. 38. Sardesai, N. P., Andreescu, D., & Andreescu, S. (2013). Electroanalytical evaluation of antioxidant activity of cerium oxide nanoparticles by nanoparticle collisions at microelectrodes. Journal of the American Chemical Society, 135, 16770–16773. 39. Celardo, I., Pedersen, J. Z., Traversa, E., & Ghibelli, L. (2011). Pharmacological potential of cerium oxide nanoparticles. Nanoscale, 3, 1411–1420. 40. Li, Y., He, X., Yin, J.-J., Ma, Y., Zhang, P., Li, J., et al. (2015). Acquired superoxide-scavenging ability of ceria nanoparticles. Angewandte Chemie-International Edition, 54, 1832–1835. 41. Celardo, I., De Nicola, M., Mandoli, C., Pedersen, J. Z., Traversa, E., & Ghibelli, L. (2011). Ce3+ ions determine redox-dependent anti-apoptotic effect of cerium oxide nanoparticles. ACS Nano, 5, 4537–4549. 42. Fernandez-Garcia, S., Jiang, L., Tinoco, M., Hungria, A. B., Han, J., Blanco, G., et al. (2016). Enhanced hydroxyl radical scavenging activity by doping lanthanum in ceria nanocubes. Journal of Physical Chemistry C, 120, 1891–1901.

References

85

43. Zhu, A. P., Sun, K., & Petty, H. R. (2012). Titanium doping reduces superoxide dismutase activity, but not oxidase activity, of catalytic CeO2 nanoparticles. Inorganic Chemistry Communications, 15, 235–237. 44. Lin, Y., Xu, C., Ren, J., & Qu, X. (2012). Using thermally regenerable cerium oxide nanoparticles in biocomputing to perform label-free, resettable, and colorimetric logic operations. Angewandte Chemie-International Edition, 51, 12579–12583. 45. Lord, M. S., Jung, M., Teoh, W. Y., Gunawan, C., Vassie, J. A., Amal, R., et al. (2012). Cellular uptake and reactive oxygen species modulation of cerium oxide nanoparticles in human monocyte cell line U937. Biomaterials, 33, 7915–7924. 46. Selvaraj, V., Nepal, N., Rogers, S., Manne, N. D. P. K., Arvapalli, R., Rice, K. M., et al. (2015). Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles. Biomaterials, 59, 160–171. 47. Chen, J. P., Patil, S., Seal, S., & McGinnis, J. F. (2006). Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nature Nanotechnology, 1, 142–150. 48. Cai, X., Sezate, S. A., Seal, S., & McGinnis, J. F. (2012). Sustained protection against photoreceptor degeneration in tubby mice by intravitreal injection of nanoceria. Biomaterials, 33, 8771–8781. 49. Cai, X., Seal, S., & McGinnis, J. F. (2014). Sustained inhibition of neovascularization in vldlr–/– mice following intravitreal injection of cerium oxide nanoparticles and the role of the ASK1-P38/JNK-NF-kappa B pathway. Biomaterials, 35, 249–258. 50. Wong, L. L., Pye, Q. N., Chen, L., Seal, S., & McGinnis, J. F. (2015). Deﬁning the catalytic activity of nanoceria in the p23h-1 rat, a photoreceptor degeneration model. PLoS ONE, 10, e0121977. 51. Das, M., Patil, S., Bhargava, N., Kang, J. F., Riedel, L. M., Seal, S., et al. (2007). Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials, 28, 1918–1925. 52. Estevez, A. Y., Pritchard, S., Harper, K., Aston, J. W., Lynch, A., Lucky, J. J., et al. (2011). Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radical Biology and Medicine, 51, 1155–1163. 53. Kim, C. K., Kim, T., Choi, I.-Y., Soh, M., Kim, D., Kim, Y.-J., et al. (2012). Ceria nanoparticles that can protect against ischemic stroke. Angewandte Chemie-International Edition, 51, 11039–11043. 54. Heckman, K. L., DeCoteau, W., Estevez, A., Reed, K. J., Costanzo, W., Sanford, D., et al. (2013). Custom cerium oxide nanoparticles protect against a free radical mediated autoimmune degenerative disease in the brain. ACS Nano, 7, 10582–10596. 55. Kwon, H. J., Cha, M.-Y., Kim, D., Kim, D. K., Soh, M., Shin, K., et al. (2016). Mitochondria-targeting ceria nanoparticles as antioxidants for alzheimer’s disease. ACS Nano, 10, 2860–2870. 56. Pagliari, F., Mandoli, C., Forte, G., Magnani, E., Pagliari, S., Nardone, G., et al. (2012). Cerium oxide nanoparticles protect cardiac progenitor cells from oxidative stress. ACS Nano, 6, 3767–3775. 57. Niu, J., Azfer, A., Rogers, L. M., Wang, X., & Kolattukudy, P. E. (2007). Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovascular Research, 73, 549–559. 58. Kolli, M. B., Manne, N. D. P. K., Para, R., Nalabotu, S. K., Nandyala, G., Shokuhfar, T., et al. (2014). Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension. Biomaterials, 35, 9951–9962. 59. Niu, J. L., Azfer, A., Rogers, L. M., Wang, X. H., & Kolattukudy, P. E. (2007). Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovascular Research, 73, 549–559. 60. Alili, L., Sack, M., Karakoti, A. S., Teuber, S., Puschmann, K., Hirst, S. M., et al. (2011). Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor-stroma interactions. Biomaterials, 32, 2918–2929.

86

4 Metal Oxide-Based Nanomaterials for Nanozymes

61. Alili, L., Sack, M., von Montfort, C., Giri, S., Das, S., Carroll, K. S., et al. (2013). Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxidants & Redox Signaling, 19, 765–778. 62. Giri, S., Karakoti, A., Graham, R. P., Maguire, J. L., Reilly, C. M., Seal, S., et al. (2013). Nanoceria: A rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer. PLoS ONE, 8, e54578. 63. Alpaslan, E., Yazici, H., Golshan, N. H., Ziemer, K. S., & Webster, T. J. (2015). pH-dependent activity of dextran-coated cerium oxide nanoparticles on prohibiting osteosarcoma cell proliferation. ACS Biomaterials-Science & Engineering, 1, 1096–1103. 64. Mandoli, C., Pagliari, F., Pagliari, S., Forte, G., Di Nardo, P., Licoccia, S., et al. (2010). Stem cell aligned growth induced by CeO2 nanoparticles in PLGA scaffolds with improved bioactivity for regenerative medicine. Advanced Functional Materials, 20, 1617–1624. 65. Naganuma, T., & Traversa, E. (2014). The effect of cerium valence states at cerium oxide nanoparticle surfaces on cell proliferation. Biomaterials, 35, 4441–4453. 66. Chigurupati, S., Mughal, M. R., Okun, E., Das, S., Kumar, A., McCaffery, M., et al. (2013). Effects of cerium oxide nanoparticles on the growth of keratinocytes, ﬁbroblasts and vascular endothelial cells in cutaneous wound healing. Biomaterials, 34, 2194–2201. 67. Karakoti, A. S., Tsigkou, O., Yue, S., Lee, P. D., Stevens, M. M., Jones, J. R., et al. (2010). Rare earth oxides as nanoadditives in 3-D nanocomposite scaffolds for bone regeneration. Journal of Materials Chemistry, 20, 8912–8919. 68. Ponnurangam, S., O’Connell, G. D., Chernyshova, I. V., Wood, K., Hung, C. T.-H., & Somasundaran, P. (2014). Beneﬁcial effects of cerium oxide nanoparticles in development of chondrocyte-seeded hydrogel constructs and cellular response to interleukin insults. Tissue Engineering Part A, 20, 2908–2919. 69. Pulido-Reyes, G., Rodea-Palomares, I., Das, S., Sakthivel, T. S., Leganes, F., Rosal, R., et al. (2015). Untangling the biological effects of cerium oxide nanoparticles: the role of surface valence states. Scientiﬁc Reports, 5, 15613. 70. Hirst, S. M., Karakoti, A. S., Tyler, R. D., Sriranganathan, N., Seal, S., & Reilly, C. M. (2009). Anti-inflammatory properties of cerium oxide nanoparticles. Small (Weinheim an der Bergstrasse, Germany), 5, 2848–2856. 71. Oro, D., Yudina, T., Fernandez-Varo, G., Casals, E., Reichenbach, V., Casals, G., et al. (2016). Cerium oxide nanoparticles reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with liver ﬁbrosis. Journal of Hepatology, 64, 691–698. 72. Perez, J. M., Asati, A., Nath, S., & Kaittanis, C. (2008). Synthesis of biocompatible dextran-coated nanoceria with pH-dependent antioxidant properties. Small (Weinheim an der Bergstrasse, Germany), 4, 552–556. 73. Lee, S. S., Song, W., Cho, M., Puppala, H. L., Phuc, N., Zhu, H., et al. (2013). Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal diameter and surface coating. ACS Nano, 7, 9693–9703. 74. Pelletier, D. A., Suresh, A. K., Holton, G. A., McKeown, C. K., Wang, W., Gu, B., et al. (2010). Effects of engineered cerium oxide nanoparticles on bacterial growth and viability. Applied and Environmental Microbiology, 76, 7981–7989. 75. Shah, V., Shah, S., Shah, H., Rispoli, F. J., McDonnell, K. T., Workeneh, S., et al. (2012). Antibacterial activity of polymer coated cerium oxide nanoparticles. PLoS ONE, 7, e0047827. 76. Son, D., Lee, J., Lee, D. J., Ghaffari, R., Yun, S., Kim, S. J., et al. (2015). Bioresorbable electronic stent integrated with therapeutic nanoparticles for endovascular diseases. ACS Nano, 9, 5937–5946. 77. Liu, B. W., Sun, Z. Y., Huang, P. J. J., & Liu, J. W. (2015). Hydrogen peroxide displacing DNA from nanoceria: Mechanism and detection of glucose in serum. Journal of the American Chemical Society, 137, 1290–1295. 78. Pirmohamed, T., Dowding, J. M., Singh, S., Wasserman, B., Heckert, E., Karakoti, A. S., et al. (2010). Nanoceria exhibit redox state-dependent catalase mimetic activity. Chemical Communications, 46, 2736–2738.

References

87

79. Nicolini, V., Gambuzzi, E., Malavasi, G., Menabue, L., Menziani, M. C., Lusvardi, G., et al. (2015). Evidence of catalase mimetic activity in Ce3+/Ce4+ doped bioactive glasses. Journal of Physical Chemistry B, 119, 4009–4019. 80. Gao, W., Wei, X., Wang, X., Cui, G., Liu, Z., & Tang, B. (2016). A competitive coordination-based CeO2 nanowire-DNA nanosensor: fast and selective detection of hydrogen peroxide in living cells and in vivo. Chemical Communications, 52, 3643–3646. 81. Tian, Z. M., Li, J., Zhang, Z. Y., Gao, W., Zhou, X. M., & Qu, Y. Q. (2015). Highly sensitive and robust peroxidase-like activity of porous nanorods of ceria and their application for breast cancer detection. Biomaterials, 59, 116–124. 82. Artiglia, L., Agnoli, S., Paganini, M. C., Cattelan, M., & Granozzi, G. (2014). TiO2@CeOx core-shell nanoparticles as artiﬁcial enzymes with peroxidase-like activity. ACS Applied Materials & Interfaces, 6, 20130–20136. 83. Asati, A., Santra, S., Kaittanis, C., Nath, S., & Perez, J. M. (2009). Oxidase-like activity of polymer-coated cerium oxide nanoparticles. Angewandte Chemie-International Edition, 48, 2308–2312. 84. Pautler, R., Kelly, E. Y., Huang, P. J. J., Cao, J., Liu, B. W., & Liu, J. W. (2013). Attaching DNA to nanoceria: Regulating oxidase activity and fluorescence quenching. ACS Applied Materials & Interfaces, 5, 6820–6825. 85. Kim, M. I., Park, K. S., & Park, H. G. (2014). Ultrafast colorimetric detection of nucleic acids based on the inhibition of the oxidase activity of cerium oxide nanoparticles. Chemical Communications, 50, 9577–9580. 86. Dowding, J. M., Dosani, T., Kumar, A., Seal, S., & Self, W. T. (2012). Cerium oxide nanoparticles scavenge nitric oxide radical (∙NO). Chemical Communications, 48, 4896–4898. 87. Vernekar, A. A., Das, T., & Mugesh, G. (2016). Vacancy-engineered nanoceria: Enzyme mimetic hotspots for the degradation of nerve agents. Angewandte Chemie-International Edition, 55, 1412–1416. 88. Gao, L. Z., Zhuang, J., Nie, L., Zhang, J. B., Zhang, Y., Gu, N., et al. (2007). Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nature Nanotechnology, 2, 577–583. 89. Wang, L. J., Min, Y., Xu, D. D., Yu, F. J., Zhou, W. Z., & Cuschieri, A. (2014). Membrane lipid peroxidation by the peroxidase-like activity of magnetite nanoparticles. Chemical Communications, 50, 11147–11150. 90. Kim, M. I., Shim, J., Li, T., Lee, J., & Park, H. G. (2011). Fabrication of nanoporous nanocomposites entrapping Fe3O4 magnetic nanoparticles and oxidases for colorimetric biosensing. Chemistry-A European Journal, 17, 10700–10707. 91. Liu, C. H., & Tseng, W. L. (2011). Oxidase-functionalized Fe3O4 nanoparticles for fluorescence sensing of speciﬁc substrate. Analytica Chimica Acta, 703, 87–93. 92. Kim, M. I., Ye, Y., Won, B. Y., Shin, S., Lee, J., & Park, H. G. (2011). A highly efﬁcient electrochemical biosensing platform by employing conductive nanocomposite entrapping magnetic nanoparticles and oxidase in mesoporous carbon foam. Advanced Functional Materials, 21, 2868–2875. 93. Liu, S. H., Lu, F., Xing, R. M., & Zhu, J. J. (2011). Structural effects of Fe3O4 nanocrystals on peroxidase-like activity. Chemistry-A European Journal, 17, 620–625. 94. Wu, Y. H., Song, M. J., Xin, Z. A., Zhang, X. Q., Zhang, Y., Wang, C. Y., et al. (2011). Ultra-small particles of iron oxide as peroxidase for immunohistochemical detection. Nanotechnology, 22, 225703. 95. Dong, Y. L., Zhang, H. G., Rahman, Z. U., Su, L., Chen, X. J., Hu, J., et al. (2012). Graphene oxide-Fe3O4 magnetic nanocomposites with peroxidase-like activity for colorimetric detection of glucose. Nanoscale, 4, 3969–3976. 96. Kim, M. I., Shim, J., Li, T., Woo, M. A., Cho, D., Lee, J., et al. (2012). Colorimetric quantiﬁcation of galactose using a nanostructured multi-catalyst system entrapping galactose oxidase and magnetic nanoparticles as peroxidase mimetics. Analyst, 137, 1137–1143.

88

4 Metal Oxide-Based Nanomaterials for Nanozymes

97. Lee, J. W., Jeon, H. J., Shin, H. J., & Kang, J. K. (2012). Superparamagnetic Fe3O4 nanoparticles-carbon nitride nanotube hybrids for highly efﬁcient peroxidase mimetic catalysts. Chemical Communications, 48, 422–424. 98. Ma, Y. H., Zhang, Z. Y., Ren, C. L., Liu, G. Y., & Chen, X. G. (2012). A novel colorimetric determination of reduced glutathione in A549 cells based on Fe3O4 magnetic nanoparticles as peroxidase mimetics. Analyst, 137, 485–489. 99. Fan, K. L., Cao, C. Q., Pan, Y. X., Lu, D., Yang, D. L., Feng, J., et al. (2012). Magnetoferritin nanoparticles for targeting and visualizing tumour tissues. Nature Nanotechnology, 7, 459–464. 100. Zhang, X. Q., Gong, S. W., Zhang, Y., Yang, T., Wang, C. Y., & Gu, N. (2010). Prussian blue modiﬁed iron oxide magnetic nanoparticles and their high peroxidase-like activity. Journal of Materials Chemistry, 20, 5110–5116. 101. Chaudhari, K. N., Chaudhari, N. K., & Yu, J.-S. (2012). Peroxidase mimic activity of hematite iron oxides (α-Fe2O3) with different nanostructres. Catalysis Science & Technology, 2, 119–124. 102. Guo, F. F., Yang, W., Jiang, W., Geng, S., Peng, T., & Li, J. L. (2012). Magnetosomes eliminate intracellular reactive oxygen species in Magnetospirillum gryphiswaldense MSR-1. Environmental Microbiology, 14, 1722–1729. 103. Fan, Y. W., & Huang, Y. M. (2012). The effective peroxidase-like activity of chitosan-functionalized CoFe2O4 nanoparticles for chemiluminescence sensing of hydrogen peroxide and glucose. Analyst, 137, 1225–1231. 104. Shi, W. B., Wang, H., & Huang, Y. M. (2011). Luminol-silver nitrate chemiluminescence enhancement induced by cobalt ferrite nanoparticles. Luminescence, 26, 547–552. 105. Zhang, X. D., He, S. H., Chen, Z. H., & Huang, Y. M. (2013). CoFe2O4 nanoparticles as oxidase mimic-mediated chemiluminescence of aqueous luminol for sulﬁte in white wines. Journal of Agricultural and Food Chemistry, 61, 840–847. 106. Luo, W., Li, Y. S., Yuan, J., Zhu, L. H., Liu, Z. D., Tang, H. Q., et al. (2010). Ultrasensitive fluorometric determination of hydrogen peroxide and glucose by using multiferroic BiFeO3 nanoparticles as a catalyst. Talanta, 81, 901–907. 107. Bhattacharya, D., Baksi, A., Banerjee, I., Ananthakrishnan, R., Maiti, T. K., & Pramanik, P. (2011). Development of phosphonate modiﬁed Fe(1−x)MnxFe2O4 mixed ferrite nanoparticles: Novel peroxidase mimetics in enzyme linked immunosorbent assay. Talanta, 86, 337–348. 108. Yan, L., Liu, X., Liu, W.-X., Tan, X.-Q., Xiong, F., Gu, N., et al. (2015). Fe2O3 nanoparticles suppress Kv1.3 channels via affecting the redox activity of Kv2 subunit in Jurkat T cells. Nanotechnology, 26, 505103. 109. Lu, C., Liu, X., Li, Y., Yu, F., Tang, L., Hu, Y., et al. (2015). Multifunctional janus hematite silica nanoparticles: Mimicking peroxidase-like activity and sensitive colorimetric detection of glucose. ACS Applied Materials & Interfaces, 7, 15395–15402. 110. Kim, J. A., Lee, N. H., Kim, B. H., Rhee, W. J., Yoon, S., Hyeon, T., et al. (2011). Enhancement of neurite outgrowth in PC12 cells by iron oxide nanoparticles. Biomaterials, 32, 2871–2877. 111. He, X. L., Tan, L. F., Chen, D., Wu, X. L., Ren, X. L., Zhang, Y. Q., et al. (2013). Fe3O4– Au@mesoporous SiO2 microspheres: An ideal artiﬁcial enzymatic cascade system. Chemical Communications, 49, 4643–4645. 112. An, Q., Sun, C. Y., Li, D., Xu, K., Guo, J., & Wang, C. C. (2013). Peroxidase-like activity of Fe3O4@carbon nanoparticles enhances ascorbic acid-induced oxidative stress and selective damage to PC-3 prostate cancer cells. ACS Applied Materials & Interfaces, 5, 13248–13257. 113. Gao, L. Z., Giglio, K. M., Nelson, J. L., Sondermann, H., & Travis, A. J. (2014). Ferromagnetic nanoparticles with peroxidase-like activity enhance the cleavage of biological macromolecules for bioﬁlm elimination. Nanoscale, 6, 2588–2593. 114. Su, L., Feng, J., Zhou, X. M., Ren, C. L., Li, H. H., & Chen, X. G. (2012). Colorimetric detection of urine glucose based ZnFe2O4 magnetic nanoparticles. Analytical Chemistry, 84, 5753–5758.

References

89

115. Li, Q., Tang, G. G., Xiong, X. W., Cao, Y. L., Chen, L. L., Xu, F. G., et al. (2015). Carbon coated magnetite nanoparticles with improved water-dispersion and peroxidase-like activity for colorimetric sensing of glucose. Sensors and Actuators B-Chemical, 215, 86–92. 116. Shin, S., Yoon, H., & Jang, J. (2008). Polymer-encapsulated iron oxide nanoparticles as highly efﬁcient Fenton catalysts. Catalysis Communications, 10, 178–182. 117. Wang, N., Zhu, L. H., Wang, D. L., Wang, M. Q., Lin, Z. F., & Tang, H. Q. (2010). Sono-assisted preparation of highly-efﬁcient peroxidase-like Fe3O4 magnetic nanoparticles for catalytic removal of organic pollutants with H2O2. Ultrasonics Sonochemistry, 17, 526–533. 118. Niu, H. Y., Zhang, D., Zhang, S. X., Zhang, X. L., Meng, Z. F., & Cai, Y. Q. (2011). Humic acid coated Fe3O4 magnetic nanoparticles as highly efﬁcient Fenton-like catalyst for complete mineralization of sulfathiazole. Journal of Hazardous Materials, 190, 559–565. 119. Wei, H., & Wang, E. (2008). Fe3O4 magnetic nanoparticles as peroxidase mimetics and their applications in H2O2 and glucose detection. Analytical Chemistry, 80, 2250–2254. 120. Wang, X. Y., Hu, Y. H., & Wei, H. (2016). Nanozymes in bionanotechnology: From sensing to therapeutics and beyond. Inorganic Chemistry Frontiers, 3, 41–60. 121. Liang, M. M., Fan, K. L., Pan, Y., Jiang, H., Wang, F., Yang, D. L., et al. (2013). Fe3O4 magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent. Analytical Chemistry, 85, 308–312. 122. Park, K. S., Kim, M. I., Cho, D. Y., & Park, H. G. (2011). Label-free colorimetric detection of nucleic acids based on target-induced shielding against the peroxidase-mimicking activity of magnetic nanoparticles. Small (Weinheim an der Bergstrasse, Germany), 7, 1521–1525. 123. Thiramanas, R., Jangpatarapongsa, K., Tangboriboonrat, P., & Polpanich, D. (2013). Detection of vibrio cholerae using the intrinsic catalytic activity of a magnetic polymeric nanoparticle. Analytical Chemistry, 85, 5996–6002. 124. Liu, B. W., & Liu, J. W. (2015). Accelerating peroxidase mimicking nanozymes using DNA. Nanoscale, 7, 13831–13835. 125. Duan, D., Fan, K., Zhang, D., Tan, S., Liang, M., Liu, Y., et al. (2015). Nanozyme-strip for rapid local diagnosis of Ebola. Biosensors & Bioelectronics, 74, 134–141. 126. Gao, L. Z., Wu, J. M., Lyle, S., Zehr, K., Cao, L. L., & Gao, D. (2008). Magnetite nanoparticle-linked immunosorbent assay. Journal of Physical Chemistry C, 112, 17357–17361. 127. Kaittanis, C., Santra, S., & Perez, J. M. (2009). Role of nanoparticle valency in the nondestructive magnetic-relaxation-mediated detection and magnetic isolation of cells in complex media. Journal of the American Chemical Society, 131, 12780–12791. 128. Zhang, Z. X., Wang, Z. J., Wang, X. L., & Yang, X. R. (2010). Magnetic nanoparticle-linked colorimetric aptasensor for the detection of thrombin. Sensors and Actuators B-Chemical, 147, 428–433. 129. Zheng, T. T., Zhang, Q. F., Feng, S., Zhu, J. J., Wang, Q., & Wang, H. (2014). Robust nonenzymatic hybrid nanoelectrocatalysts for signal ampliﬁcation toward ultrasensitive electrochemical cytosensing. Journal of the American Chemical Society, 136, 2288–2291. 130. Zhang, S., Zhou, G. L., Xu, X. L., Cao, L. L., Liang, G. H., Chen, H., et al. (2011). Development of an electrochemical aptamer-based sensor with a sensitive Fe3O4 nanoparticle-redox tag for reagentless protein detection. Electrochemistry Communications, 13, 928–931. 131. Chen, Z. W., Yin, J. J., Zhou, Y. T., Zhang, Y., Song, L., Song, M. J., et al. (2012). Dual enzyme-like activities of iron oxide nanoparticles and their implication for diminishing cytotoxicity. ACS Nano, 6, 4001–4012. 132. Zhang, Y., Wang, Z. Y., Li, X. J., Wang, L., Yin, M., Wang, L. H., et al. (2016). Dietary iron oxide nanoparticles delay aging and ameliorate neurodegeneration in drosophila. Advanced Materials, 28, 1387–1393. 133. Xiong, F., Wang, H., Feng, Y. D., Li, Y. M., Hua, X. Q., Pang, X. Y., et al. (2015). Cardioprotective activity of iron oxide nanoparticles. Scientiﬁc Reports, 5, 8579.

90

4 Metal Oxide-Based Nanomaterials for Nanozymes

134. Li, Q., Tang, G., Xue, S., He, X., Miao, P., Li, Y., et al. (2013). Silica-coated superparamagnetic iron oxide nanoparticles targeting of EPCs in ischemic brain injury. Biomaterials, 34, 4982–4992. 135. Wang, Q., Chen, B., Cao, M., Sun, J., Wu, H., Zhao, P., et al. (2016). Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. Biomaterials, 86, 11–20. 136. Andre, R., Natalio, F., Humanes, M., Leppin, J., Heinze, K., Wever, R., et al. (2011). V2O5 Nanowires with an intrinsic peroxidase-like activity. Advanced Functional Materials, 21, 501–509. 137. Natalio, F., Andre, R., Hartog, A. F., Stoll, B., Jochum, K. P., Wever, R., et al. (2012). Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart bioﬁlm formation. Nature Nanotechnology, 7, 530–535. 138. Vernekar, A. A., Sinha, D., Srivastava, S., Paramasivam, P. U., D’Silva, P., & Mugesh, G. (2014). An antioxidant nanozyme that uncovers the cytoprotective potential of vanadia nanowires. Nature Communications, 5, 5301. 139. Han, L., Zeng, L. X., Wei, M. D., Li, C. M., & Liu, A. H. (2015). A V2O3-ordered mesoporous carbon composite with novel peroxidase-like activity towards the glucose colorimetric assay. Nanoscale, 7, 11678–11685. 140. Deng, H. M., Shen, W., Peng, Y. F., Chen, X. J., Yi, G. S., & Gao, Z. Q. (2012). Nanoparticulate peroxidase/catalase mimetic and its application. Chemistry-A European Journal, 18, 8906–8911. 141. Wu, M., Meng, S., Wang, Q., Si, W., Huang, W., & Dong, X. (2015). Nickel-cobalt oxide decorated three-dimensional graphene as an enzyme mimic for glucose and calcium detection. ACS Applied Materials & Interfaces, 7, 21089–21094. 142. Qu, K. G., Shi, P., Ren, J. S., & Qu, X. G. (2014). Nanocomposite incorporating V2O5 nanowires and gold nanoparticles for mimicking an enzyme cascade reaction and its application in the detection of biomolecules. Chemistry-A European Journal, 20, 7501–7506. 143. Cha, S.-H., Hong, J., McGufﬁe, M., Yeom, B., VanEpps, J. S., & Kotov, N. A. (2015). Shape-dependent biomimetic inhibition of enzyme by nanoparticles and their antibacterial activity. ACS Nano, 9, 9097–9105. 144. Wan, Y., Qi, P., Zhang, D., Wu, J. J., & Wang, Y. (2012). Manganese oxide nanowire-mediated enzyme-linked immunosorbent assay. Biosensors & Bioelectronics, 33, 69–74. 145. Zhang, X. D., & Huang, Y. M. (2015). Evaluation of the antioxidant activity of phenols and tannic acid determination with Mn3O4 nano-octahedrons as an oxidase mimic. Analytical Methods, 7, 8640–8646. 146. Jin, L. Y., Dong, Y. M., Wu, X. M., Cao, G. X., & Wang, G. L. (2015). Versatile and ampliﬁed biosensing through enzymatic cascade reaction by coupling alkaline phosphatase in situ generation of photoresponsive nanozyme. Analytical Chemistry, 87, 10429–10436. 147. Chen, W., Chen, J., Feng, Y. B., Hong, L., Chen, Q. Y., Wu, L. F., et al. (2012). Peroxidase-like activity of water-soluble cupric oxide nanoparticles and its analytical application for detection of hydrogen peroxide and glucose. Analyst, 137, 1706–1712. 148. Zhang, L. L., Han, L., Hu, P., Wang, L., & Dong, S. J. (2013). TiO2 nanotube arrays: Intrinsic peroxidase mimetics. Chemical Communications, 49, 10480–10482. 149. Ragg, R., Natalio, F., Tahir, M. N., Janssen, H., Kashyap, A., Strand, D., et al. (2014). Molybdenum trioxide nanoparticles with intrinsic sulﬁte oxidase activity. ACS Nano, 8, 5182–5189. 150. Dong, J. L., Song, L. N., Yin, J. J., He, W. W., Wu, Y. H., Gu, N., et al. (2014). Co3O4 nanoparticles with multi-enzyme activities and their application in immunohistochemical assay. ACS Applied Materials & Interfaces, 6, 1959–1970. 151. Qu, K., Shi, P., Ren, J., & Qu, X. (2014). Nanocomposite incorporating V2O5 nanowires and gold nanoparticles for mimicking an enzyme cascade reaction and its application in the detection of biomolecules. Chemistry-A European Journal, 20, 7501–7506.

References

91

152. Mu, J. S., Zhang, L., Zhao, M., & Wang, Y. (2013). Co3O4 nanoparticles as an efﬁcient catalase mimic: Properties, mechanism and its electrocatalytic sensing application for hydrogen peroxide. Journal of Molecular Catalysis A-Chemical, 378, 30–37. 153. Zhang, H., Pokhrel, S., Ji, Z., Meng, H., Wang, X., Lin, S., et al. (2014). PdO doping tunes band-gap energy levels as well as oxidative stress responses to a Co3O4 p-type semiconductor in cells and the lung. Journal of the American Chemical Society, 136, 6406–6420. 154. Mu, J. S., Zhang, L., Zhao, M., & Wang, Y. (2014). Catalase mimic property of Co3O4 nanomaterials with different morphology and its application as a calcium sensor. ACS Applied Materials & Interfaces, 6, 7090–7098. 155. Chen, W., Chen, J., Liu, A. L., Wang, L. M., Li, G. W., & Lin, X. H. (2011). Peroxidase-like activity of cupric oxide nanoparticle. ChemCatChem, 3, 1151–1154. 156. Hu, A. L., Liu, Y. H., Deng, H. H., Hong, G. L., Liu, A. L., Lin, X. H., et al. (2014). Fluorescent hydrogen peroxide sensor based on cupric oxide nanoparticles and its application for glucose and L-lactate detection. Biosensors & Bioelectronics, 61, 374–378. 157. Li, G.-W., Hong, L., Tong, M.-S., Deng, H.-H., Xia, X.-H., & Chen, W. (2015). Determination of tannic acid based on luminol chemiluminescence catalyzed by cupric oxide nanoparticles. Analytical Methods, 7, 1924–1928. 158. Wu, C. W., Harroun, S. G., Lien, C. W., Chang, H. T., Unnikrishnan, B., Lai, I. P. J., et al. (2016). Self-templated formation of aptamer-functionalized copper oxide nanorods with intrinsic peroxidase catalytic activity for protein and tumor cell detection. Sensors and Actuators B-Chemical, 227, 100–107. 159. Applerot, G., Lellouche, J., Lipovsky, A., Nitzan, Y., Lubart, R., Gedanken, A., et al. (2012). Understanding the antibacterial mechanism of cuo nanoparticles: Revealing the route of induced oxidative stress. Small (Weinheim an der Bergstrasse, Germany), 8, 3326–3337. 160. Ragavan, K. V., & Rastogi, N. K. (2016). Graphene-copper oxide nanocomposite with intrinsic peroxidase activity for enhancement of chemiluminescence signals and its application for detection of bisphenol-A. Sensors and Actuators B-Chemical, 229, 570–580. 161. Li, G. L., Ma, P., Zhang, Y. F., Liu, X. L., Zhang, H., Xue, W. M., et al. (2016). Synthesis of Cu2O nanowire mesocrystals using PTCDA as a modiﬁer and their superior peroxidase-like activity. Journal of Materials Science, 51, 3979–3988. 162. Liu, Y. J., Zhu, G. X., Bao, C. L., Yuan, A. H., & Shen, X. P. (2014). Intrinsic peroxidase-like activity of porous CuO micro-/nanostructures with clean surface. Chinese Journal of Chemistry, 32, 151–156. 163. Chen, W., Hong, L., Liu, A.-L., Liu, J.-Q., Lin, X.-H., & Xia, X.-H. (2012). Enhanced chemiluminescence of the luminol-hydrogen peroxide system by colloidal cupric oxide nanoparticles as peroxidase mimic. Talanta, 99, 643–648. 164. Hong, L., Liu, A.-L., Li, G.-W., Chen, W., & Lin, X.-H. (2013). Chemiluminescent cholesterol sensor based on peroxidase-like activity of cupric oxide nanoparticles. Biosensors & Bioelectronics, 43, 1–5.

Chapter 5

Other Nanomaterials for Nanozymes

Abstract The use of other nanomaterials beyond carbon-based nanomaterials, metal-based nanomaterials, and metal oxide-based nanomaterials for mimicking natural enzymes is discussed in this chapter. Prussian blue, metal-organic frameworks, metal chalcogenides, metal hydroxides, etc., have been selected as representative nanomaterials for mimicking peroxidase, superoxide dismutase, catalase, etc. The catalytic mechanisms are also discussed if they have been elucidated. Selected examples for in vitro biosensing, in vivo bioanalysis, and therapeutics are discussed to highlight the broad applications of these nanozymes.

Keywords Nanozymes Artiﬁcial enzymes Integrated nanozymes Prussian blue Metal-organic frameworks Metal chalcogenides Metal hydroxides Cascade reactions Enzyme mimics Functional nanomaterials

As discussed in Chap. 1, more and more nanomaterials have been explored to investigate their enzyme mimicking activities [1–60]. To highlight the evergrowing interests in searching for new nanozymes, in this chapter selected examples of other nanomaterials for nanozymes are discussed.

5.1

Prussian Blue

Prussian blue, [Fe(III)Fe(II)(CN)6]−, based nanomaterials have been used to mimic peroxidase, catalase, and SOD [4–6, 61]. In their initial report, Gu et al. found that the Prussian blue coating could enhance the peroxidase mimicking activity of γ-Fe2O3 nanoparticles [3]. Later, they showed that Prussian blue nanoparticles exhibited catalase-like activity at neutral conditions (i.e., pH = 7.4) [4]. The nanozyme was used for in vivo ultrasound and magnetic-resonance imaging of overproduced H2O2 in diseased tissues. The nanozyme converted H2O2 into O2 gas bubbles, which acted as the ultrasound contrast agents. Moreover, due to the paramagnetic property of the formed O2 gas bubbles, they also acted as T1 © The Author(s) 2016 X. Wang et al., Nanozymes: Next Wave of Artiﬁcial Enzymes, SpringerBriefs in Molecular Science, DOI 10.1007/978-3-662-53068-9_5

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Fig. 5.1 a Schematic showing intracellular behaviors of Prussian blue nanoparticles (PBNPs). b Proposed mechanisms of the multiple enzyme-like activities of PBNPs based on standard redox potentials of different compounds in the reaction systems. c Reactions involved. Prussian white (PW, [Fe(II)Fe(II)(CN)6]2−), Berlin green (BG, {Fe(III)3[Fe(III)(CN)6]2[Fe(II)(CN)6]}2−), and Prussian yellow (PY, [Fe(II)Fe(III)(CN)6]). Reprinted from Ref. [5], Copyright 2016, with permission from American Chemical Society

5.1 Prussian Blue

95

magnetic-resonance contrast agents [4]. Using a lipopolysaccharide (LPS)-induced liver inflammation model, the overproduced H2O2 in living mouse livers was successfully imaged both by ultrasound and magnetic resonance methods. Recently, Gu et al. [5] further conﬁrmed that Prussian blue nanoparticles possessed peroxidase-like, catalase-like, and SOD-like activities (Fig. 5.1). Detailed experimental results suggested that the peroxidase mimicking activity was dominant at acidic conditions while the catalase mimicking activity was dominant at high pH conditions. Interestingly, Prussian blue nanoparticles exhibited SOD-like activities at different pH levels. Due to the mixed valence of Fe2+ and Fe3+, Prussian blue can be reduced into Prussian white and oxidized into Berlin green or Prussian yellow. As shown in Fig. 5.1b, the peroxidase-like activity was attributed to the following mechanism: Prussian blue was ﬁrst oxidized into Prussian yellow or Berlin green by H2O2 at acidic pH (Eq. 5.6). Prussian yellow/Berlin green would then oxidize TMB to into TMBox. Therefore, Prussian yellow/Berlin as the peroxidase mimic transferred electrons from TMB to H2O2 to achieve the catalytic recycle (Eq. 5.7). Since H2O2 could act both as oxidizing and reducing agents, the presence of the nanozyme would dismutate H2O2 into H2O and O2 via the mechanisms shown in Eqs. 5.8–5.11. Similarly, superoxide anion could be converted into H2O2 and O2 via the mechanisms shown in Eqs. 5.12–5.16. They further demonstrated that the nanozymes could alleviate inflammation by scavenging ROS in vivo in lipopolysaccharide-treated mice model [5].

5.2

Metal-Organic Frameworks

Metal-organic frameworks (MOFs) themselves and MOFs loaded with other catalysts have been used to mimic natural enzymes [7–18]. For instance, it has reported that a well-known Cu2+ and benzene-1,3,5-tricarboxylate ligand-based MOF (i.e., HKUST-1) could mimic protease. Similar with natural trypsin, HKUST-1 could catalyze the hydrolysis of bovine serum albumin (BSA) and casein. Moreover, in comparison with natural trypsin, the MOF-based nanozyme had higher afﬁnity toward BSA [9]. For MOFs made from non-redox active metal ions, they could be imparted with catalytic activities by encapsulating guest catalysts [7, 8, 15]. Usually, one catalyst was usually encapsulated within MOFs for catalysis [15]. In biological systems, however, multiple enzymes are usually compartmentalized within subcellular organelles for cascade catalytic reactions. Such compartmentalization would lead to an interesting “nanoscale proximity effects,” which could signiﬁcantly enhance the coupled reactions via several mechanisms. For example, it could improve the local concentrations of catalysts and substrates, reduce the diffusion barrier, and stabilize the catalysts and the unstable intermediates. Inspired by this, several strategies have been developed to co-encapsulate two catalysts guests within various matrix [7, 8, 62–66].

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Wei and co-workers [7, 8] have developed a self-assembly strategy to fabricate integrated nanozymes (INAzymes) by co-assembling multiple catalytic guests within MOFs (Fig. 5.2). They ﬁrst demonstrated that molecular catalysts (e.g., hemin) and natural enzymes (e.g., GOx) could be simultaneously conﬁned with ZIF-8, a MOF made from Zn2+ and 2-methylimidazole ligands, under biocompatible reaction conditions (Fig. 5.2a). Moreover, the obtained INAzyme of hemin and GOx exhibited more than 600 % enhancement of the catalytic activity when compared with the mixture of hemin@ZIF-8 and GOx@ZIF-8 (Fig. 5.2c). After establishing that the INAzyme could be used for sensitive and selective detection of glucose in vitro, they went on to construct an analytical platform by immobilizing the INAzyme into the channel of a microfluidics chip. When further assisted with microdialysis, the dynamic changes of brain glucose following ischemia and perfusion has been successfully monitored with the platform (Fig. 5.2d, e). Their strategy was general and applicable to other combination of catalyst guests (such as hemin/lactate oxidase and hemin/GOx/invertase) [8].

Fig. 5.2 Integrated nanozymes for monitoring the dynamic changes of brain glucose following ischemia/reperfusion. a Schematic and TEM image of the integrated nanozymes (INAzymes). b Reactions catalyzed by the INAzymes. c Normalized cascade catalytic activity of the INAzyme (1), and the mixture of hemin@ZIF-8 and GOx@ZIF-8 (2), showing a more than 600 % enhancement for the INAzyme when compared with the mixture of hemin@ZIF-8 and GOx@ZIF-8. d Schematic illustration of the global cerebral ischemia. e Continuously monitoring the dynamic changes of glucose level in the striatum of a living rat brain following global ischemia/reperfusion with the INAzyme-based sensing platform. Adapted from Ref. [8], Copyright 2016, with permission from American Chemical Society

5.3 Metal Chalcogenides

5.3

97

Metal Chalcogenides

Numerous studies have showed that metal chalcogenides (such as CuS, MnSe, and FeSe) could mimic peroxidase [19–34]. For example, Huang et al. prepared NiTe nanowires via a hydrothermal method. The obtained NiTe nanowires showed peroxidase mimicking activity, which were better than the commercial NiTe powders. They further combined the nanozyme with GOx for sensitive and selective detection of glucose [24].

5.4

Metal Hydroxides

Metal hydroxides, including layered double hydroxides, have been explored to mimic peroxidase [35–38]. For example, Sun et al. reported the peroxidase-like activity of CoFe layered double hydroxides and used them for colorimetric detection of H2O2 and glucose [37]. Tan’s group fabricated an interesting Cu(OH)2 nanocages from amorphous Cu(OH)2 nanoparticles. Catalytic studies revealed that the nanocages showed higher peroxidase mimicking activities even than that of natural enzymes (Fig. 5.3) [38].

Fig. 5.3 Cu(OH)2 nanocages as peroxidase mimics. Reprinted from Ref. [38], Copyright 2015, with permission from American Chemical Society

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Fig. 5.4 a SEM image of polypyrrole/hemin nanocomposites. b Polypyrrole/hemin nanocomposites as peroxidase mimics for glucose sensing. Adapted from Ref. [54], Copyright 2014, with permission from American Chemical Society

5.5

Miscellaneous

Lots of other materials have been reported to mainly mimic peroxidase [39–60, 67]. For example, magnetic zirconium hexacyanoferrate (II) nanoparticles as peroxidase mimics were used to label probe ssDNA for electrochemical DNA sensing [56]. Dong et al. [54] developed a facile way to prepare polypyrrole/hemin nanocomposites by chemical oxidative polymerization of pyrrole monomer with FeCl3 in the presence of hemin (Fig. 5.4). The peroxidase-like activity of the nanocomposites was conﬁrmed by catalyzing the oxidation of TMB and other peroxidase substrates with H2O2. When the peroxidase mimics were combined with GOx, the selective and sensitive detection of glucose was achieved [54].

References 1. Wei, H., & Wang, E. K. (2013). Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artiﬁcial enzymes. Chemical Society Reviews, 42, 6060–6093. 2. Wang, X. Y., Hu, Y. H., & Wei, H. (2016). Nanozymes in bionanotechnology: From sensing to therapeutics and beyond. Inorganic Chemistry Frontiers, 3, 41–60. 3. Zhang, X.-Q., Gong, S.-W., Zhang, Y., Yang, T., Wang, C.-Y., & Gu, N. (2010). Prussian blue modiﬁed iron oxide magnetic nanoparticles and their high peroxidase-like activity. Journal of Materials Chemistry, 20, 5110–5116. 4. Yang, F., Hu, S., Zhang, Y., Cai, X., Huang, Y., Wang, F., et al. (2012). A hydrogen peroxide-responsive O2 nanogenerator for ultrasound and magnetic-resonance dual modality imaging. Advanced Materials, 24, 5205–5211. 5. Zhang, W., Hu, S. L., Yin, J. J., He, W. W., Lu, W., Ma, M., et al. (2016). Prussian blue nanoparticles as multienzyme mimetics and reactive oxygen species scavengers. Journal of the American Chemical Society, 138, 5860–5865.

References

99

6. Liu, T., Niu, X., Shi, L., Zhu, X., Zhao, H., & Lana, M. (2015). Electrocatalytic analysis of superoxide anion radical using nitrogen-doped graphene supported Prussian Blue as a biomimetic superoxide dismutase. Electrochimica Acta, 176, 1280–1287. 7. Cheng, H. J., Wei, H. (2014). Gordon Research Conference: Bioanalytical Sensors, Newport, RI, USA, June 22–27, 2014. 8. Cheng, H. J., Zhang, L., He, J., Guo, W. J., Zhou, Z. Y., Zhang, X. J., et al. (2016). Integrated nanozymes with nanoscale proximity for in vivo neurochemical monitoring in living brains. Analytical Chemistry, 88, 5489–5497. 9. Li, B., Chen, D. M., Wang, J. Q., Yan, Z. Y., Jiang, L., Duan, D. L., et al. (2014). MOFzyme: Intrinsic protease-like activity of Cu-MOF. Scientiﬁc Reports, 4, 6759. 10. Dong, W. F., Liu, X. D., Shi, W. B., & Huang, Y. M. (2015). Metal-organic framework MIL-53(Fe): Facile microwave-assisted synthesis and use as a highly active peroxidase mimetic for glucose biosensing. RSC Advances, 5, 17451–17457. 11. Ai, L. H., Li, L. L., Zhang, C. H., Fu, J., & Jiang, J. (2013). MIL-53(Fe): A metal-organic framework with intrinsic peroxidase-like catalytic activity for colorimetric biosensing. Chemistry-A European Journal, 19, 15105–15108. 12. Cui, F. J., Deng, Q. F., & Sun, L. (2015). Prussian blue modiﬁed metal-organic framework MIL-101(Fe) with intrinsic peroxidase-like catalytic activity as a colorimetric biosensing platform. RSC Advances, 5, 98215–98221. 13. Deleu, W. P. R., Rivero, G., Teixeira, R. F. A., Du Prez, F. E., & De Vos, D. E. (2015). Metal organic frameworks encapsulated in photocleavable capsules for uv-light triggered catalysis. Chemistry of Materials, 27, 5495–5502. 14. Xiong, Y. H., Chen, S. H., Ye, F. G., Su, L. J., Zhang, C., Shen, S. F., et al. (2015). Synthesis of a mixed valence state Ce-MOF as an oxidase mimetic for the colorimetric detection of biothiols. Chemical Communications, 51, 4635–4638. 15. Qin, F.-X., Jia, S.-Y., Wang, F.-F., Wu, S.-H., Song, J., & Liu, Y. (2013). Hemin@metal-organic framework with peroxidase-like activity and its application to glucose detection. Catalysis Science & Technology, 3, 2761–2768. 16. Liu, Y. L., Zhao, X. J., Yang, X. X., & Li, Y. F. (2013). A nanosized metal-organic framework of Fe-MIL-88NH2 as a novel peroxidase mimic used for colorimetric detection of glucose. Analyst, 138, 4526–4531. 17. Lu, J., Xiong, Y., Liao, C., & Ye, F. (2015). Colorimetric detection of uric acid in human urine and serum based on peroxidase mimetic activity of MIL-53(Fe). Analytical Methods, 7, 9894–9899. 18. Chen, D. M., Li, B., Jiang, L., Duan, D. L., Li, Y. Z., Wang, J. Q., et al. (2015). Highly efﬁcient colorimetric detection of cancer cells utilizing Fe-MIL-101 with intrinsic peroxidase-like catalytic activity over a broad pH range. RSC Advances, 5, 97910–97917. 19. He, W. W., Jia, H. M., Li, X. X., Lei, Y., Li, J., Zhao, H. X., et al. (2012). Understanding the formation of CuS concave superstructures with peroxidase-like activity. Nanoscale, 4, 3501–3506. 20. Chen, Q., Chen, J., Gao, C. J., Zhang, M. L., Chen, J. Y., & Qiu, H. D. (2015). Hemin-functionalized WS2 nanosheets as highly active peroxidase mimetics for label-free colorimetric detection of H2O2 and glucose. Analyst, 140, 2857–2863. 21. Qiao, F., Wang, Z., Xu, K., & Ai, S. (2015). Double enzymatic cascade reactions within FeSe-Pt@SiO2 nanospheres: Synthesis and application toward colorimetric biosensing of H2O2 and glucose. Analyst, 140, 6684–6691. 22. Guan, J. F., Peng, J., & Jin, X. Y. (2015). Synthesis of copper sulﬁde nanorods as peroxidase mimics for the colorimetric detection of hydrogen peroxide. Analytical Methods, 7, 5454–5461. 23. Lin, T. R., Zhong, L. S., Song, Z. P., Guo, L. Q., Wu, H. Y., Guo, Q. Q., et al. (2014). Visual detection of blood glucose based on peroxidase-like activity of WS2 nanosheets. Biosensors & Bioelectronics, 62, 302–307.

100

5 Other Nanomaterials for Nanozymes

24. Wan, L. J., Liu, J. H., & Huang, X. J. (2014). Novel magnetic nickel telluride nanowires decorated with thorns: synthesis and their intrinsic peroxidase-like activity for detection of glucose. Chemical Communications, 50, 13589–13591. 25. Yao, W. T., Zhu, H. Z., Li, W. G., Yao, H. B., Wu, Y. C., & Yu, S. H. (2013). Intrinsic peroxidase catalytic activity of Fe7S8 nanowires templated from [Fe16S20]/diethylenetriamine hybrid nanowires. ChemPlusChem, 78, 723–727. 26. Wang, Y., Zhang, D., & Xiang, Z. (2015). Synthesis of α-MnSe crystal as a robust peroxidase mimic. Materials Research Bulletin, 67, 152–157. 27. Cai, Q., Lu, S. K., Liao, F., Li, Y. Q., Ma, S. Z., & Shao, M. W. (2014). Catalytic degradation of dye molecules and in situ SERS monitoring by peroxidase-like Au/CuS composite. Nanoscale, 6, 8117–8123. 28. Dalui, A., Pradhan, B., Thupakula, U., Khan, A. H., Kumar, G. S., Ghosh, T., et al. (2015). Insight into the mechanism revealing the peroxidase mimetic catalytic activity of quaternary CuZnFeS nanocrystals: Colorimetric biosensing of hydrogen peroxide and glucose. Nanoscale, 7, 9062–9074. 29. Lin, T. R., Zhong, L. S., Guo, L. Q., Fu, F. F., & Chen, G. N. (2014). Seeing diabetes: Visual detection of glucose based on the intrinsic peroxidase-like activity of MoS2 nanosheets. Nanoscale, 6, 11856–11862. 30. Lu, X. F., Bian, X. J., Li, Z. C., Chao, D. M., & Wang, C. (2013). A facile strategy to decorate Cu9S5 nanocrystals on polyaniline nanowires and their synergetic catalytic properties. Scientiﬁc Reports, 3, 2955. 31. Dutta, A. K., Maji, S. K., Mondal, A., Karmakar, B., Biswas, P., & Adhikary, B. (2012). Iron selenide thin ﬁlm: Peroxidase-like behavior, glucose detection and amperometric sensing of hydrogen peroxide. Sensors and Actuators B-Chemical, 173, 724–731. 32. Qiao, F. M., Chen, L. J., Li, X. N., Li, L. F., & Ai, S. Y. (2014). Peroxidase-like activity of manganese selenide nanoparticles and its analytical application for visual detection of hydrogen peroxide and glucose. Sensors and Actuators B-Chemical, 193, 255–262. 33. Dutta, A. K., Das, S., Samanta, S., Samanta, P. K., Adhikary, B., & Biswas, P. (2013). CuS nanoparticles as a mimic peroxidase for colorimetric estimation of human blood glucose level. Talanta, 107, 361–367. 34. Zhao, K., Gu, W., Zheng, S., Zhang, C., & Xian, Y. (2015). SDS-MoS2 nanoparticles as highly-efﬁcient peroxidase mimetics for colorimetric detection of H2O2 and glucose. Talanta, 141, 47–52. 35. Wang, Y. L., Chen, S. H., Ni, F., Gao, F., & Li, M. G. (2009). Peroxidase-like layered double hydroxide nanoflakes for electrocatalytic reduction of H2O2. Electroanalysis, 21, 2125–2132. 36. Cui, L., Yin, H. S., Dong, J., Fan, H., Liu, T., Ju, P., et al. (2011). A mimic peroxidase biosensor based on calcined layered double hydroxide for detection of H2O2. Biosensors & Bioelectronics, 26, 3278–3283. 37. Zhang, Y. W., Tian, J. Q., Liu, S., Wang, L., Qin, X. Y., Lu, W. B., et al. (2012). Novel application of CoFe layered double hydroxide nanoplates for colorimetric detection of H2O2 and glucose. Analyst, 137, 1325–1328. 38. Cai, R., Yang, D., Peng, S. J., Chen, X. G., Huang, Y., Liu, Y., et al. (2015). Single nanoparticle to 3D supercage: Framing for an artiﬁcial enzyme system. Journal of the American Chemical Society, 137, 13957–13963. 39. Zhang, X. D., He, S. H., Chen, Z. H., & Huang, Y. M. (2013). CoFe2O4 nanoparticles as oxidase mimic-mediated chemiluminescence of aqueous luminol for sulﬁte in white wines. Journal of Agricultural and Food Chemistry, 61, 840–847. 40. Su, L., Qin, W. J., Zhang, H. G., Rahman, Z. U., Ren, C. L., Ma, S. D., et al. (2015). The peroxidase/catalase-like activities of MFe2O4 (M = Mg, Ni, Cu) MNPs and their application in colorimetric biosensing of glucose. Biosensors & Bioelectronics, 63, 384–391. 41. Fan, Y. W., Shi, W. B., Zhang, X. D., & Huang, Y. M. (2014). Mesoporous material-based manipulation of the enzyme-like activity of CoFe2O4 nanoparticles. Journal of Materials Chemistry A, 2, 2482–2486.

References

101

42. Yang, W., Hao, J., Zhang, Z., Lu, B., Zhang, B., & Tang, J. (2014). CoxFe3-xO4 hierarchical nanocubes as peroxidase mimetics and their applications in H2O2 and glucose detection. RSC Advances, 4, 35500–35504. 43. Abdolmohammad-Zadeh, H., & Rahimpour, E. (2015). A novel chemosensor for Ag(I) ion based on its inhibitory effect on the luminol-H2O2 chemiluminescence response improved by CoFe2O4 nanoparticles. Sensors and Actuators B-Chemical, 209, 496–504. 44. Kim, Y. S., & Jurng, J. (2013). A simple colorimetric assay for the detection of metal ions based on the peroxidase-like activity of magnetic nanoparticles. Sensors and Actuators B-Chemical, 176, 253–257. 45. Shi, W., Zhang, X., He, S., Li, J., & Huang, Y. (2013). Fast screening of the nanoparticles-based enzyme mimetics by a chemiluminescence method. Scientia Sinica Chimica, 43, 1591–1598. 46. Liu, S., Wang, L., Zhai, J. F., Luo, Y. L., & Sun, X. P. (2011). Carboxyl functionalized mesoporous polymer: A novel peroxidase-like catalyst for H2O2 detection. Analytical Methods, 3, 1475–1477. 47. Zhang, R. Z., He, S. J., Zhang, C. M., & Chen, W. (2015). Three-dimensional Fe- and N-incorporated carbon structures as peroxidase mimics for fluorescence detection of hydrogen peroxide and glucose. Journal of Materials Chemistry B, 3, 4146–4154. 48. Singh, A., Patra, S., Lee, J. A., Park, K. H., & Yang, H. (2011). An artiﬁcial enzyme-based assay: DNA detection using a peroxidase-like copper-creatinine complex. Biosensors & Bioelectronics, 26, 4798–4803. 49. Chen, X., Zhou, X. D., & Hu, J. M. (2012). Pt-DNA complexes as peroxidase mimetics and their applications in colorimetric detection of H2O2 and glucose. Analytical Methods, 4, 2183–2187. 50. Wang, J. J., Han, D. X., Wang, X. H., Qi, B., & Zhao, M. S. (2012). Polyoxometalates as peroxidase mimetics and their applications in H2O2 and glucose detection. Biosensors & Bioelectronics, 36, 18–21. 51. Li, Y., Li, X., Wong, Y.-S., Chen, T., Zhang, H., Liu, C., et al. (2011). The reversal of cisplatin-induced nephrotoxicity by selenium nanoparticles functionalized with 11-mercapto-1-undecanol by inhibition of ROS-mediated apoptosis. Biomaterials, 32, 9068–9076. 52. Li, Y., Li, X., Zheng, W., Fan, C., Zhang, Y., & Chen, T. (2013). Functionalized selenium nanoparticles with nephroprotective activity, the important roles of ROS-mediated signaling pathways. Journal of Materials Chemistry B, 1, 6365–6372. 53. Wang, W., Jiang, X. P., & Chen, K. Z. (2012). CePO4: Tb, Gd hollow nanospheres as peroxidase mimic and magnetic-fluorescent imaging agent. Chemical Communications, 48, 6839–6841. 54. Hu, P., Han, L., & Dong, S. (2014). A facile one-pot method to synthesize a polypyrrole/hemin nanocomposite and its application in biosensor, dye removal, and photothermal therapy. ACS Applied Materials & Interfaces, 6, 500–506. 55. Ryabov, A. D., Cerón-Camacho, R., Saavedra-Díaz, O., Denardo, M. A., Ghosh, A., Le Lagadec, R., et al. (2012). TAML activator-based amperometric analytical devices as alternatives to peroxidase biosensors. Analytical Chemistry, 84, 9096–9100. 56. Zhang, G.-Y., Deng, S.-Y., Cai, W.-R., Cosnier, S., Zhang, X.-J., & Shan, D. (2015). Magnetic zirconium hexacyanoferrate(ii) nanoparticle as tracing tag for electrochemical dna assay. Analytical Chemistry, 87, 9093–9100. 57. Tang, Y. R., Zhang, Y., Liu, R., Su, Y. Y., & Lu, Y. (2013). Application of NaYF4: Yb, Er nanoparticles as peroxidase mimetics in uric acid detection. Chinese Journal of Analytical Chemistry, 41, 330–336. 58. Sanchez-Sanchez, A., Arbe, A., Colmenero, J., & Pomposo, J. A. (2014). Metallo-folded single-chain nanoparticles with catalytic selectivity. ACS Macro Letters, 3, 439–443. 59. Tao, Y., Ju, E. G., Ren, J. S., & Qu, X. G. (2014). Polypyrrole nanoparticles as promising enzyme mimics for sensitive hydrogen peroxide detection. Chemical Communications, 50, 3030–3032.

102

5 Other Nanomaterials for Nanozymes

60. Liu, Y. J., Zhu, G. X., Yang, J., Yuan, A. H., & Shen, X. P. (2014). Peroxidase-like catalytic activity of Ag3PO4 nanocrystals prepared by a colloidal route. PLoS ONE, 9, 0109158. 61. Zhang, X. Q., Gong, S. W., Zhang, Y., Yang, T., Wang, C. Y., & Gu, N. (2010). Prussian blue modiﬁed iron oxide magnetic nanoparticles and their high peroxidase-like activity. Journal of Materials Chemistry, 20, 5110–5116. 62. Huang, Y., Lin, Y., Ran, X., Ren, J., & Qu, X. (2016). Self-assembly and compartmentalization of nanozymes in mesoporous silica-based nanoreactors. Chemistry—A European Journal, 22, 5705–5711. 63. Kong, J., Yu, X., Hu, W., Hu, Q., Shui, S., Li, L., et al. (2015). A biomimetic enzyme modiﬁed electrode for H2O2 highly sensitive detection. Analyst, 140, 7792–7798. 64. Lin, Y. H., Wu, L., Huang, Y. Y., Ren, J. S., & Qu, X. G. (2015). Positional assembly of hemin and gold nanoparticles in graphene-mesoporous silica nanohybrids for tandem catalysis. Chemical Science, 6, 1272–1276. 65. Liang, H., Jiang, S., Yuan, Q., Li, G., Wang, F., Zhang, Z., et al. (2016). Co-immobilization of multiple enzymes by metal coordinated nucleotide hydrogel nanoﬁbers: Improved stability and an enzyme cascade for glucose detection. Nanoscale, 8, 6071–6078. 66. Lin, Y. H., Li, Z. H., Chen, Z. W., Ren, J. S., & Qu, X. G. (2013). Mesoporous silica-encapsulated gold nanoparticles as artiﬁcial enzymes for self-activated cascade catalysis. Biomaterials, 34, 2600–2610. 67. Huang, Y. Y., Ran, X., Lin, Y. H., Ren, J. S., & Qu, X. G. (2015). Self-assembly of an organic-inorganic hybrid nanoflower as an efﬁcient biomimetic catalyst for self-activated tandem reactions. Chemical Communications, 51, 4386–4389.

Chapter 6

Challenges and Perspectives

Abstract The challenges and perspectives in the ﬁeld of nanozymes are summarized in this chapter, which if fully addressed, will lead to substantial breakthroughs in the future.

Keywords Nanozymes Artiﬁcial enzymes Enzyme mimics Catalytic nanomaterials Nanobiology Nanozymology Functional nanomaterials Biological catalysts Translational medicine Challenges and perspectives

As has been evidenced in the preceding chapters, highly active research interests have been devoted to the ﬁeld of nanozymes owing to their unique characteristics. Despite the remarkable progress has been made in the ﬁeld, the nanozyme research is still in its infancy. Therefore, substantial breakthroughs are expected, which will lead to the next wave of artiﬁcial enzymes for both fundamental science and practical applications by overcoming the following as well as other challenges [1–4]. (1) Nanozymes with new catalytic properties beyond redox enzyme mimics The currently developed nanozymes are mainly mimic redox enzymes (such as peroxidase, oxidase, catalase, and superoxide dismutase) and hydrolytic enzymes (such as nuclease, esterase) though other enzyme mimics have been reported [5, 6]. Given the fact that there are six major types of natural enzymes, future efforts should be focused on designing new nanozymes that may mimic their functionalities. More, as Professor Dr. Jean-Marie Lehn stated: “the chemist ﬁnds inspiration in the ingenuity of biological events and encouragement in the demonstration that such high efﬁciencies, selectivities, and rates can indeed be attained. However, chemistry is not limited to systems similar to those found in biology, but is free to create unknown species and to invent novel processes,” researchers are therefore encouraged to have great ambition to design new nanozymes beyond the natural ones [7].

© The Author(s) 2016 X. Wang et al., Nanozymes: Next Wave of Artiﬁcial Enzymes, SpringerBriefs in Molecular Science, DOI 10.1007/978-3-662-53068-9_6

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(2) Rational design of nanozymes The successful tackling of the above-mentioned challenge relies on our capability of rationally designing new nanozymes. To fulﬁll this goal, one should ﬁrst understand the nanozymes’ catalytic mechanisms both experimentally and theoretically [8–11]. Advanced characterization techniques, such as in situ (sub)atomic resolution TEM imaging and synchrotron spectroscopies, are expected to provide deeper insights. Recent progress in computational chemistry has allowed to design functional proteins (including enzymes), which should provide invaluable guidance to nanozyme design [12–14]. Despite the substantial progress in nanotechnology, it remains a great challenge to prepare uniform (especially the atomically uniform) nanomaterials. On the other hand, natural enzymes have well-deﬁned amino acid sequences (or nucleic acid sequences) as well as three-dimensional structures. Therefore, better synthetic strategies are still needed to prepare highly efﬁcient nanozymes with deﬁned sizes and structures even one may rationally design them in the future. For practical applications, large-scale synthesis of nanozymes is also expected in the near future. Industrial standards (and other necessary standards) should be established for both nanozymes’ synthesis and characterization. (3) Regulation of nanozymes’ activities In biological systems, enzymes’ activities are highly regulated. Inspired by this interesting phenomenon, numerous methods have been developed to tune the nanozymes’ activities [1, 15–17]. In nature, an enzyme’s activity could be tuned by regulating its expression and composition at genetic level and by controlling its surrounding environment and its interaction with speciﬁc ligands. All of these approaches should be exploited to regulate the nanozymes’ activities. For instance, in a cell, multiple enzymes usually work together within conﬁned compartments for synergetic cascade reactions. Recent studies demonstrated that nanozymes could also work cooperatively by co-assembling them together within conﬁned spaces [15]. To obtain highly efﬁcient nanozymes, the catalytic activities from both the core and the surface coating should be exploited. For the nanozymes with catalytically active core, the surface coating may shield their activities. Therefore, suitable coatings should be adopted. On the other hand, some nanozymes’ cores only acts as the supporting material. In this case, highly efﬁcient nanozymes could be obtained by exploring the synergistic activities of both the inorganic core and the surface coatings. Also by introducing chiral cores or surface coatings, nanozymes with chiral selectivities would be produced [18]. (4) Biosafety of nanozymes Both the dynamic and ﬁnal fates of nanozymes should be systematically studied at different levels to address the potential toxicity concerns [19–24]. For example, previous studies showed that the nanoparticles’ surface properties would affect their interaction with cell membrane and their subcellular localizations [25–27]. Biodistribution studies suggested that the nanozymes without targeting molecules

6 Challenges and Perspectives

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would accumulate mainly in liver, spleen, and lung [28, 29]. Other factors, like nanoparticles’ aspect ratio, may also affect their biodistributions [30]. Encouragingly, several studies showed that a few regulatory agencies approved that nanomaterials (such as Resovist (Ferucarbotran), i.e., the commercial available superparamagnetic iron oxide nanoparticles) have been used as nanozymes [31]. However, for most of the currently developed nanozymes, both their acute and long-term biosafety should be evaluated before they could be applied in clinics. (5) Translational promise of nanozymes As closely related with the biosafety issues discussed above, the potential applications of the nanozymes in translational medicine and clinics remain largely unexplored. Though the therapeutic effects of several nanozymes have been investigated, much more efforts are needed to translate the encouraging lab (and even pre-clinical) results into clinics to beneﬁt patients and the society [32]. (6) Beyond the catalysis Though it has suggested that redox active nanozymes showed promising neuroprotection and antioxidation effects via catalytic mechanisms, their applications deﬁnitely could be extended to other areas [33]. For instance, they could be used to modulate enzymes’ activities in vitro [34]. Overall, we believe that nanozymes will be widely adopted not only as highly efﬁcient biocatalysts but also as versatile tools in nanobiology, an interfaced area of nanotechnology, biology, biomedicine, etc. We and others have also speculated that nanozymes may even play a role in the early stages of life [2, 35].

References 1. Wei, H., & Wang, E. K. (2013). Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artiﬁcial enzymes. Chemical Society Reviews, 42, 6060–6093. 2. Wang, X. Y., Hu, Y. H., & Wei, H. (2016). Nanozymes in bionanotechnology: From sensing to therapeutics and beyond. Inorganic Chemistry Frontiers, 3, 41–60. 3. Kotov, N. A. (2010). Inorganic nanoparticles as protein mimics. Science, 330, 188–189. 4. Bornscheuer, U. T., Huisman, G. W., Kazlauskas, R. J., Lutz, S., Moore, J. C., & Robins, K. (2012). Engineering the third wave of biocatalysis. Nature, 485, 185–194. 5. Pieters, G., & Prins, L. J. (2012). Catalytic self-assembled monolayers on gold nanoparticles. New Journal of Chemistry, 36, 1931–1939. 6. Fillon, Y., Verma, A., Ghosh, P., Ernenwein, D., Rotello, V. M., & Chmielewski, J. (2007). Peptide ligation catalyzed by functionalized gold nanoparticles. Journal of the American Chemical Society, 129, 6676–6677. 7. Lehn, J. M. (2006). Supramolecular Chemistry: Concepts and Perspectives. Wiley-VCH: Weinheim. 8. Zhang, W., Hu, S. L., Yin, J. J., He, W. W., Lu, W., Ma, M., et al. (2016). Prussian blue nanoparticles as multienzyme mimetics and reactive oxygen species scavengers. Journal of the American Chemical Society, 5860–5865. 9. Shen, X., Liu, W., Gao, X., Lu, Z., Wu, X., & Gao, X. (2015). Mechanisms of oxidase and superoxide dismutation-like activities of gold, silver, platinum, and palladium, and their

106

10. 11.

12. 13. 14. 15.

16.

17.

18.

19.

20.

21.

22. 23.

24.

25.

26.

27.

28.

6 Challenges and Perspectives alloys: A general way to the activation of molecular oxygen. Journal of the American Chemical Society, 137, 15882–15891. Zhao, R., Zhao, X., & Gao, X. (2015). Molecular-level insights into intrinsic peroxidase-like activity of nanocarbon oxides. Chemistry-A European Journal, 21, 960–964. Ali, S. S., Hardt, J. I., & Dugan, L. L. (2008). SOD Activity of carboxyfullerenes predicts their neuroprotective efﬁcacy: A structure-activity study. Nanomedicine-Nanotechnology Biology and Medicine, 4, 283–294. Gonen, S., DiMaio, F., Gonen, T., & Baker, D. (2015). Design of ordered two-dimensional arrays mediated by noncovalent protein-protein interfaces. Science, 348, 1365–1368. Samish, I., MacDermaid, C. M., Perez-Aguilar, J. M., & Saven, J. G. (2011). Theoretical and computational protein design. Annual Review of Physical Chemistry, 62, 129–149. Lu, Y., Yeung, N., Sieracki, N., & Marshall, N. M. (2009). Design of functional metalloproteins. Nature, 460, 855–862. Cheng, H. J., Zhang, L., He, J., Guo, W. J., Zhou, Z. Y., Zhang, X. J., et al. (2016). Integrated nanozymes with nanoscale proximity for in vivo neurochemical monitoring in living brains. Analytical Chemistry, 88, 5489–5497. Tonga, G. Y., Jeong, Y., Duncan, B., Mizuhara, T., Mout, R., Das, R., et al. (2015). Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts. Nature Chemistry, 7, 597–603. Song, Y., Xu, C., Wei, W., Ren, J., & Qu, X. (2011). Light regulation of peroxidase activity by spiropyran functionalized carbon nanotubes used for label-free colorimetric detection of lysozyme. Chemical Communications, 47, 9083–9085. Chen, J. L.-Y., Pezzato, C., Scrimin, P., Prins, L. J. (2016). Chiral nanozymes–gold nanoparticle-based transphosphorylation catalysts capable of enantiomeric discrimination. Chemistry—A European Journal, 22, 7028–7032. Xia, T., Kovochich, M., Liong, M., Madler, L., Gilbert, B., Shi, H. B., et al. (2008). Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano, 2, 2121–2134. Minarchick, V. C., Stapleton, P. A., Porter, D. W., Wolfarth, M. G., Ciftyuerek, E., Barger, M., et al. (2013). Pulmonary cerium dioxide nanoparticle exposure differentially impairs coronary and mesenteric arteriolar reactivity. Cardiovascular Toxicology, 13, 323–337. An, Q., Sun, C. Y., Li, D., Xu, K., Guo, J., & Wang, C. C. (2013). Peroxidase-like activity of Fe3O4@carbon nanoparticles enhances ascorbic acid-induced oxidative stress and selective damage to PC-3 prostate cancer cells. ACS Applied Materials & Interfaces, 5, 13248–13257. See, V., Free, P., Cesbron, Y., Nativo, P., Shaheen, U., Rigden, D. J., et al. (2009). Cathepsin L digestion of nanobioconjugates upon endocytosis. ACS Nano, 3, 2461–2468. Wang, L. J., Min, Y., Xu, D. D., Yu, F. J., Zhou, W. Z., & Cuschieri, A. (2014). Membrane lipid peroxidation by the peroxidase-like activity of magnetite nanoparticles. Chemical Communications, 50, 11147–11150. Szymanski, C. J., Munusamy, P., Mihai, C., Xie, Y., Hu, D., Gilles, M. K., et al. (2015). Shifts in oxidation states of cerium oxide nanoparticles detected inside intact hydrated cells and organelles. Biomaterials, 62, 147–154. Vincent, A., Babu, S., Heckert, E., Dowding, J., Hirst, S. M., Inerbaev, T. M., et al. (2009). Protonated nanoparticle surface governing ligand tethering and cellular targeting. ACS Nano, 3, 1203–1211. Verma, A., Uzun, O., Hu, Y., Hu, Y., Han, H.-S., Watson, N., et al. (2008). Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nature Materials, 7, 588–595. Dowding, J. M., Das, S., Kumar, A., Dosani, T., McCormack, R., Gupta, A., et al. (2013). Cellular interaction and toxicity depend on physicochemical properties and surface modiﬁcation of redox-active nanomaterials. ACS Nano, 7, 4855–4868. Zhuang, J., Fan, K. L., Gao, L. Z., Lu, D., Feng, J., Yang, D. L., et al. (2012). Ex vivo detection of iron oxide magnetic nanoparticles in mice using their intrinsic peroxidase-mimicking activity. Molecular Pharmaceutics, 9, 1983–1989.

References

107

29. Rojas, S., Domingo Gispert, J., Abad, S., Buaki-Sogo, M., Garcia, H., & Raul Herance, J. (2012). In vivo biodistribution of amino-functionalized ceria nanoparticles in rats using positron emission tomography. Molecular Pharmaceutics, 9, 3543–3550. 30. Lin, S., Wang, X., Ji, Z., Chang, C. H., Dong, Y., Meng, H., et al. (2014). Aspect ratio plays a role in the hazard potential of CeO2 nanoparticles in mouse lung and zebraﬁsh gastrointestinal tract. ACS Nano, 8, 4450–4464. 31. Huang, D. M., Hsiao, J. K., Chen, Y. C., Chien, L. Y., Yao, M., Chen, Y. K., et al. (2009). The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticles. Biomaterials, 30, 3645–3651. 32. Dugan, L. L., Turetsky, D. M., Du, C., Lobner, D., Wheeler, M., Almli, C. R., et al. (1997). Carboxyfullerenes as neuroprotective agents. Proceedings of the National Academy of Sciences of the United States of America, 94, 9434–9439. 33. Dugan, L. L., Tian, L., Quick, K. L., Hardt, J. I., Karimi, M., Brown, C., et al. (2014). Carboxyfullerene neuroprotection postinjury in parkinsonian nonhuman primates. Annals of Neurology, 76, 393–402. 34. Huang, P.-J. J., Pautler, R., Shanmugaraj, J., Labbe, G., & Liu, J. (2015). Inhibiting the VIM-2 Metallo-β-Lactamase by graphene oxide and carbon nanotubes. ACS Applied Materials & Interfaces, 7, 9898–9903. 35. Prins, L. J. (2015). Emergence of complex chemistry on an organic monolayer. Accounts of Chemical Research, 48, 1920–1928.

Appendix

See Tables A.1, A.2 and A.3.

Table A.1 H2O2 detection with peroxidase mimics Nanozymes

Meth

Linear range

LOD

Comments

Ref.

Fe3O4 MNPs Fe3O4 MNPs

Color Color

5–100 μM 0.5–150.0 μM

3 μM 0.25 μM

[1] [2]

Fe3O4 MNPs

Color

1–100 μM

0.5 μM

Fe3O4 graphene oxide composites Fe-substituted SBA– 15 microparticles Iron phosphate microflowers [Fe(III) (biuret-amide)] on mesoporous silica FeTe nanorods Fe(III)-based coordination polymer Fe3O4 nanocomposites

Color

1–50 μM

0.32 μM

Substrate: ABTS Substrate: DPD H2O2 in rainwater, honey, and milk was tested Substrate: TMB Fe3O4 was encapsulated in mesoporous silica Substrate: TMB

Color

0.4–15 μM

0.2 μM

Substrate: TMB

[5]

Color

10–50 μM

10 nM

Substrate: TMB

[6]

Color

0.1–5 mM

10 μM

Substrate: TMB

[7]

Color Color

0.1–5 μM 1–50 μM

55 nM 0.4 μM

Substrate: ABTS Substrate: TMB

[8] [9]

Color

5–80 μM

1.07 μM

Substrate: TMB [10] Fe3O4 was functionalized by 5,10,15,20-Tetrakis (4-carboxyphenyl)porphyrin (continued)

© The Author(s) 2016 X. Wang et al., Nanozymes: Next Wave of Artiﬁcial Enzymes, SpringerBriefs in Molecular Science, DOI 10.1007/978-3-662-53068-9

[3]

[4]

109

110

Appendix

Table A.1 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

Protein-Fe3O4 and glucose oxidase nanocomposites GOx/Fe3O4/GO magnetic nanocomposite Iron(III) hydrogen phosphate hydrate crystals MIL-53(Fe)

Color

0.5–200 μM

0.2 μM

Substrate: TMB

[11]

Color

0.1–100 μM

0.04 μM

Substrate: DPD

[12]

Color

57.4–525.8 μM

1 μM

Substrate: TMB

[13]

Color

0.95–19 μM

0.13 μM

[14]

CuO NPs

Color

0.01–1mM

N/A

AuNPs

Color

18–1100 μM

4 μM

AuNC@BSA Au@Pt core/shell nanorods Nickel telluride nanowires Graphene oxide Hemin–graphene hybrid nanosheets Carbon nanodots Carbon nitride dots Tungsten carbide nanorods CoFe LDH nanoplates CoxFe3–xO4 nanocubes Porphyrin functionalized Co3O4 nanostructures Carboxyl functionalized mesoporous polymer PtPd nanodendrites on graphene nanosheets (PtPdNDs/GNs)

Color Color

0.5–20 μM 45–1000 μM

20 nM 45 μM

Substrate: TMB MIL-53(Fe): a metal– organic framework Substrate: 4-AAP and phenol Substrate: TMB Cysteamine was the ligand for AuNPs Substrate: TMB Substrate: OPD

Color

0.1–0.5 μM

25 nM

Substrate: ABTS

[19]

Color Color

0.05–100 μM 0.05–500 μM

50 nM 20 nM

Substrate: TMB Substrate: TMB

[20] [21]

Color Color Color

1–100 μM 1–100 μM 0.2–80 μM

0.2 μM 0.4 μM 60 nM

Substrate: TMB Substrate: TMB Substrate: TMB

[22] [23] [24]

Color

1–20 μM

0.4 μM

Substrate: TMB

[25]

Color.

1–60 μM

0.36 μM

Substrate: TMB

[26]

Color

1–75 μM

0.4 μM

Substrate: TMB

[27]

Color

1–8 μM

0.4 μM

Substrate: TMB

[28]

Color

0.5–150 μM

0.1 μM

Substrate: TMB

[29]

[15] [16]

[17] [18]

(continued)

Appendix

111

Table A.1 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

Pt-DNA complexes

Color

0.979–17.6 mM

0.392 mM

[30]

Manganese selenide nanoparticles Prussian blue nanoparticles MWCNTs-Prussian blue nanoparticles

Color

0.17–10 μM

0.085 μM

Substrate: TMB 3.92 μM was detected with PVDF membrane Substrate: TMB

Color

0.05–50 μM

0.031 μM

Substrate: ABTS

[32]

Color

1 μM–1.5 mM

100 nM

Polypyrrole nanoparticles

Color

5–100 μM

Polyoxometalate Polyoxometalate Fe3O4 MNPs

Color Color Fluor

1–20 μM 0.134–67 μM 10–200 nM

0.4 μM 0.134 μM 5.8 nM

BiFeO3 NPs

Fluor

20 nM–20 μM

4.5 nM

Fe3O4 MNPs

Fluor

0.18–900 μM

0.18 μM

Fe3O4 MNPs

Fluor

0.04–8 μM

0.008 μM

cupric oxide nanoparticles

Fluor

5–200 μM

0.34 μM

Substrate: TMB [33] Carbon nanotubes were ﬁlled with Prussian blue nanoparticles [34] Substrate: TMB PPy has been successfully employed to quantitatively monitor the H2O2 generated by macrophages Substrate: TMB [35] Substrate: TMB [36] Substrate: Rhodamine [37] B Fluorescence of Rhodamine B was quenched Substrate: BA [38] Oxidation of BA gave fluorescence H2O2 in rainwater was tested Fluorescence of [39] CdTe QD was quenched Substrate: BA [40] Oxidation of BA gave fluorescence Substrate: terephthalic [41] acid Terephthalic acid was oxidized by hydroxyl radical to form a highly fluorescent product (continued)

[31]

112

Appendix

Table A.1 (continued) Nanozymes

Meth

Linear range

LOD

Fe(III)–TAML activator CoFe2O4 NPs

CL

0.06–1 μM

0.05 μM

CL

0.1–4 μM

0.02 μM

CoFe2O4 NPs

CL

0.1–10 μM

10 nM

CoFe2O4 NPs with chitosan coating

CL

1 nM–4 μM

0.5 nM

Fe3O4 MNPs Fe3O4 microspheres-AgNP hybrids Fe3O4 MNPs

E-chem E-chem

4.2–800 μM 1.2–3500 μM

1.4 μM 1.2 μM

E-chem

0–16 nM

1.6 nM

Fe3O4 MNPs

E-chem

1–10 mM

N/A

Fe3O4 MNPs

E-chem

20–6250 μM

2.5 μM

Fe3O4 nanoﬁlms on TiN substrate

E-chem

1–700 μM

1 μM

Fe3O4 MNPs Fe3O4 MNPs

E-chem E-chem

0.2–2 mM 0.1–6 mM

0.01 mM 3.2 μM

Fe2O3 NPs Fe2O3 NPs

E-chem E-chem

20–140 μM 20–300 μM

11 μM 7 μM

Iron oxide NPs/CNT

E-chem

0.099–6.54 mM

53.6 μM

Comments

Ref. [42]

CoFe2O4 NPs form complexes with beta-CD H2O2 in natural water was tested CoFe2O4 NPs was coated with chitosan H2O2 in natural water was tested H2O2 in disinfected FBS samples was tested Fe3O4 was loaded on CNT Fe3O4 was entrapped in mesoporous carbon foam, and the composite was used to construct a carbon paste electrode Not a linear response Fe3O4 MNPs and PDDA–graphene formed multilayer via layer-by-layer assembly H2O2 in toothpaste was tested H2O2 in Walgreens antiseptic/oral debriding agent, Crest whitening mouthwash solution, Diet coke, and Gatorade was tested Fe3O4 was on reduced graphene oxide Fe2O3 was modiﬁed with Prussian blue.

[43]

[44] [45]

[46] [47]

[48] [49]

[50]

[51]

[52] [53] [54] [54]

[55] (continued)

Appendix

113

Table A.1 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

Fe3O4/self-reduced graphene nanocomposites

E-chem

0.001–20 mM

0.17 μM

Extracellular H2O2 released from HeLa cells stimulated by CdTe quantum dots (QDs) was established by this approach

[56]

FeS nanosheet FeS needle FeSe NPs FeS Co3O4 NPs Hemin–graphene hybrid nanosheets Layered double hydroxide–hemin nanocomposite Helical CNT LDH nanoflakes Calcined LDH CdS

E-chem E-chem E-chem E-chem E-chem E-chem

0.5–150 μM 5–140 μM 5–100 μM 10–130 μM 0.05–25 mM 0.5–400 μM

92 nM 4.3 μM 3.0 μM 4.03 μM 0.01 mM 0.2 μM

[57] [58] [58] [59] [60] [21]

E-chem

1–240 μM

0.3 μM

[61]

E-chem E-chem E-chem E-chem

0.5–115 μM 12–254 μM 1–100 μM 1–1900 μM

0.12 μM 2.3 μM 0.5 μM 0.28 μM

[62] [63] [64] [65]

Table A.2 Targets detection combining oxidases and peroxidase mimics Nanozymes

Meth

Linear range

LOD

Comments

Glucose Fe3O4 MNPs

Color

50–1000 μM

30 μM

Color

39–100 μM

30 μM

Substrate: ABTS [1] Selectivity against sugars: fructose, lactose, and maltose Substrate: ABTS [66] GOx was electrostatically assembled onto the Fe3O4@PDDA Glucose in serum samples was tested Compared with glucometer Selectivity against sugars: galactose, lactose, mannose, maltose, arabinose, cellobiose, rafﬁnose, and xylose (continued)

Fe3O4 MNPs with PDDA coating

Ref.

114

Appendix

Table A.2 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

Fe3O4 MNPs

Color

30–1000 μM

3 μM

[3]

Fe3O4 GO composites

Color

2–200 μM

0.74 μM

Fe3O4 nanocomposites

Color

5–25 μM

2.21 μM

Protein-Fe3O4 and glucose oxidase nanocomposites γ-Fe2O3 nanoparticles

Color

3–1000 μM

1.0 μM

Substrate: TMB Fe3O4 was encapsulated in mesoporous silica with GOx Showing the recycle capability Comparison between free MNPs versus encapsulated MNPs Substrate: TMB Glucose in urine was tested Substrate: TMB Fe3O4 was functionalized by 5,10,15,20-Tetrakis (4-carboxyphenyl)porphyrin Substrate: TMB

Color

1–80 μM

0.21 μM

GOx/Fe3O4/GO magnetic nanocomposite Graphite-like carbon nitrides

Color

0.5–600 μM

0.2 μM

Color

5–100 μM

0.1 μM

Iron oxide NPs

Color

31.2–250 μM

8.5 μM

Iron oxide NPs

Color

31.2–250 μM

15.8 μM

Iron oxide NPs

Color

0.12–4 μM

0.5 μM

Substrate: TMB Glucose in blood and urine was tested Substrate: DPD

[4]

[10]

[11]

[67]

[12]

Substrate: TMB [68] Glucose in serum was tested Substrate: ABTS [69] Iron oxide NPs was coated with glycine More robust than HRP towards NaN3 inhibition [69] Substrate: ABTS Iron oxide NPs was coated with heparin More robust than HRP towards NaN3 inhibition Substrate: ABTS [70] Iron oxide NPs was coated with APTES and MPTES (continued)

Appendix

115

Table A.2 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

ZnFe2O4

Color

1.25–18.75 μM

0.3 μM

[71]

[Fe(III) (biuret-amide)] on mesoporous silica FeTe nanorods

Color

20–300 μM

10 μM

Color

1–100 μM

0.38 μM

Fe(III)-based coordination polymer

Color

2–20 μM

1 μM

Mesoporous Fe2O3– graphene nanostructures CuO NPs

Color

0.5–10 μM

0.5 μM

Color

0.1–8 mM

N/A

V2O5 nanowires and Gold nanoparticles nanocomposite AuNPs

Color

0–10 μM

0.5 μM

Substrate: TMB Glucose in urine was tested Substrate: TMB Glucose in mice blood plasma was tested Substrate: ABTS Glucose in spiked blood was tested Substrate: TMB Glucose in serum was tested Substrate: TMB Glucose in serum was tested Substrate: 4-AAP and phenol Substrate: ABTS

Color

2.0–200 μM

0.5 μM

Au@Pt core/shell nanorods Nickel telluride nanowires Manganese selenide nanoparticles Graphene oxide

Color

45–400 μM

Color

[7]

[8]

[9]

[72]

[15] [73]

[16]

45 μM

Substrate: TMB Cysteamine was the ligand for AuNPs Substrate: OPD

1–50 μM

0.42 μM

Substrate: ABTS

[19]

Color

8–50 μM

1.6 μM

Substrate: TMB

[31]

Color

1–20 μM

1 μM

[20]

Graphene oxide

Color

2.5–5 mM

0.5 μM

Hemin–graphene hybrid nanosheets Carbon nanodots

Color

0.05–500 μM

30 nM

Substrate: TMB Glucose in blood and fruit juice was tested Substrate: TMB Graphene oxide was functionalized by chitosan Substrate: TMB

Color

1–500 μM

1 μM

Carbon nitride dots

Color

1–5 μM

0.5 μM

[18]

[74]

[21]

Substrate: TMB [22] Glucose in serum was tested Substrate: TMB [23] (continued)

116

Appendix

Table A.2 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

MWCNTs–Prussian blue nanoparticles

Color

1 μM–1 mM

200 nM

[33]

CoFe LDH nanoplates CoxFe3-xO4 nanocubes MoS2 nanosheets

Color

1–10 mM

0.6 μM

Substrate: TMB Carbon nanotubes were ﬁlled with Prussian blue nanoparticles Substrate: TMB

Color

8–90 μM

2.47 μM

Substrate: TMB

[26]

Color

5–150 μM

1.2 μM

[75]

Tungsten disulﬁde nanosheets

Color

5–300 μM

2.9 μM

Prussian blue nanoparticles Fe3O4 MNPs

Color

0.1–50 μM

0.03 μM

Substrate: TMB Glucose in serum was tested Substrate: TMB Glucose in serum of normal persons and diabetes persons was tested Substrate: ABTS

Fluor

1.6–160 μM

1.0 μM

Fe3O4 MNPs

Fluor

0.05–10 μM

0.025 μM

Fe3O4 MNPs with PDDA coating

Fluor

3–9 μM

3 μM

BiFeO3 NPs

Fluor

1–100 μM

0.5 μM

CoFe2O4 NPs

CL

0.1–10 μM

0.024 μM

[25]

[76]

[32]

Fluorescence of [39] CdTe QD was quenched Glucose in serum was tested Substrate: benzoic acid [40] Oxidation of BA gave fluorescence Glucose in serum was tested GOx was [77] electrostatically assembled onto the Fe3O4@PDDA Oxidation of AU gave fluorescence Glucose in serum was tested Selectivity against sugars: arabinose, cellobiose, galactose, lactose, maltose, rafﬁnose, and xylose Oxidation of BA gave [38] fluorescence Glucose in serum was tested Other sugars [44] (continued)

Appendix

117

Table A.2 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

CoFe2O4 NPs

CL

0.05–10 μM

10 nM

CoFe2O4 NPs were coated with chitosan Glucose in serum was tested

[45]

Hemin–graphene hybrid nanosheets Fe3O4 MNPs

E-chem

0.5–400 μM

0.3 μM

E-chem

6–2200 μM

6 μM

Fe3O4 MNPs

E-chem

0.5–10 mM

0.2 mM

Fe3O4–enzyme– polypyrrole nanoparticles Ascorbic acid MIL-53(Fe)

E-chem

0.5 μM– 34 mM

0.3 μM

Color

28.6–190.5 μM

15 μM

Substrate: TMB MIL-53(Fe): A Metal– Organic Framework

[14]

Dopamine CoxFe3-xO4 nanoparticles

Color

0.6–8 μM

0.13 μM

Substrate: TMB Dopamine in serum was tested

[80]

Thrombin Ag/Pt bimetallic nanoclusters

Color

1–50 nM

2.6 nM

Ag/Pt bimetallic nanoclusters was produced through a DNA-templated method

[81]

Color

1–100 μM

0.45 μM

Substrate: TMB

[82]

Color

1–80 μM

0.39 μM

Substrate: TMB

[82]

Glutathione Fe-MIL-88NH2 MOF Cysteine Fe-MIL-88NH2 MOF

[21] Glucose in serum was tested Compared with clinical analyzer Naﬁon for high selectivity against AA, UA, sucrose, and lactose Fe3O4 was encapsulated in mesoporous carbon with GOx, and the composite was used to construct a carbon paste electrode Comparison between free MNPs vs encapsulated MNPs Glucose in serum was tested

[78]

[49]

[79]

(continued)

118

Appendix

Table A.2 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

Color

1–80 μM

0.40 μM

Substrate: TMB

[82]

Fluor

20–100 μM

20 μM

[77]

Fe3O4 MNPs

E-chem

1 nM–10 mM (log)

0.1 nM

Platinum nanoparticles

Color

6–400 μM

2.5 μM

Choline oxidase was electrostatically assembled onto the Fe3O4@PDDA Oxidation of AU gave fluorescence Fe3O4 and choline oxidase were immobilized together on electrode Selectivity against AA and UA Substrate: N-ethyl-N(3-sulfopropyl)3-methylaniline sodium salt and 4-amino-antipyrine

Color

100 nM– 10 mM

39 nM

Substrate: TMB

[85]

Color

10–200 μM

2.84 μM

Substrate: N-ethyl-N(3-sulfopropyl)-3methylaniline sodium salt and 4-amino-antipyrine

[84]

Color

0–7 μM

0.3 μM

Substrate: TMB

[86]

Color

10–250 μM

5 μM

Substrate: TMB [3] Fe3O4 was encapsulated in mesoporous silica with cholesterol oxidase Showing the recycle capability Comparison between free MNPs versus encapsulated MNPs (continued)

Homocysteine Fe-MIL-88NH2 MOF Choline Fe3O4 MNPs with PDDA coating

Acetylcholine Fe3O4 nanospheres/reduced graphene oxide Platinum nanoparticles

Glutathione Carbon nanodots Cholesterol Fe3O4 MNPs

[83]

[84]

Appendix

119

Table A.2 (continued) Nanozymes

Meth

Linear range

LOD

Comments

Ref.

Au@Pt core/shell nanorods Galactose Fe3O4 MNPs

Color

30–300 μM

30 μM

Substrate: OPD

[18]

Color

10–200 mg/L

5 mg/L

[87]

Fluor

2–80 μM

2 μM

Substrate: ABTS Galactose in dried blood samples from normal persons and patients was tested Plates were used for sensing Galactose oxidase was electrostatically assembled onto the Fe3O4@PDDA Oxidation of AU gave fluorescence

Color

1–800 nM

0.2 nM

Substrate: TMB

[88]

Color

1–100 nM

4.52 nM

Substrate: TMB Gold nanoparticles were modiﬁed by kanamycin aptamer

[89]

Xanthine AuNC@BSA

Color

1–200 μM

0.5 μM

Substrate: TMB Xanthine in serum and urine samples was tested

[17]

Mercury(II) Ag nanoparticles

Color

0.5–800 nM

0.125 nM

[90]

Color Color

0–0.46 μM 0.01–4 nM

23 nM 8.5 pM

Substrate: TMB Mercury(II) in blood and wastewater was tested Substrate: TMB Substrate: TMB

E-chem

0.1–1 mM

4 μM

The calcium ion in a milk sample was tested

[93]

Fe3O4 MNPs with PDDA coating

Melamine Bare gold nanoparticles Kanamycin Gold nanoparticles

carbon nanodots Platinum Nanoparticle Calcium ion Co3O4 Nanomaterials

[77]

[91] [92]

120

Appendix

Table A.3 Nanozyme as peroxidase mimics for immunoassay Nanozyme

Target

Format

Fe3O4 NPs with dextran coating

PreS1

Antigen–down immunoassay Capture-detection sandwich immunoassay Antigen-down immunoassay Capture-detection sandwich immunoassay Sandwich immunoassay Antigen-down immunoassay

TnI

Fe3O4 NPs with chitosan coating

Mouse IgG CEA

CEA Fe2O3 NPs with Prussian blue coating Ferric nanocore residing in ferritin

Fe(1–x)MnxFe2O4 NPs with PMIDA coating MnFe2O4 NPs with citric acid coating Fe-TAML

Co3O4 nanoparticles Platinum nanoparticles Platinum Nanoparticles on Graphene Oxide Gold nanoparticles– graphene oxide hybrids Rod-shaped Au@PtCu

IgG

Avidin Nitrated human ceruloplasmin Mouse IgG

Comments

Ref. [94]

[95]

[96]

antigen-down immunoassay Sandwich immunoassay

Avidin-biotin interaction

[97]

Antigen-down immunoassay

Both direct and indirect assay

[98]

Sticholysin II

Antigen-down immunoassay

[99]

human IgG

Antigen-down immunoassay

vascular endothelial growth factor cytokeratin 19 fragments folate receptors

Antigen-down immunoassay

[101]

Sandwich immunoassay Antigen-down immunoassay

[102]

respiratory syncytial virus

Sandwich immunoassay

human IgG

Antigen-down immunoassay

Fe-TAML was encapsulated Inside Mesoporous Silica Nanoparticles

[100]

[103]

The peroxidase-like activity [104] of gold Nanoparticles–graphene oxide hybrids could be enhanced by mercury(II) The detection limit can be as [105] low as 90 pg/mL (continued)

Appendix

121

Table A.3 (continued) Nanozyme

Target

Format

Au@Pt nanorods with PSS coating Graphene oxide

mouse IL-2

Sandwich immunoassay Sandwich immunoassay

PSA

Comments

Ref. [106]

Clinical samples were tested

[107]

References 1. 2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

Wei, H., & Wang, E. (2008). Fe3O4 magnetic nanoparticles as peroxidase mimetics and their applications in H2O2 and glucose detection. Analytical Chemistry, 80, 2250–2254. Chang, Q., Deng, K. J., Zhu, L. H., Jiang, G. D., Yu, C., & Tang, H. Q. (2009). Determination of hydrogen peroxide with the aid of peroxidase-like Fe3O4 magnetic nanoparticles as the catalyst. Microchimica Acta, 165, 299–305. Kim, M. I., Shim, J., Li, T., Lee, J., & Park, H. G. (2011). Fabrication of nanoporous nanocomposites entrapping Fe3O4 magnetic nanoparticles and oxidases for colorimetric biosensing. Chemistry-A European Journal, 17, 10700–10707. Dong, Y. L., Zhang, H. G., Rahman, Z. U., Su, L., Chen, X. J., Hu, J., et al. (2012). Graphene oxide-Fe3O4 magnetic nanocomposites with peroxidase-like activity for colorimetric detection of glucose. Nanoscale, 4, 3969–3976. Liu, S., Tian, J. Q., Wang, L., Luo, Y. L., Chang, G. H., & Sun, X. P. (2011). Iron-substituted SBA-15 microparticles: A peroxidase-like catalyst for H2O2 detection. Analyst, 136, 4894–4897. Wang, S., Chen, W., Liu, A. L., Hong, L., Deng, H. H., & Lin, X. H. (2012). Comparison of the peroxidase-like activity of unmodiﬁed, amino-modiﬁed, and citrate-capped gold nanoparticles. ChemPhysChem, 13, 1199–1204. Malvi, B., Panda, C., & Dhar, B. B. (2012). Sen Gupta, S. One pot glucose detection by [Fe-III(biuret-amide)] immobilized on mesoporous silica nanoparticles: An efﬁcient HRP mimic. Chemical Communications, 48, 5289–5291. Roy, P., Lin, Z. H., Liang, C. T., & Chang, H. T. (2012). Synthesis of enzyme mimics of iron telluride nanorods for the detection of glucose. Chemical Communications, 48, 4079– 4081. Tian, J. Q., Liu, S., Luo, Y. L., & Sun, X. P. (2012). Fe(III)-based coordination polymer nanoparticles: Peroxidase-like catalytic activity and their application to hydrogen peroxide and glucose detection. Catalysis Science & Technology, 2, 432–436. Liu, Q. Y., Li, H., Zhao, Q. R., Zhu, R. R., Yang, Y. T., Jia, Q. Y., et al. (2014). Glucose-sensitive colorimetric sensor based on peroxidase mimics activity of porphyrin-Fe3O4 nanocomposites. Materials Science & Engineering C-Materials for Biological Applications, 41, 142–151. Liu, Y., Yuan, M., Qiao, L. J., & Guo, R. (2014). An efﬁcient colorimetric biosensor for glucose based on peroxidase-like protein-Fe3O4 and glucose oxidase nanocomposites. Biosensors & Bioelectronics, 52, 391–396. Chang, Q., & Tang, H. Q. (2014). Optical determination of glucose and hydrogen peroxide using a nanocomposite prepared from glucose oxidase and magnetite nanoparticles immobilized on graphene oxide. Microchimica Acta, 181, 527–534. Zhang, T. B., Lu, Y. C., & Luo, G. S. (2014). Synthesis of hierarchical iron hydrogen phosphate crystal as a robust peroxidase mimic for stable H2O2 detection. ACS Applied Materials & Interfaces, 6, 14433–14438.

122

Appendix

14.

Ai, L. H., Li, L. L., Zhang, C. H., Fu, J., & Jiang, J. (2013). MIL-53(Fe): A metal-organic framework with intrinsic peroxidase-like catalytic activity for colorimetric biosensing. Chemistry-A European Journal, 19, 15105–15108. Chen, W., Chen, J., Feng, Y. B., Hong, L., Chen, Q. Y., Wu, L. F., et al. (2012). Peroxidase-like activity of water-soluble cupric oxide nanoparticles and its analytical application for detection of hydrogen peroxide and glucose. Analyst, 137, 1706–1712. Jv, Y., Li, B. X., & Cao, R. (2010). Positively-charged gold nanoparticles as peroxidiase mimic and their application in hydrogen peroxide and glucose detection. Chemical Communications, 46, 8017–8019. Wang, X. X., Wu, Q., Shan, Z., & Huang, Q. M. (2011). BSA-stabilized Au clusters as peroxidase mimetics for use in xanthine detection. Biosensors & Bioelectronics, 26, 3614– 3619. Liu, J. B., Hu, X. N., Hou, S., Wen, T., Liu, W. Q., Zhu, X., et al. (2012). Au@Pt core/shell nanorods with peroxidase- and ascorbate oxidase-like activities for improved detection of glucose. Sensors and Actuators B-Chemical, 166, 708–714. Wan, L. J., Liu, J. H., & Huang, X. J. (2014). Novel magnetic nickel telluride nanowires decorated with thorns: Synthesis and their intrinsic peroxidase-like activity for detection of glucose. Chemical Communications, 50, 13589–13591. Song, Y. J., Qu, K. G., Zhao, C., Ren, J. S., & Qu, X. G. (2010). Graphene oxide: Intrinsic peroxidase catalytic activity and its application to glucose detection. Advanced Materials, 22, 2206–2210. Guo, Y. J., Li, J., & Dong, S. J. (2011). Hemin functionalized graphene nanosheets-based dual biosensor platforms for hydrogen peroxide and glucose. Sensors and Actuators B-Chemical, 160, 295–300. Shi, W. B., Wang, Q. L., Long, Y. J., Cheng, Z. L., Chen, S. H., Zheng, H. Z., et al. (2011). Carbon nanodots as peroxidase mimetics and their applications to glucose detection. Chemical Communications, 47, 6695–6697. Liu, S., Tian, J. Q., Wang, L., Luo, Y. L., & Sun, X. P. (2012). A general strategy for the production of photoluminescent carbon nitride dots from organic amines and their application as novel peroxidase-like catalysts for colorimetric detection of H2O2 and glucose. RSC Advances, 2, 411–413. Li, N., Yan, Y., Xia, B. Y., Wang, J. Y., & Wang, X. (2014). Novel tungsten carbide nanorods: An intrinsic peroxidase mimetic with high activity and stability in aqueous and organic solvents. Biosensors & Bioelectronics, 54, 521–527. Zhang, Y. W., Tian, J. Q., Liu, S., Wang, L., Qin, X. Y., Lu, W. B., et al. (2012). Novel application of CoFe layered double hydroxide nanoplates for colorimetric detection of H2O2 and glucose. Analyst, 137, 1325–1328. Yang, W. S., Hao, J. H., Zhang, Z., Lu, B. P., Zhang, B. L., & Tang, J. L. (2014). CoxFe3-xO4 hierarchical nanocubes as peroxidase mimetics and their applications in H2O2 and glucose detection. RSC Advances, 4, 35500–35504. Liu, Q. Y., Zhu, R. R., Du, H., Li, H., Yang, Y. T., Jia, Q. Y., et al. (2014). Higher catalytic activity of porphyrin functionalized Co3O4 nanostructures for visual and colorimetric detection of H2O2 and glucose. Materials Science & Engineering C-Materials for Biological Applications, 43, 321–329. Liu, S., Wang, L., Zhai, J. F., Luo, Y. L., & Sun, X. P. (2011). Carboxyl functionalized mesoporous polymer: A novel peroxidase-like catalyst for H2O2 detection. Analytical Methods, 3, 1475–1477. Chen, X. M., Su, B. Y., Cai, Z. X., Chen, X., & Oyama, M. (2014). PtPd nanodendrites supported on graphene nanosheets: A peroxidase-like catalyst for colorimetric detection of H2O2. Sensors and Actuators B-Chemical, 201, 286–292. Chen, X., Zhou, X. D., & Hu, J. M. (2012). Pt-DNA complexes as peroxidase mimetics and their applications in colorimetric detection of H2O2 and glucose. Analytical Methods, 4, 2183–2187.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

Appendix 31.

32.

33.

34.

35.

36.

37.

38.

39.

40. 41.

42.

43.

44.

45.

46.

47.

123

Qiao, F. M., Chen, L. J., Li, X. N., Li, L. F., & Ai, S. Y. (2014). Peroxidase-like activity of manganese selenide nanoparticles and its analytical application for visual detection of hydrogen peroxide and glucose. Sensors and Actuators B-Chemical, 193, 255–262. Zhang, W. M., Ma, D., & Du, J. X. (2014). Prussian blue nanoparticles as peroxidase mimetics for sensitive colorimetric detection of hydrogen peroxide and glucose. Talanta, 120, 362–367. Wang, T., Fu, Y. C., Chai, L. Y., Chao, L., Bu, L. J., Meng, Y., et al. (2014). Filling carbon nanotubes with prussian blue nanoparticles of high peroxidase- like catalytic activity for colorimetric chemo and biosensing. Chemistry-A European Journal, 20, 2623–2630. Tao, Y., Ju, E. G., Ren, J. S., & Qu, X. G. (2014). Polypyrrole nanoparticles as promising enzyme mimics for sensitive hydrogen peroxide detection. Chemical Communications, 50, 3030–3032. Liu, M., Zhao, H. M., Chen, S., Yu, H. T., & Quan, X. (2012). Stimuli-responsive peroxidase mimicking at a smart graphene interface. Chemical Communications, 48, 7055– 7057. Wang, J. J., Han, D. X., Wang, X. H., Qi, B., & Zhao, M. S. (2012). Polyoxometalates as peroxidase mimetics and their applications in H2O2 and glucose detection. Biosensors & Bioelectronics, 36, 18–21. Jiang, Z. L., Kun, L., Ouyang, H. X., Liang, A. H., & Jiang, H. S. (2011). A simple and sensitive fluorescence quenching method for the determination of H2O2 using rhodamine B and Fe3O4 nanocatalyst. Journal of Fluorescence, 21, 2015–2020. Luo, W., Li, Y. S., Yuan, J., Zhu, L. H., Liu, Z. D., Tang, H. Q., et al. (2010). Ultrasensitive fluorometric determination of hydrogen peroxide and glucose by using multiferroic BiFeO3 nanoparticles as a catalyst. Talanta, 81, 901–907. Gao, Y., Wang, G. N., Huang, H., Hu, J. J., Shah, S. M., & Su, X. G. (2011). Fluorometric method for the determination of hydrogen peroxide and glucose with Fe3O4 as catalyst. Talanta, 85, 1075–1080. Shi, Y., Su, P., Wang, Y. Y., & Yang, Y. (2014). Fe3O4 peroxidase mimetics as a general strategy for the fluorescent detection of H2O2-involved systems. Talanta, 130, 259–264. Hu, A. L., Liu, Y. H., Deng, H. H., Hong, G. L., Liu, A. L., Lin, X. H., et al. (2014). Fluorescent hydrogen peroxide sensor based on cupric oxide nanoparticles and its application for glucose and L-lactate detection. Biosensors & Bioelectronics, 61, 374–378. Vdovenko, M. M., Demiyanova, A. S., Kopylov, K. E., & Sakharov, I. Y. (2014). Fe-III-TAML activator: A potent peroxidase mimic for chemiluminescent determination of hydrogen peroxide. Talanta, 125, 361–365. He, S. H., Shi, W. B., Zhang, X. D., Li, J. A., & Huang, Y. M. (2010). β-cyclodextrins-based inclusion complexes of CoFe2O4 magnetic nanoparticles as catalyst for the luminol chemiluminescence system and their applications in hydrogen peroxide detection. Talanta, 82, 377–383. Shi, W. B., Zhang, X. D., He, S. H., & Huang, Y. M. (2011). CoFe2O4 magnetic nanoparticles as a peroxidase mimic mediated chemiluminescence for hydrogen peroxide and glucose. Chemical Communications, 47, 10785–10787. Fan, Y. W., & Huang, Y. M. (2012). The effective peroxidase-like activity of chitosan-functionalized CoFe2O4 nanoparticles for chemiluminescence sensing of hydrogen peroxide and glucose. Analyst, 137, 1225–1231. Zhang, L. H., Zhai, Y. M., Gao, N., Wen, D., & Dong, S. J. (2008). Sensing H2O2 with layer-by-layer assembled Fe3O4-PDDA nanocomposite ﬁlm. Electrochemistry Communications, 10, 1524–1526. Liu, Z. L., Zhao, B., Shi, Y., Guo, C. L., Yang, H. B., & Li, Z. A. (2010). Novel nonenzymatic hydrogen peroxide sensor based on iron oxide-silver hybrid submicrospheres. Talanta, 81, 1650–1654.

124

Appendix

48.

Kang, S. Z., Chen, H., & Mu, J. (2011). Electrodes modiﬁed with multiwalled carbon nanotubes carrying Fe3O4 beads: High sensitivity to H2O2. Solid State Sciences, 13, 142– 145. Kim, M. I., Ye, Y., Won, B. Y., Shin, S., Lee, J., & Park, H. G. (2011). A highly efﬁcient electrochemical biosensing platform by employing conductive nanocomposite entrapping magnetic nanoparticles and oxidase in mesoporous carbon foam. Advanced Functional Materials, 21, 2868–2875. Liu, X. X., Zhu, H., & Yang, X. R. (2011). An amperometric hydrogen peroxide chemical sensor based on graphene-Fe3O4 multilayer ﬁlms modiﬁed ITO electrode. Talanta, 87, 243–248. Yang, J., Xiang, H., Shuai, L., & Gunasekaran, S. (2011). A sensitive enzymeless hydrogen-peroxide sensor based on epitaxially-grown Fe3O4 thin ﬁlm. Analytica Chimica Acta, 708, 44–51. Zhang, Z. X., Zhu, H., Wang, X. L., & Yang, X. R. (2011). Sensitive electrochemical sensor for hydrogen peroxide using Fe3O4 magnetic nanoparticles as a mimic for peroxidase. Microchimica Acta, 174, 183–189. Ye, Y. P., Kong, T., Yu, X. F., Wu, Y. K., Zhang, K., & Wang, X. P. (2012). Enhanced nonenzymatic hydrogen peroxide sensing with reduced graphene oxide/ferroferric oxide nanocomposites. Talanta, 89, 417–421. Dutta, A. K., Maji, S. K., Srivastava, D. N., Mondal, A., Biswas, P., Paul, P., et al. (2012). Peroxidase-like activity and amperometric sensing of hydrogen peroxide by Fe2O3 and prussian blue-modiﬁed Fe2O3 nanoparticles. Journal of Molecular Catalysis A-Chemical, 360, 71–77. Miao, Y. Q., Wang, H., Shao, Y. Y., Tang, Z. W., Wang, J., & Lin, Y. H. (2009). Layer-by-layer assembled hybrid ﬁlm of carbon nanotubes/iron oxide nanocrystals for reagentless electrochemical detection of H2O2. Sensors and Actuators B-Chemical, 138, 182–188. Fang, H. T., Pan, Y. L., Shan, W. Q., Guo, M. L., Nie, Z., Huang, Y., et al. (2014). Enhanced nonenzymatic sensing of hydrogen peroxide released from living cells based on Fe3O4/self-reduced graphene nanocomposites. Analytical Methods, 6, 6073–6081. Dai, Z. H., Liu, S. H., Bao, J. C., & Ju, H. X. (2009). Nanostructured FeS as a mimic peroxidase for biocatalysis and biosensing. Chemistry-A European Journal, 15, 4321– 4326. Dutta, A. K., Maji, S. K., Srivastava, D. N., Mondal, A., Biswas, P., Paul, P., et al. (2012). Synthesis of FeS and FeSe nanoparticles from a single source precursor: A study of their photocatalytic activity, peroxidase-like behavior, and electrochemical sensing of H2O2. ACS Applied Materials & Interfaces, 4, 1919–1927. Maji, S. K., Dutta, A. K., Biswas, P., Srivastava, D. N., Paul, P., Mondal, A., et al. (2012). Synthesis and characterization of FeS nanoparticles obtained from a dithiocarboxylate precursor complex and their photocatalytic, electrocatalytic and biomimic peroxidase behavior. Applied Catalysis A-General, 419, 170–177. Mu, J. S., Wang, Y., Zhao, M., & Zhang, L. (2012). Intrinsic peroxidase-like activity and catalase-like activity of Co3O4 nanoparticles. Chemical Communications, 48, 2540–2542. Zhang, F. T., Long, X., Zhang, D. W., Sun, Y. L., Zhou, Y. L., Ma, Y. R., et al. (2014). Layered double hydroxide-hemin nanocomposite as mimetic peroxidase and its application in sensing. Sensors and Actuators B-Chemical, 192, 150–156. Cui, R. J., Han, Z. D., & Zhu, J. J. (2011). Helical carbon nanotubes: Intrinsic peroxidase catalytic activity and its application for biocatalysis and biosensing. Chemistry-A European Journal, 17, 9377–9384. Wang, Y. L., Chen, S. H., Ni, F., Gao, F., & Li, M. G. (2009). Peroxidase-like layered double hydroxide nanoflakes for electrocatalytic reduction of H2O2. Electroanalysis, 21, 2125–2132.

49.

50.

51.

52.

53.

54.

55.

56.

57.

58.

59.

60. 61.

62.

63.

Appendix 64.

65.

66.

67.

68.

69.

70.

71.

72.

73.

74.

75.

76.

77. 78.

79.

125

Cui, L., Yin, H. S., Dong, J., Fan, H., Liu, T., Ju, P., et al. (2011). A mimic peroxidase biosensor based on calcined layered double hydroxide for detection of H2O2. Biosensors & Bioelectronics, 26, 3278–3283. Maji, S. K., Dutta, A. K., Srivastava, D. N., Paul, P., Mondal, A., & Adhikary, B. (2012). Peroxidase-like behavior, amperometric biosensing of hydrogen peroxide and photocatalytic activity by cadmium sulﬁde nanoparticles. Journal of Molecular Catalysis A-Chemical, 358, 1–9. Yu, C. J., Lin, C. Y., Liu, C. H., Cheng, T. L., & Tseng, W. L. (2010). Synthesis of poly (diallyldimethylammonium chloride)-coated Fe3O4 nanoparticles for colorimetric sensing of glucose and selective extraction of thiol. Biosensors & Bioelectronics, 26, 913–917. Mitra, K., Ghosh, A. B., Sarkar, A., Saha, N., & Dutta, A. K. (2014). Colorimetric estimation of human glucose level using gamma-Fe2O3 nanoparticles: An easily recoverable effective mimic peroxidase. Biochemical and Biophysical Research Communications, 451, 30–35. Lin, T. R., Zhong, L. S., Wang, J., Guo, L. Q., Wu, H. Y., Guo, Q. Q., et al. (2014). Graphite-like carbon nitrides as peroxidase mimetics and their applications to glucose detection. Biosensors & Bioelectronics, 59, 89–93. Yu, F. Q., Huang, Y. Z., Cole, A. J., & Yang, V. C. (2009). The artiﬁcial peroxidase activity of magnetic iron oxide nanoparticles and its application to glucose detection. Biomaterials, 30, 4716–4722. Liu, Y. P., & Yu, F. Q. (2011). Substrate-speciﬁc modiﬁcations on magnetic iron oxide nanoparticles as an artiﬁcial peroxidase for improving sensitivity in glucose detection. Nanotechnology, 22, 145704. Su, L., Feng, J., Zhou, X. M., Ren, C. L., Li, H. H., & Chen, X. G. (2012). Colorimetric detection of urine glucose based ZnFe2O4 magnetic nanoparticles. Analytical Chemistry, 84, 5753–5758. Xing, Z. C., Tian, J. Q., Asiri, A. M., Qusti, A. H., Al-Youbi, A. O., & Sun, X. P. (2014). Two-dimensional hybrid mesoporous Fe2O3-graphene nanostructures: A highly active and reusable peroxidase mimetic toward rapid, highly sensitive optical detection of glucose. Biosensors & Bioelectronics, 52, 452–457. Qu, K. G., Shi, P., Ren, J. S., & Qu, X. G. (2014). Nanocomposite incorporating V2O5 nanowires and gold nanoparticles for mimicking an enzyme cascade reaction and its application in the detection of biomolecules. Chemistry-A European Journal, 20, 7501– 7506. Wang, G. L., Xu, X. F., Wu, X. M., Cao, G. X., Dong, Y. M., & Li, Z. J. (2014). Visible-light-stimulated enzymelike activity of graphene oxide and its application for facile glucose sensing. Journal of Physical Chemistry C, 118, 28109–28117. Lin, T. R., Zhong, L. S., Guo, L. Q., Fu, F. F., & Chen, G. N. (2014). Seeing diabetes: Visual detection of glucose based on the intrinsic peroxidase-like activity of MoS2 nanosheets. Nanoscale, 6, 11856–11862. Lin, T. R., Zhong, L. S., Song, Z. P., Guo, L. Q., Wu, H. Y., Guo, Q. Q., et al. (2014). Visual detection of blood glucose based on peroxidase-like activity of WS2 nanosheets. Biosensors & Bioelectronics, 62, 302–307. Liu, C. H., & Tseng, W. L. (2011). Oxidase-functionalized Fe3O4 nanoparticles for fluorescence sensing of speciﬁc substrate. Analytica Chimica Acta, 703, 87–93. Yang, L. Q., Ren, X. L., Tang, F. Q., & Zhang, L. (2009). A practical glucose biosensor based on Fe3O4 nanoparticles and chitosan/naﬁon composite ﬁlm. Biosensors & Bioelectronics, 25, 889–895. Yang, Z. P., Zhang, C. J., Zhang, J. X., & Bai, W. B. (2014). Potentiometric glucose biosensor based on core-shell Fe3O4-enzyme-polypyrrole nanoparticles. Biosensors & Bioelectronics, 51, 268–273.

126

Appendix

80.

Niu, X. Y., Xu, Y. Y., Dong, Y. L., Qi, L. Y., Qi, S. D., Chen, H. L., et al. (2014). Visual and quantitative determination of dopamine based on CoxFe3-xO4 magnetic nanoparticles as peroxidase mimetics. Journal of Alloys and Compounds, 587, 74–81. Zheng, C., Zheng, A. X., Liu, B., Zhang, X. L., He, Y., Li, J., et al. (2014). One-pot synthesized DNA-templated Ag/Pt bimetallic nanoclusters as peroxidase mimics for colorimetric detection of thrombin. Chemical Communications, 50, 13103–13106. Jiang, Z. W., Liu, Y., Hu, X. O., & Li, Y. F. (2014). Colorimetric determination of thiol compounds in serum based on Fe-MIL-88NH(2) metal-organic framework as peroxidase mimetics. Analytical Methods, 6, 5647–5651. Zhang, Z. X., Wang, X. L., & Yang, X. R. (2011). A sensitive choline biosensor using Fe3O4 magnetic nanoparticles as peroxidase mimics. Analyst, 136, 4960–4965. He, S. B., Wu, G. W., Deng, H. H., Liu, A. L., Lin, X. H., Xia, X. H., et al. (2014). Choline and acetylcholine detection based on peroxidase-like activity and protein antifouling property of platinum nanoparticles in bovine serum albumin scaffold. Biosensors & Bioelectronics, 62, 331–336. Qian, J., Yang, X. W., Jiang, L., Zhu, C. D., Mao, H. P., & Wang, K. (2014). Facile preparation of Fe3O4 nanospheres/reduced graphene oxide nanocomposites with high peroxidase-like activity for sensitive and selective colorimetric detection of acetylcholine. Sensors and Actuators B-Chemical, 201, 160–166. Shamsipur, M., Safavi, A., & Mohammadpour, Z. (2014). Indirect colorimetric detection of glutathione based on its radical restoration ability using carbon nanodots as nanozymes. Sensors and Actuators B-Chemical, 199, 463–469. Kim, M. I., Shim, J., Li, T., Woo, M. A., Cho, D., Lee, J., et al. (2012). Colorimetric quantiﬁcation of galactose using a nanostructured multi-catalyst system entrapping galactose oxidase and magnetic nanoparticles as peroxidase mimetics. Analyst, 137, 1137–1143. Ni, P. J., Dai, H. C., Wang, Y. L., Sun, Y. J., Shi, Y., Hu, J. T., et al. (2014). Visual detection of melamine based on the peroxidase-like activity enhancement of bare gold nanoparticles. Biosensors & Bioelectronics, 60, 286–291. Sharma, T. K., Ramanathan, R., Weerathunge, P., Mohammadtaheri, M., Daima, H. K., Shukla, R., et al. (2014). Aptamer-mediated ‘turn-off/turn-on’ nanozyme activity of gold nanoparticles for kanamycin detection. Chemical Communications, 50, 15856–15859. Sun, Z. Z., Zhang, N., Si, Y. M., Li, S., Wen, J. W., Zhu, X. B., et al. (2014). High-throughput colorimetric assays for mercury(II) in blood and wastewater based on the mercury-stimulated catalytic activity of small silver nanoparticles in a temperature-switchable gelatin matrix. Chemical Communications, 50, 9196–9199. Mohammadpour, Z., Safavi, A., & Shamsipur, M. (2014). A new label free colorimetric chemosensor for detection of mercury ion with tunable dynamic range using carbon nanodots as enzyme mimics. Chemical Engineering Journal, 255, 1–7. Wu, G. W., He, S. B., Peng, H. P., Deng, H. H., Liu, A. L., Lin, X. H., et al. (2014). Citrate-capped platinum nanoparticle as a smart probe for ultrasensitive mercury sensing. Analytical Chemistry, 86, 10955–10960. Mu, J. S., Zhang, L., Zhao, M., & Wang, Y. (2014). Catalase mimic property of Co3O4 nanomaterials with different morphology and its application as a calcium sensor. ACS Applied Materials & Interfaces, 6, 7090–7098. Gao, L. Z., Zhuang, J., Nie, L., Zhang, J. B., Zhang, Y., Gu, N., et al. (2007). Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nature Nanotechnology, 2, 577– 583. Gao, L. Z., Wu, J. M., Lyle, S., Zehr, K., Cao, L. L., & Gao, D. (2008). Magnetite nanoparticle-linked immunosorbent assay. Journal of Physical Chemistry C, 112, 17357– 17361.

81.

82.

83. 84.

85.

86.

87.

88.

89.

90.

91.

92.

93.

94.

95.

Appendix 96.

97.

98.

99.

100.

101.

102.

103.

104.

105.

106.

107.

127

Zhang, X. Q., Gong, S. W., Zhang, Y., Yang, T., Wang, C. Y., & Gu, N. (2010). Prussian blue modiﬁed iron oxide magnetic nanoparticles and their high peroxidase-like activity. Journal of Materials Chemistry, 20, 5110–5116. Tang, Z. W., Wu, H., Zhang, Y. Y., Li, Z. H., & Lin, Y. H. (2011). Enzyme-mimic activity of ferric nano-core residing in ferritin and its biosensing applications. Analytical Chemistry, 83, 8611–8616. Bhattacharya, D., Baksi, A., Banerjee, I., Ananthakrishnan, R., Maiti, T. K., & Pramanik, P. (2011). Development of phosphonate modiﬁed Fe(1-x)MnxFe2O4 mixed ferrite nanoparticles: Novel peroxidase mimetics in enzyme linked immunosorbent assay. Talanta, 86, 337–348. Figueroa-Espi, V., Alvarez-Paneque, A., Torrens, M., Otero-Gonzalez, A. J., & Reguera, E. (2011). Conjugation of manganese ferrite nanoparticles to an anti Sticholysin monoclonal antibody and conjugate applications. Colloids and Surfaces A-Physicochemical and Engineering Aspects, 387, 118–124. Kumari, S., Dhar, B. B., Panda, C., & Meena, A. (2014). Sen Gupta, S. Fe-TAML encapsulated inside mesoporous silica nanoparticles as peroxidase mimic: Femtomolar protein detection. ACS Applied Materials & Interfaces, 6, 13866–13873. Dong, J. L., Song, L. N., Yin, J. J., He, W. W., Wu, Y. H., Gu, N., et al. (2014). Co3O4 nanoparticles with multi-enzyme activities and their application in immunohistochemical assay. ACS Applied Materials & Interfaces, 6, 1959–1970. Song, Y. J., Xia, X. F., Wu, X. F., Wang, P., & Qin, L. D. (2014). Integration of platinum nanoparticles with a volumetric bar-chart chip for biomarker assays. Angewandte Chemie-International Edition, 53, 12451–12455. Zhang, L. N., Deng, H. H., Lin, F. L., Xu, X. W., Weng, S. H., Liu, A. L., et al. (2014). In situ growth of porous platinum nanoparticles on graphene oxide for colorimetric detection of cancer cells. Analytical Chemistry, 86, 2711–2718. Zhan, L., Li, C. M., Wu, W. B., & Huang, C. Z. (2014). A colorimetric immunoassay for respiratory syncytial virus detection based on gold nanoparticles-graphene oxide hybrids with mercury-enhanced peroxidase-like activity. Chemical Communications, 50, 11526– 11528. Hu, X. N., Saran, A., Hou, S., Wen, T., Ji, Y. L., Liu, W. Q., et al. (2014). Rod-shaped Au@PtCu nanostructures with enhanced peroxidase-like activity and their ELISA application. Chinese Science Bulletin, 59, 2588–2596. He, W. W., Liu, Y., Yuan, J. S., Yin, J. J., Wu, X. C., Hu, X. N., et al. (2011). Au@Pt nanostructures as oxidase and peroxidase mimetics for use in immunoassays. Biomaterials, 32, 1139–1147. Qu, F. L., Li, T., & Yang, M. H. (2011). Colorimetric platform for visual detection of cancer biomarker based on intrinsic peroxidase activity of graphene oxide. Biosensors & Bioelectronics, 26, 3927–3931.

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