Toxicology of Nanomaterials

This book provides the reader with a comprehensive view of analytical methods for nanotoxicology studies. After an introduction to nanomaterials and toxicological studies, the book discusses various characterization methods of nanomaterials and continues with the detection of nanoparticles in vivo as well as in vitro. A variety of techniques in molecular toxicology of nanomaterials is presented, followed by a detailed explanation of interaction between nanoparticles and biomacromolecules, including the structure-toxicity relationships of nanomaterials. Finally, the book concludes with the advantages and challenges of the analytical methods for nanotoxicology.

Zhiyong Zhang holds a PhD in radiochemistry from Beijing University, China. He is a professor and a scientific leader in environment health and safety at the Chinese Academy of Sciences in the Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety. His current research interests are in coordination chemistry, bioinorganic chemistry, and environmental chemistry of rare earth elements, as well as toxicology and ecotoxicology of nanomaterials.

Weiyue Feng graduated from Fudan University of Applied Chemistry, China, in 1989 and received her PhD from the Institute of High Energy Physics, Chinese Academy of Sciences, in 1998. She is currently professor of inorganic chemistry and biological chemistry. Her primary fields of research include chemical biology, metallomics and metalloproteins as well as biological and toxicological studies of nanomaterials.

Yuliang Zhao is Professor in Chemistry and Physics. He moved to Chinese Academy of Sciences from RIKEN, Japan, as a Hundred Elite Professor in 2001. His research is mainly focused on the biomedical effects of nanostructures and nanoscale materials, including the biomedical functions of nanomaterials, the toxicological effects of nanomaterials and establishing standard procedures for safety assessment of nanoproducts, surface chemistry of nanoparticles and their novel properties, and molecular dynamics using theoretical simulation of the dynamic processes of the interplay between nanosystems and biosystems.

List of Contributors XV

Preface XIX

Abbreviations XXI

1 Characterization of Nanomaterials in Nanotoxicological Analyses 1
Yuhui Ma

1.1 Introduction 1

1.2 Size and Morphology of NMs 2

1.3 Composition and Structure 8

1.4 Surface Properties 12

1.5 Interactions between NMs and Biological Environments 15

1.6 Conclusions 16

References 16

2 Quantitative Analysis of Metal-Based Nanomaterials in Biological Samples Using ICP-MS 23
Meng Wang

2.1 Introduction 23

2.2 ICP-MS: A Power Tool for Element Analysis 24

2.3 Single-Particle ICP-MS: Theory and Application 28

2.4 Analysis of Nanoparticles by ICP-MS Hyphenate Techniques 33

2.5 Conclusion and Outlook 38

References 38

3 Stable Isotopic Tracing of Nanomaterials In Vivo 43
Yuliang Zhao and Xueling Chang

3.1 Introduction 43

3.2 Development of Stable Isotope Labeling in Nanotechnology 45

3.3 13C-Labeled Carbon Nanomaterials 46

3.4 Metal Stable Isotope Labeled Nanoparticles 56

3.5 Summary and Outlook 61

References 61

4 Radiolabeling of Nanoparticles 69
Zhiyong Zhang

4.1 Introduction 69

4.2 Radiolabeling of Nanomaterials 74

4.3 Summary and Outlook 87

References 88

5 New Methods for Nanotoxicity Analyses: Synchrotron-Radiation-Based Techniques 95
Bing Wang

5.1 Introduction 95

5.2 Speciation Transformation of NMs in Biological System by SR-Based Techniques 96

5.3 SR-Based Analytical Techniques for Understanding Nano–Bio Interactions 103

5.4 Conclusion and Prospects 115

References 116

6 Imaging Techniques in Nanotoxicology Research 121
Liang Yan, Yufeng Li, and Zhanjun Gu

6.1 Introduction 121

6.2 Imaging Techniques for In Vitro Visualization and Quantification of Nanomaterials 121

6.3 Distribution and Quantification of Nanomaterials In Vivo 133

6.4 Conclusions 139

References 141

7 In Vivo Nanotoxicity Assays in Animal Models 151
Xiao He

7.1 Introduction 151

7.2 Laboratory Animal Models 152

7.3 Administration 158

7.4 Particokinetics 166

7.5 In Vivo Toxicity of Nanomaterials 174

7.6 Recommendations 182

References 183

8 In Vitro Testing Methods for Nanomaterials 199
Feng Zhao and Xueying Liu

8.1 Introduction 199

8.2 Preparation of Nanoparticle Suspensions 200

8.3 Cell Viability Assays 201

8.4 Oxidative Stress Assay 204

8.5 Inflammatory Assay 205

8.6 Summary and Outlook 207

References 208

9 Localizing the Cellular Uptake of Nanomaterials 211
Wei Li

9.1 Introduction 211

9.2 Mechanism of Cellular Uptake of Nanomaterials 212

9.3 Methods to Determine Cellular Nanoparticle Uptake In Vitro 213

9.4 Representative Cellular Uptake of Nanomaterials and Intracellular Location Determined with Different Methods 217

9.5 Summary and Outlook 227

References 227

10 Methods and Techniques in Molecular Toxicology of Nanomaterials 231
Yanli Wang, Chenchen Li, and Chunying Chen

10.1 Introduction 231

10.2 Gene Mutation Detection 232

10.3 Gene Expression Analysis 235

10.4 DNA Damage Detection 238

10.5 Chromosomal Aberration Analysis 242

10.6 Omics 246

10.7 Conclusions 247

References 247

11 Analyses Methods for Nanoparticle Interaction with Biomacromolecules 257
Liming Wang and Chunying Chen

11.1 Introduction 257

11.2 Biological Effects due to Nanoparticle–Biomolecule Interactions 258

11.3 Basic Methods to Understand NPs and Protein Interactions 267

11.4 Summary and Outlook 280

References 281

12 "Omic" Techniques for Nanosafety 287
Weiyue Feng

12.1 Introduction 287

12.2 Materials and Biological Models 289

12.3 Genomics Study for Nanosafety 290

12.4 Transcriptomics Study for the Biological Effects of ENMs 297

12.5 Proteomics Study for Nanosafety 303

12.6 Metabolomics Study for Nanosafety 310

12.7 Summary and Outlook 313

References 314

13 Nanometallomics: New Approach on Analyzing Biological Effects of Metal-Related Nanomaterials 319
Yu-Feng Li, Jiating Zhao, Yuxi Gao, and Chunying Chen

13.1 Introduction 319

13.2 Integrated Approaches on the ADME of Metal-Related Nanomaterials in Biological Systems 320

13.3 Interactions of Metal-Related Nanomaterials with Genes, Proteins, and Other Biomolecules 325

13.4 Conclusions 328

Acknowledgments 328

References 328

14 Molecular Simulation Methods for Safety Analyses of Nanomaterials 333
Lina Zhao

14.1 Introduction 333

14.2 The Molecular Simulation Methods for Nanomaterials and Biological Systems 335

14.3 The Scientific Problems in Biological Effects of Nanomaterials Studied by Molecular Simulations 352

14.4 Summary and Outlook 361

Acknowledgments 361

References 362

15 Ecotoxicity Analyses of Nanomaterials 367
Peng Zhang

15.1 Introduction 367

15.2 Transformation of ENMs in the Environment 368

15.3 Toxicity of ENMs in Terrestrial Ecosystem 370

15.4 Other Terrestrial Organisms 379

15.5 Aquatic Organisms 382

15.6 Challenges and Perspective 384

References 384

Index 393

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Toxicology of Nanomaterials

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