Biomedical Applications and Toxicology of Carbon Nanomaterials

Biomedical Applications and Toxicology of Carbon Nanomaterials

By: Haifang Wang (author), Chunying Chen (author)Hardback

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Description

An overview of biomedical applications and the toxicity properties of carbon nanomaterials aimed at helping to avoid detrimental health effects while laying the groundwork for further research in this highly relevant field. Summarizing recent research, the book starts with the synthesis and functionalization of carbon nanomaterials, as well as identification and detection in biosystems. It then moves on to the interaction between carbon nanoparticles and biocomponents, focusing on the toxicity and mechanisms to various organs and systems and potential biomedical applications as well. Each section highlights the challenges, outlines unanswered questions, and suggests directions for further research and development efforts.

About Author

Chunying Chen is principal investigator in the Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety at the National Center for Nanoscience and Technology of China. She obtained her PhD degree in biomedical engineering from Huazhong University of Science and Technology of China. Chunying Chen has authored and co-authored more than 150 peer-reviewed papers, 3 books and 6 book chapters, has 12 issued patents and one international standard. She has been awarded the National Award for Innovation and Outstanding Service to the Standard authorized by Standardization Administration of the People's Republic of China in 2011, the Second Prize of Beijing Science and Technology in 2008, the Second Prize of the National Natural Science Award in 2012, the National Science Fund for Distinguished Young Scholars, and China Outstanding Young Female Scientists Awards in 2014. Haifang Wang is professor in the Institute of Nanochemistry and Nanobiology at the Shanghai University. She received her BSc and MSc degrees in chemistry from Fudan University and PhD degree in chemistry from Peking University. From 1994 to 2008, she was a faculty at Peking University. As a visiting scholar, she spent one year at the Institute of Physical and Chemical Research (RIKEN), Japan and one year at Clemson University, USA. In 2009, she moved to Shanghai University. She is the editorial board member of Nanomedicine (Lond.) and the standing committee member of Nanotoxicology Committee, Chinese Society of Toxicology. She has published over 120 scientific papers and book chapters, and was awarded the Second Prize of the National Natural Science Award in 2012 (third place).

Contents

List of Contributors XIX Preface XXV 1 Synthesis, Functionalization, and Characterization 1 Jianxun Xu, Xing Lu, and Baowen Li 1.1 Introduction 1 1.2 Fullerenes and Metallofullerenes 1 1.2.1 Synthesis and Purification 2 1.2.1.1 Synthesis 2 1.2.1.2 Purification 2 1.2.2 Chemical Functionalization 3 1.2.2.1 Carbene Reaction 3 1.2.2.2 Bingel Hirsch Reaction 4 1.2.2.3 Prato Reaction 5 1.2.2.4 Bis-Silylation 5 1.2.2.5 Diels Alder Reaction and Benzyne Reaction 5 1.2.2.6 Singly Bonded Addition 6 1.2.2.7 Supramolecular Complexes of EMFs 6 1.2.3 Characterization 6 1.2.3.1 Synchrotron Radiation Powder Diffraction (SRPD)/Rietveld/MEM 6 1.2.3.2 Nuclear Magnetic Resonance (NMR) Spectroscopy 7 1.2.3.3 Theoretical Calculation 7 1.2.3.4 Single-Crystal X-ray Diffraction Crystallography 7 1.2.3.5 Others 8 1.2.4 Questions and Future Directions 8 1.3 Carbon Nanotubes 8 1.3.1 Synthesis 9 1.3.1.1 Arc Discharge Method 9 1.3.1.2 Laser Ablation Method 10 1.3.1.3 CVD Method 10 1.3.1.4 Synthesis of CNTs with a Defined Structure 10 1.3.2 Functionalization 11 1.3.2.1 Covalent Chemical Reactions 11 1.3.2.2 Noncovalent Modifications 11 1.3.3 Characterization 12 1.3.3.1 Microscopic Characterizations 12 1.3.3.2 Spectroscopic Characterizations 13 1.3.4 Questions and Future Directions 13 1.4 Graphene 14 1.4.1 Synthesis and Characterization 14 1.4.2 Functionalization of Graphene and Graphene Oxide 17 1.4.3 Prospects and Challenges 18 1.5 Summary and Outlook 20 References 21 2 Identification and Detection of Carbon Nanomaterials in Biological Systems 29 Haifang Wang, Zheng-Mei Song, Yi-Fan Yang, Aoneng Cao, and Yuanfang Liu 2.1 Introduction 29 2.2 Available Techniques for Qualitative and Quantitative Determination 30 2.2.1 Optical Microscopic Observation 30 2.2.2 Electron Microscopic (EM) Observation 31 2.2.3 Raman Spectroscopic Measurement 33 2.2.4 Fluorescence Analysis 36 2.2.4.1 Intrinsic Fluorescence Analysis 36 2.2.4.2 Labeled Fluorescence Analysis 39 2.2.5 Isotope Labeling Method 39 2.2.5.1 Radioisotope Labeling 40 2.2.5.2 Stable Isotope Labeling 43 2.2.5.3 Tips for Isotopic Labeling 43 2.2.6 Chromatographic Technique 45 2.2.7 Flow Cytometry Method 45 2.2.8 Other Methods 46 2.3 Summary and Outlook 47 Acknowledgments 48 References 48 3 Biodistribution and Pharmacokinetics of Carbon Nanomaterials In Vivo 55 Sheng-Tao Yang, Xiaoyang Liu, and Jingru Xie 3.1 Introduction 55 3.2 Amorphous Carbon Nanoparticles 55 3.2.1 Ultrafine Carbon Particles 56 3.2.2 Carbon Nanoparticles 58 3.2.3 Carbon Dots 59 3.3 sp2 Carbon Nanomaterials 62 3.3.1 Fullerene 62 3.3.2 Carbon Nanotubes 69 3.3.3 Carbon Nanohorns 77 3.3.4 Graphene 80 3.3.5 Graphene Quantum Dots 85 3.4 Nanodiamonds 87 3.5 Summary and Outlook 89 Acknowledgments 90 References 90 4 Interaction of Carbon Nanomaterials and Components in Biological Systems 97 Jian Tian and Cuicui Ge 4.1 Introduction 97 4.2 Factors Affecting Interaction 99 4.2.1 Characteristics of Carbon Nanomaterials 99 4.2.1.1 Size and Layer 99 4.2.1.2 Surface Modification and Functionalization 100 4.2.2 Biological Microenvironment 102 4.2.2.1 pH 103 4.2.2.2 Ionic Strength 104 4.2.2.3 Weak Interactions 104 4.2.2.4 Cell Selectivity 105 4.3 Interaction of Carbon Nanomaterials with Various Components in Biological Systems 107 4.3.1 Characterization and Methodology of Interaction of Carbon Nanomaterials with Components in the Biological System 107 4.3.2 Carbon Nanomaterial Phospholipid Interaction 108 4.3.3 Carbon Nanomaterial Protein Interaction 111 4.3.4 Carbon Nanomaterial DNA Interaction 115 4.3.5 Carbon Nanomaterial Cell Interaction 119 4.4 Conclusion and Perspectives 120 References 122 5 Biomedical Applications of Carbon Nanomaterials 131 Liangzhu Feng and Zhuang Liu 5.1 Introduction 131 5.2 Biomedical Applications of Fullerenes 132 5.2.1 Fullerenes as Antioxidants and Neuroprotective Agents 132 5.2.2 Fullerenes as Antitumor Agents 134 5.2.3 Metallofullerenes as MRI Contrast Agent 136 5.2.4 Fullerenes for Other Applications 136 5.3 Biomedical Applications of Carbon Nanotubes 137 5.3.1 Carbon Nanotubes for Drug Delivery 138 5.3.1.1 Carbon Nanotubes for the Delivery of Small Drug Molecules 139 5.3.1.2 Carbon Nanotubes for the Delivery of Biomacromolecules 141 5.3.2 Carbon Nanotubes for Photothermal and Combined Therapies of Tumors 142 5.3.2.1 Carbon Nanotubes for PhotothermalTherapy of Tumors 142 5.3.2.2 Carbon Nanotubes for CombinedTherapies of Tumors 143 5.3.3 Carbon Nanotubes for Bioimaging 144 5.3.3.1 Carbon Nanotubes for Fluorescence Imaging 144 5.3.3.2 Carbon Nanotubes for Raman Imaging 145 5.3.3.3 Carbon Nanotubes for Photoacoustic Imaging 145 5.3.3.4 Carbon Nanotubes for Other Bioimaging Modalities 145 5.3.4 Carbon Nanotubes for Other Biomedical Applications 146 5.4 Biomedical Applications of Graphene 146 5.4.1 Graphene for Drug Delivery 147 5.4.1.1 Graphene for the Delivery of Small Drug Molecules 148 5.4.1.2 Graphene for the Delivery of Biomacromolecules 148 5.4.2 Graphene for Photothermal and CombinedTherapies of Tumors 151 5.4.3 Graphene for Bioimaging 152 5.4.4 Graphene for Other Biomedical Applications 153 5.5 Conclusion and Perspectives 153 Acknowledgments 154 References 155 6 Pulmonary Effects of Carbon Nanomaterials 163 Liying Wang, Donna C. Davidson, Vincent Castranova, and Yon Rojanasakul 6.1 Introduction 163 6.2 Physicochemical Properties of Carbon Nanomaterials 164 6.2.1 Types of Carbon Nanomaterials 165 6.2.2 Effects of Size 165 6.2.3 Effects of Agglomeration State 166 6.2.4 Aspect Ratio Considerations 168 6.2.5 Surface Modifications 168 6.3 Fate of Pulmonary Exposed Carbon Nanoparticles (Deposition, Distribution, Translocation, and Clearance) 169 6.3.1 Deposition and Distribution of Carbon Nanoparticles in the Lung 169 6.3.2 Translocation of Carbon Nanoparticles 172 6.3.3 Clearance of Carbon Nanomaterials from the Lungs 175 6.4 Carbon Nanomaterial Induced Lung Responses 176 6.4.1 Key/Specific Target Lung Cell Types of Pulmonary-Exposed Carbon Nanoparticles 176 6.4.2 Lung Inflammation 178 6.4.3 Immune Response 179 6.4.4 Fibrosis 180 6.4.5 Genotoxicity 181 6.4.6 Cancer 182 6.4.7 Cardiovascular Effects Following Pulmonary Exposure of Carbon Nanomaterials 184 6.5 Summary 184 Disclaimer 184 References 189 7 Cardiovascular and Hemostatic Effects of Carbon Nanomaterials 195 Xiaoyong Deng, Cheng Li, Jiajun Wang, and Pan Chen 7.1 Background 195 7.2 Carbon Nanotubes 195 7.2.1 Hemotoxicity of CNTs 196 7.2.1.1 What Is Hemotoxicity 196 7.2.1.2 Complement System 197 7.2.1.3 Red Blood Cells 199 7.2.1.4 Hemostatic System and Coagulation/Thrombosis/Atheroma 200 7.2.2 Effects on Cardiovascular System 201 7.3 Fullerenes 203 7.3.1 Fullerenes Escape from Lungs into Circulation 203 7.3.2 Toxicity of Fullerenes on the Cardiovascular System 204 7.4 Graphene-Related Nanomaterials 205 7.5 Conclusions and Outlook 208 Acknowledgments 208 References 208 8 Modulation of the Immune System by Fullerene and Graphene Derivatives 213 Ligeng Xu and Chunying Chen 8.1 Introduction 213 8.2 The Immunological Effects of Fullerene and Its Derivatives 213 8.2.1 Fullerene Derivatives Can Inhibit Inflammation via Blocking ROS Generation 213 8.2.2 Fullerene Derivatives Promote Immune Responses via Modulating Macrophages and/or Antigen Presenting Cells (APCs) 215 8.3 Immunological Effects of Graphene and Its Derivatives 222 8.3.1 Immunological Effect of Pristine Graphene 225 8.3.2 Immunological Effects of Graphene Oxide and Its Derivatives 227 8.4 Perspectives and Outlook 231 References 234 9 Neuro-, Hepato-, and Nephrotoxicity of Carbon-based Nanomaterials 239 Jia Yao and Yongbin Zhang 9.1 Carbon-based Nanomaterials: Introduction 239 9.2 Neurotoxicity of Carbon-based Nanomaterials 240 9.2.1 Blood Brain Barrier and BBB Penetration by Carbon-based Nanomaterials 240 9.2.2 Neurotoxicity of Carbon Nanotubes 241 9.2.3 Strategies to Reduce Neurotoxicity of Carbon Nanotubes 243 9.2.4 Neurotoxicity of Other Carbon-based Nanomaterials 244 9.3 Hepato and Nephrotoxicity of Carbon-based Nanomaterials 245 9.3.1 Carbon Nanotube Biodistribution in the Liver and Kidney 245 9.3.2 Biodistribution of Other Carbon Nanomaterials 248 9.3.3 Hepatotoxicity of Carbon Nanotubes 251 9.3.4 Carbon Nanotube Nephrotoxicity/Renal Toxicity 254 9.3.5 Hepatotoxicity and Nephrotoxicity of Other Types of Carbon-based Nanomaterials 254 9.4 Points of Consideration for Toxicity Evaluation of Carbon-based Nanomaterials 257 9.5 Summary 259 Acknowledgments 259 References 259 10 Genotoxicity and Carcinogenic Potential of Carbon Nanomaterials 267 Todd A. Stueckle, Linda Sargent, Yon Rojanasakul, and Liying Wang 10.1 Introduction 267 10.1.1 Engineered Nanomaterials and Long-Term Disease Risk: An Introduction 269 10.1.2 Carcinogenesis: A Multistep Process 270 10.1.2.1 Genotoxicity and Initiation 271 10.1.2.2 Promotion 272 10.1.2.3 Progression 274 10.1.3 Current Knowledge and Challenges in Carcinogenesis Studies 274 10.2 Carbon Nanomaterials: Genotoxicity and Carcinogenic Potential 275 10.2.1 Physicochemical Properties of ECNMs 275 10.2.2 Ultrafine Carbon Black 276 10.2.2.1 In Vivo Studies 277 10.2.2.2 In Vitro Studies 278 10.2.3 Carbon Nanotubes 278 10.2.3.1 In Vivo Studies 279 10.2.3.2 In Vitro Studies 291 10.2.4 Fullerenes and Derivatives 296 10.2.4.1 In Vivo Studies 297 10.2.4.2 In Vitro Studies 299 10.2.5 Graphene and Graphene Oxide 300 10.2.5.1 In Vivo Studies 302 10.2.5.2 In Vitro Studies 304 10.2.6 Carbon Nanofibers and Other Particles 307 10.2.6.1 In Vivo Studies 307 10.2.6.2 In Vitro Studies 308 10.3 Future Challenges in Carbon Nanomaterial Carcinogenesis Risk Assessment 308 10.3.1 Exposure Characterization and Fate 308 10.3.2 Dosimetry 309 10.3.3 Model Choice 310 10.3.4 Systematic Evaluation of Genotoxicity 311 10.3.5 Role of ROS and Inflammation 311 10.4 Assessment of ECNM-Induced Genotoxicity and Carcinogenesis 312 10.4.1 Recommendations for Screening ENMs for Carcinogenic Potential 312 10.4.2 Systematic Screening Paradigm and Workflow for ENM Carcinogenicity Risk Assessment 314 10.5 Concluding Remarks 316 Acknowledgments 316 Disclaimer 316 References 317 11 Effect on Reproductive System of Carbon Nanomaterials 333 Ying Liu and Chunying Chen 11.1 Introduction 333 11.2 Effects of Carbon Nanomaterials on the Reproductive System 334 11.2.1 Carbon Nanotubes 335 11.2.2 Fullerene Derivatives 340 11.2.3 Carbon Black Nanoparticles 340 11.3 Insights into the Molecular Mechanisms 342 11.3.1 Potential Toxicity to the Female Reproductive System 342 11.3.2 Potential Toxicity to Male Reproduction of Carbon Nanomaterials 343 11.3.3 Potential Toxicity to Offspring of Carbon Nanomaterials 345 11.3.4 Impact on the Endocrine Organs and Hormone Biosynthesis/Metabolism 346 11.3.5 Others 348 11.4 Conclusion and Perspectives 348 Acknowledgments 352 References 352 12 Immunological Responses Induced by Carbon Nanotubes Exposed to Skin and Gastric and Intestinal System 357 Haiyan Xu, JieMeng, Qiang Ma, and Xiaojin Li 12.1 Introduction 357 12.2 Biological Effects of CNTs by Dermal Exposure 358 12.2.1 In Vitro Assessment in Dermal-Related Cell Lines 358 12.2.2 In Vivo Studies on the Responses Elicited by Skin Exposed with CNTs 361 12.3 Immunological Reactions Elicited by Subcutaneous Administration of MWCNTs 362 12.3.1 Preparation and Characterization of Multiwalled Carbon Nanotubes for Uses in Studies 362 12.3.2 Distribution of Subcutaneously Injected Carbon Nanotubes 363 12.3.3 Immunological Responses Induced by Subcutaneously Injected MWCNTs 369 12.3.3.1 Macrophages Responses Exerted by MWCNTs 370 12.3.3.2 MWCNTs Attract Naive Monocyte Macrophages Through Activating Macrophages in the Subcutis 373 12.3.3.3 Subcutaneously Injected MWCNTs Induce Complement Activation 375 12.3.3.4 Subcutaneously Injected MWCNTs Elevate Pro-inflammatory Cytokines in the Blood 376 12.4 Immunological Responses Induced by Subcutaneous Administration of MWCNTs in Tumor-Bearing Mice 377 12.4.1 MWCNTs Induce Systematic Immune Responses in Tumor-Bearing Mice 378 12.4.2 MWCNTs Upregulate Multiple Pro-inflammatory Cytokines in the Blood 378 12.4.3 MWCMTs Mediate Cytotoxicity of Lymphocytes 379 12.4.4 MWCNTs Induce Complement Activation 380 12.4.5 MWCNTs Attract Monocyte-Macrophages to Affect the Microenvironment of Tumor Mass 380 12.5 CNTs as Antigen Delivery System to Enhance Immune Responses Against Tumors 383 12.6 Immunological Responses of Gastric and Intestinal Systems Exposed to Carbon Nanotubes 386 References 389 13 Modulation of Immune System by Carbon Nanotubes 397 Marit Ilves and Harri Alenius 13.1 Immune System 397 13.1.1 Innate Immunity Cells and Their Main Functions 398 13.1.2 Adaptive Immunity Cells andTheir Main Functions 399 13.2 Carbon Nanotubes (CNTs) and Innate Immunity 400 13.2.1 Complement Activation 401 13.2.2 Macrophages 402 13.2.3 Activation of Inflammasome Complex and IL-1 Secretion 405 13.2.4 Neutrophils 406 13.2.5 Innate Lymphoid Cells (ILCs) 408 13.2.6 Dendritic Cells 408 13.3 CNTs and Adaptive Immunity 409 13.3.1 The Effects of CNTs on Vaccine Delivery and Immunotherapy 409 13.3.2 Utilization of CNT Scaffolds in the Expanding and Modulation of Immune Cells 411 13.3.3 Immunosuppressive Effects of CNTs 413 13.4 The Effect of CNTs in Allergy and Asthma 414 13.4.1 Allergic Reactions and Their Immunological Mechanisms 414 13.4.2 Asthma 415 13.4.3 Allergic Pulmonary Inflammation Induced by Airway Exposure to CNTs 417 13.4.4 Modulation of Allergen-Induced Airway Inflammation by Exposure to CNTs 418 13.4.5 CNT in the Context of Mast Cells and Eosinophils 420 13.4.6 Role of IL-33 Pathway in CNT-Induced Allergic Responses 420 13.5 Conclusions and Future Prospects 422 References 424 14 Carbon Dots: Synthesis, Bioimaging, and Biosafety Assessment 429 Jie Wang and Yao He 14.1 Introduction 429 14.1.1 Synthesis and Fabrication of C-dots 429 14.1.2 Bioimaging of C-dots 431 14.1.3 Biosafety Assessment of C-dots 432 14.2 Synthetic Strategies 433 14.2.1 Microwave-Assisted Methods 433 14.2.2 Hydrothermal Carbonization 434 14.2.3 Electrochemical Synthesis 437 14.2.4 Chemical Oxidation 439 14.2.5 Ultrosonication 442 14.2.6 Plasma Treatment 444 14.2.7 Laser Ablation Methods 445 14.2.8 Supported Methods 446 14.2.9 Thermal Routes 448 14.3 C-Dots-based Fluorescent Probes for Bioimaging Applications 450 14.3.1 Fluorescent Probes for Bioimaging Applications 450 14.3.2 In Vitro Imaging 451 14.3.3 In Vivo Imaging 456 14.3.4 Conclusion 462 14.4 Toxicity Assessment 462 14.4.1 In Vitro Toxicity Assessment 463 14.4.2 In Vivo Toxicity Assessment 469 14.4.3 Conclusion 475 14.5 Perspectives 477 14.5.1 Unequivocal PL Mechanism 477 14.5.2 Expanding the Spectral Coverage 478 14.5.3 QY Improvement 478 14.5.4 Bioimaging 478 14.5.5 Toxicity Assessment 479 References 479 15 Transport in the Environment and Ecotoxicity of Carbon Nanomaterials 487 Yingying Xu and Chunying Chen 15.1 Introduction 487 15.2 Transport of Carbon Nanomaterials in the Environment 488 15.2.1 Entry of Carbon Nanomaterials into the Environment 488 15.2.2 Fate and Transformation in the Environment 488 15.2.2.1 Oxidation 488 15.2.2.2 Photochemical Transformation 490 15.2.2.3 Dissolution and Precipitation 491 15.2.2.4 Adsorption 492 15.2.2.5 Biodegradation 493 15.3 Ecotoxicity of Fullerene 494 15.3.1 Effect of Fullerene on Microorganisms 494 15.3.2 Effect of Fullerene on Animals 495 15.3.2.1 Effect of Fullerene on Invertebrates 495 15.3.2.2 Effect of Fullerene on Vertebrates 496 15.3.3 Effect of Fullerene on Plants 496 15.3.3.1 Effect of Fullerene on Algae 496 15.3.3.2 Effect of Fullerene on Higher Plants 497 15.4 Ecotoxicity of Carbon Nanotubes (CNTs) 498 15.4.1 Effect of CNTs on Microorganisms 498 15.4.2 Effect of CNTs on Animals 499 15.4.2.1 Effect of CNTs on Invertebrates 499 15.4.2.2 Effect of CNTs on Vertebrates 501 15.4.3 Effect of CNTs on Plants 502 15.4.3.1 Effect of CNTs on Algae 502 15.4.3.2 Effect of CNTs on Higher Plants 503 15.5 Ecotoxicity of Graphene 504 15.6 Conclusion and Perspectives 506 Acknowledgments 506 References 506 16 Exposure Scenarios in the Workplace and Risk Assessment of Carbon Nanomaterials 515 Rui Chen and Chunying Chen 16.1 Introduction 515 16.1.1 Background 515 16.1.2 Exposure Routes and Exposure Scenarios 515 16.1.3 Exposure Metrics 516 16.1.4 Occupation Exposure Limit for Carbon Nanomaterials 516 16.1.5 Strategy for Exposure Assessment of Carbon Nanomaterials 517 16.2 Potential Exposure in theWorkplace 519 16.2.1 Carbon Nanotubes 519 16.2.2 Fullerenes, Metallofullerenes, and Graphenes 525 16.3 Exposure Risk Assessment and Engineering Control 527 16.3.1 Risk Assessment Strategy on Carbon Nanomaterials 527 16.3.2 Inhalation Exposure Assessment Method 529 16.3.3 Exposure Controls 530 16.4 Summary and Outlook 531 Acknowledgments 531 References 531 Index 535

Product Details

  • ISBN13: 9783527338719
  • Format: Hardback
  • Number Of Pages: 543
  • ID: 9783527338719
  • weight: 1328
  • ISBN10: 3527338713

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