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1 Introduction 1Sreekanth Thota and Debbie C. Crans 1.1 History of Metal Complexes 1 1.1.1 Introduction 1 1.1.2 Metal Complexes 1 1.1.3 Metal Complexes in Medicine 2 1.2 Nanotechnology 2 1.2.1 Introduction 2 1.2.2 Development of Nanotechnology 2 1.2.3 Nanotechnology in Medicine 3 1.3 Nanoparticles 4 1.3.1 Introduction 4 1.3.2 Development of Nanoparticles 5 1.3.2.1 Liposome-Based Nanoparticles 5 1.3.2.2 Polymeric Nanoparticles 5 1.3.2.3 Metal Nanoparticles 5 1.3.3 Nanoparticles in Science and Medicine 6 1.4 Nanotechnology-Supported Metal Nanoparticles 7 Acknowledgment 7 References 7 2 Methods for Preparation of Metal Nanoparticles 15Siavash Iravani 2.1 Introduction 15 2.2 Methods for Preparation ofMetallic NPs 15 2.2.1 Physical and Chemical Methods 15 2.2.2 Green and Bio-based Strategies 19 2.3 Conclusion 24 References 24 3 Metal Nanoparticles as Therapeutic Agents: A Paradigm Shift in Medicine 33Mahendra Rai, Dipali Nagaonkar, and Avinash P. Ingle 3.1 Introduction 33 3.2 Metal Nanoparticles in Diagnostics 35 3.2.1 Nanoparticles as Biolabels 35 3.2.2 Nanoparticulate Detection of Proteins 35 3.2.3 Nanobiosensing 36 3.2.4 In vivo Imaging 37 3.3 Advanced Drug Delivery 38 3.4 Nanoparticle-Mediated Gene Transfer 39 3.5 Nanotechnology in RegenerativeTherapies 41 3.5.1 Tissue Engineering and Implants 41 3.5.2 Bone Regeneration Materials 41 3.5.3 In Dentistry 42 3.5.4 CellTherapy 43 3.6 Nanoparticles–Essential Oils Combination Against Human Pathogens 43 3.7 Conclusion 44 Acknowledgment 44 References 44 4 Nanoparticles for Imaging 49Yerra Rajeshwar 4.1 Introduction 49 4.2 Nanoparticles 49 4.3 Nanoparticles as Diagnostic Probes 52 4.3.1 Nanoparticles as Blood Pool Contrast Agents 52 4.3.2 Imaging for MPS 54 4.3.3 Cell Labeling and Tracking 57 4.3.4 Labeling Implants, Transplants, and Grafts 60 4.3.5 Nano- and Microparticles for Molecular Imaging 62 4.4 Nanoparticle-BasedTheranostics 67 4.4.1 Nanoparticles for Imaging-Guided Interventions 67 4.4.2 Nano- or Microparticles for Imaging-Guided Hyperthermia Treatment 67 4.4.3 Imaging-Guided Drug Delivery 69 4.5 Conclusion 70 References 71 5 Soft-Oxometalates: A New State of Oxometalates and Their Potential Applications as Nanomotors 83Apabrita Mallick and Soumyajit Roy 5.1 Introduction to Soft-Oxometalates (SOMs) 83 5.1.1 Classification of Soft-Oxometalates 84 5.1.1.1 Spontaneously Formed Soft-Oxometalates 84 5.1.1.2 Designed Soft-Oxometalates 84 5.2 Application of Soft-Oxometalates 85 5.2.1 Control of Morphology of SOMs 85 5.2.2 SOMs in Catalysis 86 5.2.3 SOMs in Patterning 86 5.3 Active Nano/micro Motors 89 5.3.1 CatalyticMotors 89 5.3.2 Magnetically Propelled Motors 89 5.3.3 Electrically Propelled Motors 90 5.3.4 Light Driven Motors 90 5.3.5 Ultrasonically Driven Motors 90 5.4 Micro-Optomechanical Movement (MOM) in Soft-Oxometalates 90 5.5 Autonomous Movements Induced in Heptamolybdate SOMs 92 5.6 SOMs asWater Oxidation Catalysts 94 5.7 Conclusion 95 Acknowledgment 95 References 95 6 Medicinal Applications of Metal Nanoparticles 101Ayan K. Barui, Rajesh Kotcherlakota, and Chitta R. Patra 6.1 Overview 101 6.2 Introduction and Background 101 6.2.1 History of Medicinal Use of Metals,Metal Ions, and Complexes 103 6.2.2 Nanotechnology and Nanomedicine 104 6.2.3 Application of Disease-Specific Nanomedicine 105 6.2.4 Importance of Metal Nanoparticles in Biology 105 6.3 Biomedical Applications of Metal Nanoparticles 106 6.3.1 Delivery of Biomolecules Using Metal Nanoparticles 107 6.3.1.1 Drug Delivery 107 6.3.1.2 Nucleic Acid Delivery 112 6.3.1.3 Immunological Molecule Delivery 113 6.3.2 Anticancer Activities of Metal Nanoparticles 114 6.3.3 AntiangiogenicTherapy Using Metal Nanoparticles 116 6.3.4 Proangiogenic Properties of Metal Nanoparticles 117 6.3.5 Metal Nanoparticles in Bioimaging 119 6.3.6 Biosensing Applications of Metal Nanoparticles 120 6.3.7 Antimicrobial Activity of Metal Nanoparticles 122 6.3.8 Metal Nanoparticles in Neurodegenerative Diseases 124 6.3.9 Metal Nanoparticles in Tissue Engineering 126 6.3.10 Metal Nanoparticles in Diabetes 126 6.3.11 Metal Nanoparticles for Retinal Disorder 127 6.3.12 Anti-Inflammatory Effects of Metal Nanoparticles 127 6.3.13 Biologically Synthesized Nanoparticles for Biomedical Applications 128 6.4 Pharmacokinetics of Metal Nanoparticles 129 6.5 Status of Metal Nanoparticles in Clinical Study 131 6.6 Future Prospect of Metal Nanoparticles in Medicine 132 Acknowledgment 133 Abbreviations 133 References 135 7 Metal Nanoparticles in Nanomedicine: Advantages and Scope 155Tapan K. Sau, Arunangshu Biswas, and Parijat Ray 7.1 Introduction 155 7.1.1 Therapeutic Use of Metals: Historical Perspective 155 7.1.2 Nanomedicines and Metals 156 7.2 Advantages Associated with Metal Nanosystems 157 7.2.1 Metals as Nanosystems 158 7.2.1.1 Small Size and Large Surface Area-to-Volume Ratio 158 7.2.1.2 Shape and Morphology Dependence 159 7.2.2 Varieties of Metal Nanoparticles, Synthesis, and Fabrication Techniques 159 7.2.3 Inertness, Biocompatibility, and Ease of Surface Modifications 160 7.2.4 Optical Properties: Localized Surface Plasmon Resonance (LSPR) 162 7.2.5 Large Scattering and Absorption Cross Sections and Photothermal Effects 166 7.2.6 Enhanced Local Electromagnetic Field: Surface-Enhanced Spectroscopies 167 7.3 Applications and Scope 169 7.3.1 Targeted Drug Delivery and Controlled Release 169 7.3.2 Photothermal and Photodynamic Therapies and Cancer Treatment 173 7.3.3 Antimicrobial andWound Healing Effects 175 7.3.4 Clinical Diagnostics 177 7.3.4.1 Medical Imaging 178 7.4 Concluding Remarks 185 Acknowledgments 185 References 185 8 Applications of Metal Nanoparticles in Medicine/Metal Nanoparticles as Anticancer Agents 203Wenjie Mei and QiongWu 8.1 Advantages of Metal Nanoparticles 203 8.1.1 Stability and Homogeneity 203 8.1.2 Luminescence Property 204 8.1.3 Biocompatibility 204 8.1.4 Metabolic Pathways 204 8.2 Metal Nanoparticles as Anticancer Agents 205 8.3 Gold Nanoparticles 205 8.3.1 AuNPs as Therapeutic Agents 206 8.3.1.1 AuNPs in Plasmonic PhotothermalTherapy 206 8.3.1.2 AuNPs in Photodynamic Therapy 207 8.3.1.3 AuNPs as aTherapeutic Agent 207 8.3.2 AuNPs as Drug Carriers 208 8.3.2.1 Targeted Delivery of Anticancer Drugs 208 8.3.2.2 Delivery of Genes 209 8.3.3 AuNPs in Cancer Imaging 209 8.4 Silver Nanoparticles (AgNPs) 210 8.4.1 Synthesis of AgNPs 210 8.4.1.1 Chemical Methods 210 8.4.1.2 Physical Methods 210 8.4.1.3 Biological Methods 210 8.4.2 AgNPs as Inhibitor in Chemotherapy 211 8.4.2.1 AgNPs as Promising Inhibitor Against Tumor 211 8.4.3 AgNPs as Drug Carrier 212 8.4.4 AgNPs in Cellular Imaging and Clinic Diagnostics 213 8.4.5 Cytotoxicity of AgNPs 213 8.5 Copper Nanoparticles 214 8.5.1 Synthesis of CuNPs 214 8.5.2 Antibacterial Activity 214 8.5.3 Anticancer Activity 214 8.5.4 Molecular Imaging 215 8.5.5 Drug Carrier 216 8.6 Conclusion 217 Acknowledgments 217 References 217 9 Noble Metal Nanoparticles and Their Antimicrobial Properties 225Lini Huo and Peiyuan Li 9.1 Introduction 225 9.2 Synthesis of Antibacterial Noble Metal Nanoparticles 225 9.2.1 Physical Methods 225 9.2.2 Chemical Methods 226 9.2.3 Green Synthesis Methods 227 9.3 Antibacterial Nanomaterials and Their AntibacterialMechanism 227 9.3.1 Mechanisms of Nanoparticles Antibacterial Activity 228 9.4 Concluding Remarks and Future Outlook 229 References 230 10 Metal Nanoparticles and Their Toxicity 237Ivan Pacheco and Cristina Buzea 10.1 Introduction to Metal Nanoparticles Toxicity 237 10.2 Metal Nanoparticle Internalization and Biodistribution 238 10.3 Physicochemical Properties of Metal Nanoparticles 240 10.4 Nanoparticle Size and Toxicity 241 10.4.1 Size and Uniformity of Metal Nanoparticles 241 10.4.2 Nanoparticle Size-Dependent Toxicity 241 10.5 Nanoparticle Composition and Toxicity 244 10.5.1 Nanoparticles Composition 244 10.5.2 Comparative Toxicity of Metal Nanoparticles 246 10.5.3 Toxicity of Silver Nanoparticles 249 10.5.4 Toxicity of Metal Oxides 249 10.5.4.1 Titanium Dioxide Nanoparticles Toxicity 249 10.5.4.2 Zinc Oxide Nanoparticles Toxicity 250 10.5.4.3 Copper Oxide Nanoparticle Toxicity 250 10.5.4.4 Cerium Oxide Nanoparticles Toxicity 250 10.6 Nanoparticle Morphology and Toxicity 251 10.6.1 Nanoparticles Morphology 251 10.6.2 Nanoparticle Morphology-Dependent Toxicity 252 10.7 Nanoparticle Crystalline Structure and Toxicity 254 10.7.1 Nanoparticle Crystalline Structure 254 10.7.2 Crystalline Structure-Dependent Toxicity 255 10.8 Nanoparticle Surface and Toxicity 255 10.8.1 Hydrophobicity and Hydrophilicity 255 10.8.2 Catalytic Activity 256 10.8.3 Surface Functionalization-Dependent Toxicity 256 10.8.4 Surface Charge-Dependent Toxicity 257 10.9 Nanoparticle Magnetism and Toxicity 257 10.9.1 Magnetism of Nanoparticles Magnetic in Bulk Form 257 10.9.2 Magnetism of Nanoparticles Nonmagnetic in Bulk Form (Au, Pt, Pd) 261 10.9.3 Magnetic Nanoparticles Toxicity 261 10.9.3.1 Iron Oxide Nanoparticles Toxicity 262 10.9.3.2 Cobalt and Nickel Compounds Nanoparticles Toxicity 262 10.9.4 Gold and Platinum Nanoparticle Toxicity 263 10.9.4.1 Gold Nanoparticles Toxicity 263 10.9.4.2 Platinum Nanoparticle Toxicity 263 10.10 Interaction of NanoparticlesWithin Organisms 264 10.10.1 Formation of Protein Corona 264 10.10.2 Metal Nanoparticle Uptake by Cells 265 10.10.3 Nanoparticles Crossing the Placental Barrier 267 10.10.4 Nanoparticles Association to Cardiovascular Diseases 267 10.10.5 Central Nervous System Interaction with Nanoparticles 270 10.10.6 Immune System Interaction with Nanoparticles 270 10.10.7 Liver, Kidneys, and Other Organ Interaction with Nanoparticles 271 10.11 Other Novel Properties of Metal Nanoparticles 272 10.11.1 Optical Properties 272 10.11.2 Melting Temperature 274 10.12 Conclusions 276 References 276 Index 295

Sreekanth Thota is a Visiting Researcher at the Center for Technological Development in Health, Fundac?o Oswaldo Cruz - Fiocruz in Rio de Janeiro, Brazil. He studied Pharmaceutical Chemistry at Kakatiya University (India) and Rajiv Gandhi University of Health Sciences (Bangalore, India) and obtained his Ph.D from Jawaharlal Nehru Technological University Hyderabad (India) in 2011. He then did postdoctoral work at Colorado State University, USA. He received the 2013 CAPES-Fiocruz, Visiting Researcher award and has published over 40 articles in peer-reviewed journals. His research interest is focused on the drug discovery, medicinal chemistry, fundamental chemistry and biochemistry of ruthenium and other transition metal ions leading to applications in medicine. Debbie C. Crans is Professor of Organic and Inorganic Chemistry and in the Cell and Molecular Biology Program at Colorado State University, Fort Collins, USA. She obtained her Ph.D. in Chemistry from Harvard University with George M. Whitesides, USA, in 1985. She did a postdoctoral fellowship with Orville L. Chapman and Paul D. Boyer at UCLA in 1986. Her research interests lie in biological chemistry with expertise in metals in medicine and coordination chemistry with a focus on transition metals such as vanadium and platinum and interests in membrane model systems and hydrophobic compounds and lipids such as menaquinone. She received the Vanadis Award in 2004 and in the 2015 Cope Scholar Award. She has published over 190 articles in peer-reviewed journals.