Cellular and Molecular Toxicology of Nanoparticles (eBook)

Dr. Quaiser Saquib is currently working as an Assistant Professor in Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia. He is also serving as coordinator of Al-Jeraisy Chair for DNA Research in KSU. He earned his PhD from AMU, India. Much of his experience has been doing the molecular toxicity and biophysical research. Dr. Saquib has been conferred “Scientist of the Year Award-2016” by National Environmental Science Academy, India and “Young Scientist Award 2008” by Environmental Mutagen Society of India. There are 46 research publications, 2 books and 2 book chapters has been added to his credentials. He is principal and co-investigator in several projects funded by National Plan for Science and Technology, Saudi Arabia. Dr. Saquib is also engaged in teaching and training of graduate and postgraduate students at KSU. Dr. Mohammad Faisal is an Assistant Professor in the Department of Botany & Microbiology, King Saud University, Riyadh, Saudi Arabia. He received his PhD degree in Botany from the AMU, India. He is a well-known plant biotechnologist and an active researcher also worked as Postdoctoral Fellow at the Centro de Investigaciones Biologicas, Madrid, Spain and Young Scientist at AMU, Aligarh, India. He availed several national fellowships during his doctoral work. Dr. Faisal has been awarded Plant Biotechnologist Award-2017 by the SESR, India and Scientist of the Year Award-2015 by the NESA. He has published over 64 research articles and these papers have been cited over 1362 times with Google h index of 23. He holds life membership of several academic societies and fellow of the SESR. He is in the editorial board of the several peer-reviewed international journals. Professor Abdulaziz A. Al-Khedhairy is currently serving as Director of Twasol Research Excellence Program in King Saud University, Riyadh, Saudi Arabia. He has been appointed at several key academic and administrative positions in KSU, including Dean of Community College, Assistant Vice-President for Graduate Studies and Research. Prof. Al-Khedhairy is also supervising Al-Jeraisy Chair for DNA Research. His research interest includes molecular genetics of inherited diseases in the Saudi community and interactions of eukaryotic DNA with genotoxic chemicals and their prolonged effect on human genes. He has published 160 research articles, 9 book chapters and 2 books. He also has one USA patient. He has been conferred with KACST Golden Award for Excellence in Research. As a PI and CO-I, he has successfully supervised several projects funded by KACST, KSA. Dr. Abdulrahman Alatar is an Associate Professor at the Department of Botany & Microbiology, King Saud University, Riyadh, Saudi Arabia. He received his PhD degree in Plant Ecology in the year 2008 from KSU. He has been the Principal and Co-Investigator of the various projects funded by the different agencies and supervised 3 PhD students and 7 MSc students. He holds membership of several academic societies and participated in several national and international conferences. He published more than 65 scientific articles in different international journals published by the Elsevier, Springer, Wiley, Taylor and Francis etc. His work has been cited in various leading journals. He is the recipient of several awards and honors and have various academic and administrative contributions in the KSU. Currently, he is also serving as the Vice Dean of Graduate Studies, KSU, Riyadh, Saudi Arabia.

Preface 6
Acknowledgments 8
Contents 9
Contributors 11
About the Editors 15
1: Toxicity Assessment in the Nanoparticle Era 17
1.1 Introduction 17
1.2 In Vitro and in Vivo Studies 20
1.3 Physico-chemical Properties of Nanostructures 21
1.3.1 Size 21
1.3.2 Shape 21
1.3.3 Charge 22
1.3.4 Surface Modification 22
1.3.5 Crystalline Structure 23
1.3.6 Effects of Media 23
1.4 Route of Entry of Nanoparticles 23
1.4.1 Inhalation 23
1.4.2 Ingestion 24
1.4.3 Skin Penetration 24
1.5 Biodistribution 24
1.6 Nanoparticles Cellular Uptake 25
1.7 Common Toxicity Tests In vitro 27
1.7.1 MTT Assay 27
1.7.2 Lactate Dehydrogenase (LDH) Leakage Assay 27
1.7.3 2?,7?-Dichlorofluorescein Diacetate (DCF-DA) Assay 28
1.7.4 COMET Assay 28
1.8 Current State of Nano Risk Assessment 28
1.9 In Silico Toxicology 29
1.10 Conclusions 30
References 30
2: Mechanisms of Uptake and Translocation of Nanomaterials in the Lung 36
2.1 Introduction 36
2.2 The Respiratory Tract: Target Organ of Inhaled Nanomaterials 37
2.2.1 Structure of The Respiratory Tract 37
2.2.2 Particle Deposition 38
2.2.3 Clearance Mechanisms 39
2.3 Nanomaterial Internalisation 39
2.3.1 Mechanism of Internalization 39
2.3.2 Endocytic Pathways Used by Nanomaterials 40
2.3.3 Physico-chemical Characteristics Influencing NM Uptake 41
2.4 Nanomaterial Translocation 43
2.4.1 In Vitro Studies 43
2.4.2 In Vivo Studies 46
References 49
3: Transmucosal Nanoparticles: Toxicological Overview 52
3.1 Introduction 54
3.1.1 Overview of Mucosal System 54
3.1.1.1 Mucous and Pharmacology 54
3.1.2 Brief Discussion on Mucosal Routes of Exposure 55
3.1.2.1 Ocular Mucosa 55
3.1.2.2 Nasal Mucosa 55
3.1.2.3 Oral Mucosa 55
3.1.2.4 Pulmonary Mucosa 56
3.1.2.5 Rectal and Vaginal Mucosa 56
3.2 Fate of Nanoparticles via Transmucosal Route 56
3.2.1 Molecular and Cellular Interactions 57
3.2.1.1 Pathways of Internalisation 57
3.2.1.2 Protein Binding to NPs 58
3.2.1.3 Degradation 58
3.3 Mechanism of Toxicity at Cellular and Molecular Level 59
3.3.1 Physiochemical Properties of Nanoparticle and Their Toxic Effects 59
3.3.2 Mechanism of Toxicity of NPs 60
3.4 Toxicological Aspects of Nanoparticles via Different Transmucosal Routes 63
3.4.1 Ocular Mucosa- 63
3.4.2 Nasal Mucosa- 64
3.4.3 Oral Buccal Mucosa 65
3.4.4 Pulmonary Mucosa- 65
3.4.5 Rectal/Vaginal Mucosa- 66
3.5 Summary and Future Prospects 67
References 69
4: The Toxicity of Nanoparticles to Human Endothelial Cells 73
4.1 Introduction 73
4.2 Toxicity of NPs to Human Endothelial Cells 75
4.2.1 Cytotoxicity 75
4.2.2 Genotoxicity 76
4.2.3 Endothelial Activation 77
4.2.4 Dysfunction of NOS and Impaired NO Signaling 78
4.3 Mechanisms 78
4.3.1 Oxidative Stress 78
4.3.2 Inflammation 79
4.3.3 Dysfunction of Autophagy 79
4.4 Conclusions 80
References 81
5: The Role of Autophagy in Nanoparticles-Induced Toxicity and Its Related Cellular and Molecular Mechanisms 84
5.1 Introduction 85
5.2 Classification of Autophagy 85
5.3 The Role of Autophagy in Nanoparticles-Induced Toxicity 86
5.4 Physicochemical Mechanisms of Autophagy in Nanoparticles-Induced Toxicity 87
5.4.1 Dispersity 87
5.4.2 Size 87
5.4.3 Charge 88
5.4.4 Surface Chemistry 88
5.5 Cellular Mechanisms of Autophagy in Nanoparticles-Induced Toxicity 89
5.5.1 Lysosome Impairment 89
5.5.2 Mitochondria Dysfunction and Mitophagy 90
5.5.3 Endoplasmic Reticulum Stress and Endoplasmic Reticulum Autophagy 90
5.6 Molecular Mechanisms of Autophagy in Nanoparticles-Induced Toxicity 91
5.6.1 PI3K/Akt/mTOR Signaling Pathway 91
5.6.2 MAPK/ERK Signaling Pathway 92
5.6.3 Toll-Like Receptor Signaling Pathways 92
5.6.4 Hypoxia-Inducible Factor-1? 92
5.6.5 Oxidative Stress 93
5.7 Conclusion 95
References 95
6: Nanoparticles-Caused Oxidative Imbalance 98
6.1 Redox Status - Background 99
6.2 Redox Balance as Guarantee of Properly Functioning Signal Transmission 99
6.3 Reactive Oxygen Species Generated in Response to Nanoparticles 101
6.4 ROS Generation in Course of Action of Nanoparticles Is Strongly Dependent on Particle Size 102
6.5 Reactive Oxygen Species Generated by Nanoparticles: Influence of Both on Signal Transduction Pathways 104
6.6 Summary 106
References 107
7: Toxicity of Metal Oxide Nanoparticles 112
7.1 Introduction 112
7.1.1 Metal Oxide Nanoparticles 113
7.1.2 Zinc Oxide (ZnO) Nanoparticles 114
7.1.2.1 Photocatalysis of ZnO 115
7.1.2.2 Toxicity of ZnO Nanoparticles 115
7.1.3 Titanium Dioxide (TiO2) Nanoparticle Toxicity 116
7.1.4 Iron Oxide Nanoparticle Toxicity 119
7.1.5 Copper Oxide Nanoparticle (CuO and Cu2O) Toxicity 123
7.1.6 Cerium Oxide Nanoparticle Toxicity 124
7.1.7 Mechanisms of Metal Oxide Nanoparticle Toxicity 126
7.2 Conclusion 129
References 129
8: Relevance of Physicochemical Characterization of Nanomaterials for Understanding Nano-cellular Interactions 136
8.1 Introduction 137
8.2 The Physicochemical Characterization of Nanomaterials 138
8.3 Closely Related NMs Reveal Distinct Genotoxic Effects 139
8.4 The Influence of Cell Environment in the Biological Effects of NMs 144
8.5 Shifting from In Vitro Toxicology Assays to In Vivo Evidence 148
8.6 New Avenues for Understanding Nano-­cellular Interactions 151
8.7 Final Remarks 152
References 152
9: Toxicogenomics: A New Paradigm for Nanotoxicity Evaluation 156
9.1 Introduction 157
9.2 Toxicogenomics in Nanoparticles Research 157
9.3 Nanoparticles Toxicity Analysis by RNA-seq 158
9.4 Microarray Analysis of Nanoparticles Toxicity 161
9.5 Toxicological Potential of Nanoparticles 168
9.6 Conclusion and Future Perspective 170
References 171
10: Nickel Oxide Nanoparticles Induced Transcriptomic Alterations in HEPG2 Cells 175
10.1 Introduction 176
10.2 Materials and Methods 177
10.2.1 NiO-NPs Characterization 177
10.2.2 Cell Culture and NiO-NPs Exposure 177
10.2.3 In Vitro DNA Damage Analysis by Comet Assay 178
10.2.4 ROS Measurements in HepG2 Cells 178
10.2.5 RT2 Profiler PCR Array Analysis 178
10.3 Results 179
10.3.1 NiO-NPs Characterization 179
10.3.2 DNA Damage in HepG2 Cells 179
10.3.3 Quantitative and Qualitative Analysis of Intracellular ROS 179
10.3.4 qPCR Array of HepG2 Cells 180
10.4 Discussion 181
10.5 Conclusion 184
References 184
11: Nanoparticle-Protein Interaction: The Significance and Role of Protein Corona 187
11.1 Introduction 187
11.2 Formation of Protein Corona 188
11.3 Composition of Protein Corona 191
11.4 Factors Influencing Protein Corona 193
11.4.1 Nanoparticle Size 193
11.4.2 Nanoparticle Surface Properties 193
11.4.3 Time of Exposure 194
11.4.4 Temperature 196
11.4.5 Biological Environment 197
11.4.6 Plasma Concentration 198
11.5 Consequences of Protein Corona 200
11.5.1 Effect on Nanoparticle Size 200
11.5.2 Effect on Zeta-Potential 200
11.5.3 Cellular Targeting of Nanoparticles 200
11.5.4 Cellular Uptake of Nanoparticles 202
11.5.5 Effect on Drug Release 204
11.5.6 Nanoparticle Biocompatibility and Toxicity 204
11.6 Attempts on the Fabrication of Corona Free Nanoparticles 205
11.7 Conclusion 207
References 207
12: Cellular and Molecular Toxicity of Iron Oxide Nanoparticles 211
12.1 Introduction 212
12.1.1 Biomedical Applications 212
12.1.2 Structure and Composition of Iron Oxide Nanoparticles 213
12.2 Cellular and Molecular Effects 213
12.2.1 Viability 214
12.2.2 Oxidative Damage 215
12.2.3 Mitochondrial Alterations 215
12.2.4 Cell Membrane Disruptions 216
12.2.5 Genomic Alterations 217
12.2.6 Other Cellular Effects 218
12.3 Toxicity Mechanism 220
12.4 Conclusions 220
References 221
13: Detection of DNA Damage Induced by Cerium Dioxide Nanoparticles: From Models to Molecular Mechanism Activated 226
13.1 Introduction 227
13.2 Physical-Chemical Characteristics of Nanoceria Governing Biological Outcomes 229
13.3 DNA Damage Response Pathways Integrated to Cellular Outcomes Detected by In Vitro Systems 230
13.4 Nanogenotoxicity Detected by In Vivo Systems 232
13.5 General Aspects in the Cyto-­Genotoxic Study of Nanoceria 233
13.6 Conclusion 233
References 235
14: Mechanisms Underlying Neurotoxicity of Silver Nanoparticles 238
14.1 Commercial and Medical Applications of AgNPs 239
14.2 Factors Influencing Toxicity of AgNPs 241
14.2.1 Size and Shape 241
14.2.2 Coating of the Surface 242
14.2.3 Liberation of Ag Ions 242
14.2.4 Protein Corona 243
14.3 Cellular Targets for AgNPs in the Central Nervous System 244
14.3.1 The Blood-Brain Barrier 245
14.3.2 Neurons and Synapses 247
14.3.3 Myelin 248
14.3.4 Glial Cells 249
14.4 Molecular Mechanisms of Neurotoxicity Exerted by AgNPs 250
14.4.1 Interactions with Receptors and Channels 250
14.4.2 Mitochondrial Damage 251
14.4.3 Oxidative Stress 251
14.4.4 Inflammation 253
14.4.5 Cell Death 253
14.4.5.1 Apoptosis 253
14.4.5.2 Autophagy 254
14.5 Summary 255
References 256
15: Toxic and Beneficial Potential of Silver Nanoparticles: The Two Sides of the Same Coin 262
15.1 Introduction 263
15.2 AgNP Toxicity in Aquatic Environments 263
15.3 AgNP Interaction with Natural Organic Matter (NOM) 265
15.4 AgNPs and the Trojan Horse Mechanism 266
15.5 AgNPs as Nanocarriers (NC) 267
15.6 AgNP Cytotoxicity: Apoptosis, Necrosis and Autophagy 268
15.7 Conclusion 270
References 270
16: Molecular and Cellular Toxicology of Nanomaterials with Related to Aquatic Organisms 274
16.1 Introduction 275
16.2 Types of Nanomaterials 276
16.3 Nanotechnology in Aquaculture and Fisheries 276
16.4 Toxicological Profiling of Different Types of NPs 276
16.5 Toxicity Mechanisms of Nanoparticles 277
16.6 Silver Nanoparticles (AgNPs) and Aquatic Organism Toxicity 277
16.7 Gold Nanoparticles (AuNPs) and Aquatic Organism Toxicity 282
16.8 Quantum Dots (QDS) and Aquatic Organism Toxicity 284
16.9 Other Metallic Nanoparticles (Iron, Copper and Zinc Oxides) and Aquatic Organism 285
16.10 Polymeric Nanoparticles (Chitosan, Poly (Lactic-co-­glycolic Acid) Alginate) 286
16.11 Genotoxicity of Aquatic Animals with References to Different Nanoparticles 287
16.12 Molecular Response of Stress-Related Gene with Respect to Different Nanoparticles 288
16.13 Conclusion and Future Direction 289
References 290
17: Cytotoxicity and Physiological Effects of Silver Nanoparticles on Marine Invertebrates 296
17.1 Scientific Context 297
17.1.1 Fate of Silver in Estuarine Waters 297
17.1.2 Occurrence of AgNPs in Natural Waters 298
17.2 Toxicity Effects of AgNPs on Marine Invertebrates After Short and Chronic Exposures 298
17.2.1 Basic Mechanisms 298
17.2.2 Overview of Toxicity Studies 299
17.2.3 Bivalves 299
17.2.4 Annelids 306
17.2.5 Benthic and Pelagic Invertebrates 306
17.3 Physicochemical Interactions of AgNPs with Membranes and Biomolecules 308
17.3.1 Physical and Chemical Processes 308
17.3.2 Interactions with Cells and Tissues 309
17.3.3 Effects of Interactions with Biomolecules 310
17.4 Cellular Toxicity Mechanisms of Polymer-Coated AgNPs During Sea Urchin Developmental Stages 311
17.4.1 Embryotoxicity of AgNPs 311
17.4.2 Toxicity of AgNPs After Metamorphosis 314
17.4.3 Comparative Toxicity of Dissolved and Particulate Silver 315
17.4.4 Starvation Effects on AgNP Toxicity 316
17.5 Remaining Questions and Conclusion 316
References 317
18: A Drosophila Model to Decipher the Toxicity of Nanoparticles Taken Through Oral Routes 321
18.1 Introduction 322
18.2 Nanoparticles Cross Through Oral Route: Food, Medicine, Mouth Implants 322
18.3 Advantage of Drosophila over Other Models 323
18.3.1 Mode of Transportation of Nanoparticle Through Human and Drosophila Gut 323
18.4 Assessment of NP Toxicity Using Biochemical Methods 325
18.5 Toxicity at Phenotypic Level 326
18.6 Signaling Pathways Affected Due to NPs 328
18.7 NPs Affecting Survivorship and Fecundity of Drosophila 328
18.8 Conclusion 329
References 329
19: Using of Quantum Dots in Biology and Medicine 333
19.1 Introduction 333
19.2 Synthesis of QDs 334
19.3 The Prospects of QDs Modification for Biomedical Use 336
19.4 Uses of QDs in Biology and Medicine 337
References 342
Index 345