Prof. Ashutosh Tiwari is Managing Director, Tekidag AB and Group leader, Smart Materials and Biodevices at the Biosensors and Bioelectronics Centre, Linköping University, Sweden; Editor-in-Chief, Advanced Materials Letters; Secretary General, International Association of Advanced Materials; a materials chemist and also a docent in applied physics from Linköping University, Sweden. He has published more than 425 articles, patents, and conference proceedings in the field of materials science and technology and has edited/authored about 25 books on the advanced state-of-the-art of materials science and technology. He is a founding member of the Advanced Materials World Congress, Smart Materials and Surfaces, Korean Advanced Materials World Congress, African Advanced Materials World Congress, European Graphene Forum and the World Technology Forum.

Jeong-Woo Choi is a Professor at Department of Chemical & Biomolecular Engineering and a director of Institute of Integrated Biotechnology, Sogang University, South Korea. He received Ph. D. in Rutgers University (USA), D.Eng. in Tokyo Institute of Technology (Japan) and MBA in University of Durham (UK); a visiting scientist in IBM Almaden Research Center and Mitsubishi Electronics Advanced Technology R&D Center. He is an editorial member of Biochip Journal, Biotechnology & Bioprocess Engineering, and J. Ind. & Eng. Chem. He has published more than 340 articles in peer-reviewed international journals and 46 patents in biosensor and bioelectronics fields, and he has edited/authored fifteen books on biosensor and advanced biomaterials.

Preface xiii

Part 1: System Biology and Translational Medicine

1 Aberrant Signaling Pathways 3
Gulnaz T. Javan, Sheree J. Finley, Ismail Can, Amandeep Salhotra, Ashinm Malhotra, and Shivani Soni

1.1 Cancer 4

1.2 Pathways Deregulated in Cancer: Introduction 4

1.3 Introduction to Nanotechnology 6

1.3.1 Overview of Clinical Nanotechnology 9

1.3.2 Current Usage in Cancer Treatment 13

1.4 Current Uses in Cancer Diagnostic 14

1.4.1 The Phosphatidylinositol 3-Kinase-AKT Pathway 15

1.4.2 The MAPK Pathway 18

1.4.3 mTOR Pathway 20

1.4.4 Receptor Tyrosine Kinase 23

Acknowledgment 26

References 27

2 Application of Nanoparticles in Cancer Treatment 37
Behnoud Hormozi

2.1 Introduction 38

2.1.1 Nanotechnology 38

2.1.2 Nanobiotechnology 38

2.1.3 Nanotechnology in Medicine 39

2.1.4 Cancer and Nano in Medicine 41

2.2 Nanoparticles in Cancer Treatment 41

2.3 Nanoparticle Platforms as Drug Delivery Systems for Cancer Therapy 43

2.3.1 Lipid-based Nanoparticle Platforms 44

2.3.2 Polymer-based Nanoparticle Platforms 45

2.3.3 Protein-based Nanoparticle Platforms 47

2.3.4 Inorganic Nanoparticle Platforms 47

2.4 Theranostic Nanomedicine 50

2.4.1 Theranostic Nanomedicine for Cancer Therapy 54

2.5 Selective Drug Delivery and Encapsulation for Chemotherapy 54

2.6 Stimuli-Sensitive Nanopreparations 55

2.7 Multifunctional Nanopreparations 56

2.8 Cancer Nanotechnology: Future and Challenges 58

References 59

3 Biomacromolecule-Gated Mesoporous Silica Drug Delivery Systems for Stimuli-Responsive Controlled Release 67
Xuezhong Du

3.1 Introduction 68

3.2 Protein-Gated MSN Drug Delivery Systems 69

3.2.1 Ligand-Binding Protein-Gated MSN Systems 70

3.2.2 Metal-Chelating Protein-Gated MSN Systems 74

3.3 DNA-Gated MSN Drug Delivery Systems 75

3.3.1 Single-Stranded DNA-Gated MSN Systems 76

3.3.2 Double-Stranded DNA-Gated MSN Systems 77

3.3.3 Hairpin or Quadruplex DNA-Gated MSN Systems 80

3.3.4 Native DNA-Gated MSN Systems 83

3.3.5 Near-Infrared Light-Triggered DNA-Gated MSN Systems 87

3.4 Conclusions and Perspectives 89

Acknowledgments 90

References 90

4 Construction of Functional DNA Nanostructures for Theranostic Applications 93
Jiang Li, Fan Li, Hao Pei, Lihua Wang, Qing Huang, and Chunhai Fan

4.1 The Progress of Structural DNA Nanotechnology 94

4.2 DNA Nanostructures for Diagnostics 96

4.3 DNA Nanostructures for Diagnostics on the Interface 96

4.4 Diagnostic in Homogeneous Solution 99

4.4.1 Spherical Nucleic Acids (SNA) Probes for Detections in Solution 99

4.4.2 Nanochips in Solution 100

4.4.3 Intracellular/In Vivo Diagnosis 103

4.5 DNA Nanostructures for Therapeutics 106

4.5.1 Delivery of Small-Molecular Drugs 107

4.5.2 Delivery of CpG DNAs 109

4.5.3 RNA Interference (RNAi) 111

4.5.4 Delivery of Proteins 114

4.6 Integration of Diagnosis and Therapy: Smart DNA Theranostic Nanodevices 115

4.7 Targeted Delivery 115

4.8 Controlled/Triggered Release 117

4.9 Summary and Perspectives 119

4.9.1 The Bioeffects of DNA Nanostructures 119

4.9.2 Purity and Yield 120

4.9.3 Dynamic Structures for Theranostic 120

References 121

Part 2: Imaging and Therapeutics

5 Dimercaptosuccinic Acid-Coated Magnetic Nanoparticles as a Localized Delivery System in Cancer Immunotherapy 133
Raquel Mejías, Lucía Gutiérrez, María P. Morales, and Domingo F. Barber

5.1 Introduction 134

5.1.1 Nanoparticle-based Drug Delivery Systems 134

5.1.2 Nanoparticles for Drug Delivery in Cancer Treatment 135

5.1.3 Magnetic Nanoparticles (MNP) 135

5.1.4 Nanoparticle Biodistribution and Degradation 136

5.2 Nanoparticle Detection and Quantification: In Vitro and In Vivo Techniques 137

5.2.1 Optical Microscopy 137

5.2.2 Colorimetric Assays 137

5.2.3 Transmission Electron Microscopy 138

5.2.4 Magnetic Methods 140

5.2.5 Elemental Analysis 142

5.2.6 Nuclear Magnetic Resonance (NMR) 143

5.3 Evaluation of Nanoparticle-Induced Toxicity 143

5.3.1 In Vitro Toxicity 143

5.4 Magnetic Targeting of Nanoparticles 147

5.5 A Specific Example: DMSA-Coated Magnetic Nanoparticles 148

5.5.1 In Vitro DMSA-MNP Uptake and Intracellular Localization 148

5.5.2 In Vitro DMSA-MNP Toxicity 149

5.5.3 In Vitro DMSA-MNP-Induced Cell Stress and Apoptosis 150

5.5.4 In Vivo DMSA-MNP Distribution 150

5.5.5 In Vivo DMSA-MNP-Induced Toxicity 152

5.5.6 In Vivo DMSA-MNP Biotransformation 152

5.6 Conclusions 153

Acknowledgments 154

References 154

6 Cardiovascular Nanomedicine 159
Suryyani Deb and Hirak Kumar Patra

6.1 Introduction 160

6.2 Nanoscale Cardiovascular Diagnostics 160

6.2.1 Cardiac Molecular Biomarker Detection from Peripheral Blood 161

6.2.2 Diagnosis through Nano-based Molecular Imaging 163

6.2.3 Determination of Stem Cell Delivery 165

6.3 Nanotechnology in Cardiovascular Therapeutics 167

6.3.1 Drug Delivery 167

6.3.2 Gene Delivery 169

6.3.3 Tissue Engineering 169

6.4 Nanotechnology in the Surgery of Cardiovascular Disease 170

6.5 Conclusion 172

References 173

7 Chitosan-based Interpenetrating Polymeric Network Systems for Sustained Drug Release 183
Amit Kumar Nayak and Dilipkumar Pal

7.1 Introduction 184

7.2 IPNs and Their Uses in Drug Delivery 185

7.3 Chitosan 187

7.4 Chitosan-Tamarind Seed Polysaccharide IPN Microparticles and Matrix Tablets for Sustained Release of Aceclofenac 189

7.5 Chitosan-Hydroxyethyl Cellulose IPN Microspheres of Isoniazid 193

7.6 Chitosan-Methyl Cellulose IPN Microspheres of Theophylline 194

7.7 Chitosan-Acrylamide-Grafted-Poly(Vinyl Alcohol) and Hydrolyzed Acrylamide-Grafted-Poly(Vinyl Alcohol) IPN Microgels of Cefadroxil 198

7.8 Chitosan-Poly(N-Isopropylacrylamide) IPN Discs of Diclofenac Sodium 199

7.9 Chitosan-Poly(Ethylene Oxide-Grafted-Acrylamide) Semi-IPN Hydrogel Microspheres of Capecitabine 200

7.10 Acrylamide-Grafted Dextran-Chitosan Semi-IPN Microspheres of Acyclovir 201

7.11 Chitosan-Acrylamide-Grafted Hydroxyethylcellulose Semi-IPN Microspheres of Diclofenac Sodium 202

7.12 Poly [N-Acryloylglycine-Chitosan] IPN Hydrogel of 5-Fluorouracil 202

7.13 Chitosan-N,N′-Dimethylacrylamide Semi-IPN Microspheres of Chlorothiazide 203

7.14 Conclusion 203

References 204

8 Nanocapsules in Biomedicine 209
Frank J. Hernandez, Murat Kavruk, Luiza I. Hernandez, and Veli C. Ozalp

8.1 Nanocapsules: A Novel Nano-Drug Delivery System 210

8.2 Magic Bullets: Nanocapsules in Future Medicine 211

8.3 In Vitro Applications of Nanocapsules 212

8.3.1 Functionalized Mesoporous Silica Materials for Controlled Drug Delivery 212

8.3.2 Cationic Polymer Nanocapsules for Controlled Multi-drug Delivery 220

8.3.3 Lipid Nanocapsules 221

8.4 In Vivo Applications of Nanocapsules 224

8.4.1 In Vivo Diagnostic Imaging 225

8.4.2 In Vivo Therapeutics 226

8.5 Conclusions 228

References 228

9 Chitosan-based Polyelectrolyte Complexes 235
Bojan Èalija, Nebojša Cekiæ, and Jela Miliæ

9.1 Introduction 236

9.2 Chitosans: Chemical Structure, Physicochemical Properties, and Toxicological and Regulatory Aspects 237

9.2.1 Chemical Structure and Source 237

9.2.2 Physicochemical Properties 238

9.2.3 Toxicological and Regulatory Aspects 239

9.3 Polyelectrolyte Complexes: Theoretical Background, Structure, and Basic Properties 240

9.4 Chitosan-based Polyelectrolyte Complexes in Particulate Drug Carriers 242

9.4.1 PECs Comprised of Chitosans and Natural or Semisynthetic Polyanions 243

9.4.2 PECs Comprised of Chitosans and Synthetic Polyanions 249

9.4.3 Influence of Chitosans Functional Properties and Experimental Conditions on Polyelectrolyte Complexation 254

9.5 Characterization of Chitosan-Based PECs and Chitosan-based PEC Particulate Drug Carriers 258

9.5.1 Size and Morphology 258

9.5.2 Zeta Potential 259

9.5.3 Structural Analysis 259

9.5.4 Encapsulation Efficiency and Drug Loading Capacity 261

9.5.5 In Vitro Swelling Studies 262

9.5.6 In Vitro Drug Release Studies 263

9.6 Conclusion 263

Acknowledgment 264

References 264

Part 3: Diagnostics and Featured Prognostics

10. Non-invasive Glucose Biosensors Based on Nanomaterials 273
Farnoush Faridbod, Mohammad Reza Ganjali, Bagher Larijani and Parviz Norouzi

10.1 Diabetes and Its Prevalence 274

10.2 Importance of Glucose Monitoring 274

10.3 Glucose Measurement Methods 275

10.4 Non-invasive Glucose Determination 275

10.4.1 Non-invasive Glucose Determination Using Tissues 276

10.4.2 Non-invasive Glucose Determination Method Using Fluids 277

10.5 Glucose Biosensors 279

10.6 New Generation of Non-invasive Glucose Biosensors-Based Nanomaterials 281

10.7 Future Perspective in Glucose Monitoring 290

10.8 Conclusion 292

References 292

11 Self-Directed Assembly of Nanoparticles 297
Arun Prakash Upadhyay, Dilip Kumar Behara, Gyan Prakash Sharma, Raj Ganesh S. Pala, and Sri Sivakumar

11.1 Introduction 297

11.2 Self-Assembly through Molecular Interactions/Forces 298

11.2.1 Van der Waals Interactions 298

11.2.2 Electrostatic Interaction 301

11.3 Hydrogen-Bonding Interactions 304

11.3.1 Covalent Interactions 306

11.3.2 DNA-Based Cross-Linking Interactions 311

11.4 Directed Self-Assembly by External Forces 315

11.4.1 Magnetic Field-Driven Directed Self-Assembly 315

11.4.2 Electric Field-Driven Directed Self-Assembly 319

11.4.3 Flow Field-Driven Directed Self-Assembly 321

11.5 Conclusion 325

Acknowledgment 326

References 326

Index 337

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