Advances in Nanotheranostics II (eBook)

Prof. Zhifei Dai obtained his Ph.D. in Physical Chemistry at the Institute of Photographic Chemistry, Chinese Academy of Sciences in 1998. From 1999 to 2005, he worked at the School of Sciences, Kwansei Gakuin University in Japan, Max-Planck Institute of Colloids and Interfaces in Germany, and the School of Medicine, Emory University in USA, respectively. In March 2005, he became a Professor at the School of Life Science and Technology, Harbin Institute of Technology, China. In May 2012, he moved to the Department of Biomedical Engineering, College of Engineering, Peking University, China. His research focuses on the multifunctional nanoparticles for drug delivery and contrast enhanced imaging. He is a member of editorial board for several international and national journals such as Bioconjugate Chemistry, Theranostics, Journal of Interdisciplinary Nanomedicine, IET Nanobiotechnology, BioMed International Research, Chinese Journal of Nuclear Medicine and Molecular Imaging and so on. He is now a standing committee member of China Association of Medical Ultrasound Equipment and Chinese Association of Ultrasound in Medicine and Engineering, an executive member of the council of Chinese Society for Functional Materials, and a committee member of the Acoustic Society of China. He received many honors and awards including National Natural Science Fund for Outstanding Young Researcher, New Century Talents of Chinese Ministry of Education, Longjiang Scholar Distinguished Professor, and the First Prize of the Natural Science Award of Heilongjiang Province.

Preface 6
Contents 8
Contributors 10
Part I: Magnetic Nanoparticles for MRI-Based Theranostics 13
Chapter 1: Design of Magnetic Nanoparticles for MRI-­Based Theranostics 14
1.1 Introduction 14
1.1.1 The Principle of MRI 15
1.1.2 The MRI Contrast Agents 16
1.2 Chemical Preparation of MNPs for MRI Contrast Agents 18
1.2.1 Coprecipitation Method 18
1.2.2 Polyol Process 18
1.2.3 Ultrasonic Chemical Method 19
1.2.4 Soft Template Synthesis Method 19
1.2.5 Thermal Decomposition Method 20
1.2.6 Solvothermal Method 22
1.3 Nano Contrast Agents for MRI 22
1.3.1 T1 Nano Contrast Agents 23
1.3.2 T2 Nano Contrast Agents 25
1.4 Multifunctionalization and Application of MNPs as MRI Contrast Agents 26
1.4.1 Multifunctionalization Methods 27
1.4.1.1 Ligand Exchange or Adsorption of Organic Molecules 27
1.4.1.2 Polymer Coating 29
1.4.1.3 Silica Coating 32
1.4.1.4 Liposome and Micelle Encapsulation 33
1.4.2 Theranostic Applications of MRI-Based MNPs 34
1.4.2.1 Magnetic Targeting Therapy 34
1.4.2.2 Magnetic Controlling Drug Delivery 35
1.4.2.3 Magnetic Hyperthermia 36
1.4.2.4 Cell Fate Controlling by Magnetic Field 37
1.5 Conclusions and Outlook 39
References 40
Chapter 2: Controlled Synthesis and Surface Modification of Magnetic Nanoparticles with High Performance for Cancer Theranostics Combining Targeted MR Imaging and Hyperthermia 49
2.1 Controlled Synthesis and Surface Modification of MNPs with High Performance 50
2.1.1 Conventional Synthesis of MNPs 50
2.1.2 Advantage of Synthesis of High-Quality MNPs by Thermal Decomposition 52
2.1.2.1 Formation Mechanism of Monodisperse MNPs by Thermal Decomposition 52
2.1.2.2 Size Effects 52
2.1.2.3 Shape Effects: From 0-D Nanocrystals to 3-D Nanoclusters 53
2.1.2.4 Magnetic Metal-Dopant Effects 58
2.1.2.5 Metal Alloy 60
2.1.3 Surface Modification of MNPs 61
2.1.3.1 Ligand Conjugation 61
2.1.3.2 Hydrophobic Interaction 63
2.1.3.3 Precious Metal and Inorganic Material Coating 65
2.2 MNPs with High Performance for MR Imaging Diagnostics 68
2.3 MNPs with High Performance for Cancer Targeted Hyperthermia 70
References 77
Chapter 3: Molecular Imaging of Tumor Angiogenesis with Magnetic Nanoprobes 84
3.1 Brief Introduction to Tumor Angiogenesis 85
3.2 Modalities Used for Tumor Angiogenesis Imaging 86
3.3 Principle of MRI 88
3.4 MRI Contrast Agents 91
3.5 MR Molecular Imaging of Tumor Angiogenesis by Targeting Integrin ?v?3 92
3.5.1 Imaging with Gd(III)-Containing Contrast Agents 92
3.5.2 Imaging with Superparamagnetic Iron Oxide (SPIO) Nanoparticles 98
3.5.3 Imaging with Dual-Targeting Probes 106
3.5.4 Biological Effects of RGD Peptide-Conjugated Probes on Tumor Cells 106
3.6 Summary and Future Perspectives 108
References 109
Part II: Ultrasonic Theranostic Agents 114
Chapter 4: Multifunctional Ultrasound Contrast Agents Integrating Targeted Imaging and Therapy 115
4.1 Introduction 115
4.2 General Design of Ultrasound Contrast Agents 117
4.2.1 Requirements of an Ideal Ultrasound Contrast Agent 117
4.2.2 General Design of the Microbubble-Based Ultrasound Contrast Agents 117
4.2.3 Ultrasound Contrast Agent Based Drug Delivery 119
4.2.4 Tissue-Specific Ultrasound Contrast Agents 119
4.2.5 The Effect of the Microbubble Size Distribution 121
4.3 Ultrasound Contrast Agent for Molecular Imaging 121
4.3.1 Basic Concept of Ultrasound Molecular Imaging 121
4.3.2 Ultrasound Molecular Imaging of Cancer 122
4.3.3 Ultrasound Molecular Imaging of Cardiovascular Disease 123
4.4 Ultrasound Contrast Agents for Multimodal Imaging 124
4.4.1 US/MR Dual-Modal Imaging Contrast Agents 124
4.4.2 US/Optical Dual-Modal Imaging Contrast Agents 126
4.4.3 US/Photoacoustic Dual-Modal Imaging Contrast Agents 127
4.4.4 Trimodal Imaging Contrast Agents 129
4.5 Multifunctional Ultrasound Contrast Agents for Imaging-Guided HIF Therapy 131
4.6 Ultrasound Contrast Agents Enhanced Imaging-Guided Photothermal Therapy 134
4.6.1 Hybrid Ultrasound Contrast Agents for Imaging-Guided Photothermal Therapy 134
4.6.2 Ultrasound Contrast Agents Based on Polypyrrole Microcapsules for Imaging-Guided Photothermal Therapy 141
4.7 Ultrasound Contrast Agents for Imaging-Guided Drug Delivery 145
4.8 Photoacoustic Effect-Based Tumor Therapy 150
4.9 Conclusion and Perspective 153
References 153
Chapter 5: Next-Generation Ultrasonic Theranostic Agents for Molecular Imaging and Therapy: Design, Preparation, and Biomedical Application 160
5.1 Introduction 160
5.2 Design and Preparation 161
5.2.1 The Development Process and Classification of UCA 161
5.2.2 Microbubble Production Techniques 162
5.2.2.1 Traditional Methods 162
5.2.2.2 Microfluidic Chip Methods 163
5.2.3 Preparation of Targeted Microbubbles 165
5.2.4 Drug-Loaded Microbubbles 166
5.2.5 Fluorocarbon-Based UCA 167
5.2.6 Multimodality UCA 168
5.2.6.1 US/PA 169
5.2.6.2 US/MRI 171
5.2.6.3 US/CT 172
5.2.6.4 Other Imaging 172
5.3 Biomedical Applications 174
5.3.1 Targeted UCA 174
5.3.1.1 Imaging Angiogenesis 174
5.3.1.2 Imaging Ischemia Disease 176
5.3.1.3 Diagnosis of Inflammatory Disease 176
5.3.1.4 Molecular Imaging of Intravascular Atherosclerosis and Thrombus 179
5.3.2 Theranostic Applications 182
5.3.2.1 General Introduction 182
5.3.2.2 Imaging, Drug and Gene Delivery, and Image-Guided Therapy 184
5.4 Summary and Outlook 187
5.4.1 Superiorities and Advantages 187
5.4.2 Challenges and Limitations 188
References 188
Chapter 6: Multifunctional Hollow Mesoporous Silica Nanoparticles for MR/US Imaging-Guided Tumor Therapy 196
6.1 Introduction 196
6.2 Design, Synthesis and Characterization of HMSNs 198
6.2.1 Synthetic Approach for HMSNs 198
6.2.2 Structural Difference-Based Selective Etching Strategy 200
6.2.3 Design and Fabrication of HMSN-Based Multifunctional Composite Nanocapsules 203
6.2.4 Developments of the Crucial Structural/Compositional Parameters of HMSNs 204
6.3 HMSNs as the Contrast Agents (CAs) for MR Imaging 204
6.3.1 HMSNs for T1-Weighted MR Imaging 204
6.3.2 HMSNs for T2-Weighted MR Imaging 206
6.4 HMSNs as the Contrast Agents (CAs) for Ultrasound Imaging 208
6.4.1 Imaging Mechanism of HMSN-Based UCAs 210
6.4.2 Phase-Change Material (PCM)-Encapsulated HMSN-­Based UCAs 213
6.4.3 Intelligent Design of HMSN-Based UCAs 215
6.5 HMSNs for HIFU Tumor Therapy 217
6.5.1 HMSN-Based Composite Nanocapsules for Imaging-­Guided HIFU Cancer Surgery 218
6.5.2 HMSN-Based Composite Nanocapsules for Combining Drug Delivery and HIFU Cancer Surgery 220
6.6 Conclusions and Outlook 223
References 224
Part III: Nanoparticles for Cancer Theranostics 230
Chapter 7: Multifunctional Nanoprobes for Multimodality Targeted Imaging and Therapy of Gastric Cancer 231
7.1 Introduction 231
7.2 Multifunctional Fluorescent Magnetic Nanoprobes for Targeted Imaging and Therapy of Gastric Cancer 233
7.2.1 BRCAA1 Antibody-Conjugated FMNPs for Targeted Imaging 233
7.2.2 HAI-178 Antibody-Conjugated FMNPs for Targeted Imaging and Therapy 236
7.2.3 FMNP-Labeled MSCs for Targeted Imaging and Hyperthermia Therapy 237
7.3 Multifunctional QD Probes for Fluorescent Imaging, Genotyping, and Therapy of Gastric Cancer 239
7.3.1 RGD-Conjugated RNase A-Associated dRQDs for Targeted Imaging and Therapy 239
7.3.2 Her2 Antibody-Conjugated RQDs for Targeted Imaging and Therapy of In Situ Gastric Cancer 240
7.3.3 BRCAA1 and Her2 Monoclonal Antibody-Conjugated PQDs for Targeted Imaging and Therapy 241
7.4 Multifunctional Upper Conversion Nanoprobes for Targeted Imaging and Therapy of Gastric Cancer 244
7.4.1 Lanthanide-Doped NaGdF4 Upconversion Nanocrystals for Dual-Mode UCL Imaging and CT Imaging and Targeted Chemical Therapy 245
7.4.2 Folic Acid-Conjugated Silica-Modified Upconversion Nanoprobes for Targeted UCL and CT Imaging 247
7.5 Multifunctional Gold Nanoprobes for Targeted Imaging and Therapy 250
7.5.1 Folic Acid-Conjugated Gold Nanorods for Targeted Imaging and Therapy 253
7.5.2 Cetuximab-Conjugated Gold Nanoparticles for SERS Imaging and Therapy 255
7.5.3 BRCAA1 Antibody-Conjugated Gold Nanoprisms for Targeted Photoacoustic Imaging and Photothermal Therapy 256
7.5.4 CD44v6 Antibody-Conjugated Gold Nanostars for Photoacoustic Imaging and Photothermal Therapy of Gastric Cancer Stem Cells 257
7.5.5 Folic Acid/ce6-Conjugated Gold Nanoclusters for NIR Fluorescent Imaging and Photodynamic Therapy 258
7.5.6 Gold Nanoparticles as a High Efficient siRNA Delivery System 259
7.6 RNA Nanoparticles for Targeted Imaging and siRNA Therapy of Gastric Cancer 261
7.7 Carbon Dot-Based Nanoprobes for Targeted Imaging and Photodynamic Therapy 265
7.8 Dendritic Cell and Tumor Cell Fused Vaccine for Targeted Imaging and Enhanced Immunotherapy of Gastric Cancer 268
7.9 Oral Microcapsule Endoscopy Combined with Nanoprobes for Gastrointestinal Imaging 269
7.10 Clinical Translational Prospects of Multifunctional Nanoprobes 270
7.11 Conclusion Remark 271
References 271
Chapter 8: Functional Nanoparticles for Molecular Imaging-Guided Gene Delivery and Therapy 278
8.1 Introduction 278
8.2 Major Non-radiation Medical Imaging Techniques 281
8.2.1 Magnetic Resonance Imaging (MRI) 281
8.2.2 Optical Imaging 282
8.3 Functionality of Nanoparticles for Imaging-Guided Gene Delivery 283
8.3.1 Stabilization of Nucleic Acid Complexion 283
8.3.2 Stimuli-Triggered Cellular Uptake: Passive and Active Targeting Effect 285
8.3.3 Stimuli-Reducible PEGylation 286
8.3.4 Facilitated Endosomal Escape 287
8.3.5 Controlled Intracellular Localization 288
8.4 Various Functional Nanoparticles and Systems for Molecular Imaging-Guided Gene Therapy 288
8.4.1 Polymer-Based Nanoparticles 288
8.4.2 Dendrimer-Based Nanoparticles 289
8.4.3 Lipid-Based Nanoparticles 290
8.4.4 Iron Oxide Nanoparticles 291
8.4.5 Quantum Dots 293
8.4.6 Other Organic and Inorganic Nanoparticles 295
8.4.6.1 Carbon Nanotubes 295
8.4.6.2 Silica Nanoparticles 297
8.4.6.3 Gold Nanoparticles 298
8.5 Conclusions 301
References 301
Chapter 9: Multifunctional Mesoporous/Hollow Silica for Cancer Nanotheranostics 311
9.1 Introduction 311
9.2 MHSN-Based Fluorescent Optical Imaging (FOI) and Medical Imaging 313
9.2.1 MHSN-Based FOI 313
9.2.2 Medical Imaging 318
9.2.2.1 Ultrasound 319
9.2.2.2 CT 320
9.2.2.3 MRI 321
9.2.2.4 PET 327
9.2.2.5 Photoacoustic Imaging (PAI) 327
9.3 MHSN-Guided Imaging and Therapy for Nanotheranostics 331
9.3.1 Silica-Guided Imaging and Chemotherapy 331
9.3.1.1 Silica-Guided FOI and Chemotherapy 331
9.3.1.2 Silica-Guided Medical Imaging and Chemotherapy 334
9.3.2 Silica-Guided Imaging and Phototherapies 334
9.3.2.1 Silica-Guided Imaging and Photothermal Therapy 336
9.3.2.2 Silica-Guided Imaging and Photodynamic Therapy 338
9.3.3 Integration of Multimodal Imaging and Combination Therapy 341
9.4 Conclusion and Perspective 343
References 344
Chapter 10: Multimodal Micelles for Theranostic Nanomedicine 359
10.1 Introduction 359
10.2 Theranostic Micelles for Imaging and Chemotherapy 360
10.2.1 Micelles for Fluorescent Imaging and Chemotherapy 361
10.2.2 Micelles for MRI and Chemotherapy 362
10.2.3 Micelles for US Imaging and Chemotherapy 365
10.2.4 Micelles for PET and Chemotherapy 367
10.3 Theranostic Micelles for Imaging and Photothermal Therapy 370
10.4 Theranostic Micelles for Imaging and Photodynamic Therapy 372
10.5 Theranostic Micelles for Imaging and Gene Therapy 373
10.6 Theranostic Micelles for Multimodal Imaging and Combination Therapy 375
10.7 Perspectives 379
References 379
Erratum 386