先进功能材料丛书 生物启发与仿生型高分子药物及基因递送系统 英文版
作者：顾忠伟 主编
出版时间：2015年版
内容简介
近年来，生物活性物质控释系统的研究主要集中于：时控型药物控释系统；自调节药物控释系统；靶 药物控释系统；组织/细胞微环境响应性药物控释系统以及核酸类药物递送系统。受自然界启发，如何运用仿生的方法构建和优化药物、蛋白质和基因的递送系统已是一个新兴的发展方向和趋势，它是涉及生物学、材料学、化学、物理学、药学、工程学等学科的多学科交叉研究领域。本书汇聚了包括美国工程院院士在内的多名国内外药物控释系统研究领域的著名科学家近年来的最新研究工作。作为国际上第一本生物启发和仿生高分子的药物及基因递送系统的专著，本书不仅报道了药物递送领域的最新进展和未来发展方向，还分别从材料与细胞相互作用、载体材料的组织/细胞微环境响应性设计、控释系统在体内环境下生物活性物质的高效释放及有效表达等不同的角度对药物递送系统的未来发展方向进行了新的诠释和展望，充分体现了前瞻性和新颖性，是该领域一部难得的、非常有价值的专著。本书可供从事生物工程、纳米技术及材料领域的高校、科研院所、公司企业的相关研究人员使用。同时可作为生物医学工程、高分子科学及相关交叉学科的研究生及本科生教学参考书。
目录
List of Contributors XIII
Preface XIX
1 Backbone Degradable and Coiled-Coil Based Macromolecular
Therapeutics 1
Jiyuan Yang and Jindˇ rich Kopeˇ cek
1.1 Introduction 1
1.2 Water-Soluble Polymers as Carriers of Anticancer Drugs 2
1.2.1 First Generation Conjugates – Design, Synthesis, and Activity 2
1.2.2 Analysis of Design Factorshat Need Attention 2
1.2.2.1 Design of Conjugates for the Treatment of Noncancerous
Diseases 2
1.2.2.2 Combinationherapy Using Polymer-Boundherapeutics 3
1.2.2.3 New Targeting Strategies 4
1.2.2.4 Relationship Between Detailed Structure of the Conjugates andheir
Properties 5
1.2.2.5 Impact of Binding a Drug to a Polymer on the Mechanism of
Action 6
1.2.2.6 Mechanism of Internalization and Subcellular Tra?cking 7
1.2.2.7 Relationship Between the MolecularWeight of the Carrier and the
E?cacy of the Conjugate 7
1.2.3 Design of Second Generation Conjugates – Long-Circulating and
Backbone Degradable 8
1.2.3.1 RAFT Copolymerization for the Synthesis of Conjugates 8
1.2.3.2 Click Reactions for Chain Extension into Multiblock
Copolymers 10
1.2.3.3 Biological Properties of Long-Circulating Macromolecular
herapeutics 10
1.2.4 Summary of Part 2 and Future Prospects 14
1.3 Drug-Free Macromolecularherapeutics – A New Paradigm in
Drug Delivery 15
1.3.1 Biorecognition in Hybrid Polymer Systems 15
1.3.2 Coiled-Coils in Biomedical Systems 16
1.3.3 Coiled-Coil Based Drug-Free Macromolecularherapeutics: Design,
In Vitro,and In Vivo Activity 17
1.3.4 Potential, Limitations, and Future Prospect of Drug-Free
Macromolecularherapeutics 18
1.4 General Summary and Outlook 20
Acknowledgments 21
References 21
2 Dendritic Polymers as Targeting Nanoscale Drug Delivery Systems
forCancerTherapy 29
Kui Luo and Zhongwei Gu
2.1 Introduction 29
2.2 Functional Dendritic Polymers Based Drug Delivery Vehicles for
Targeting Tumorherapy via EPR E?ect 30
2.2.1 Functional Dendritic Polymers for Encapsulation of Anticancer
Drugs 32
2.2.2 Chemical Conjugation Functional Dendritic Polymers as Drug
Delivery Systems 37
2.3 Tumor Targeting Moieties Functionalized Dendritic Drug Delivery
Vehicles for Cancerherapy 45
2.4 Conclusion 54
References 54
3 Composite Colloidal Nanosystems for Targeted Delivery
and Sensing 61
Pilar Rivera Gil,Moritz Nazarenus, andWolfgang J. Parak
3.1 Introduction 61
3.1.1 Working Toolkit 62
3.1.2 Engineering a Multifunctional Carrier 63
3.2 Objective 66
3.3 Cellular Behavior of the Carrier 66
3.3.1 Intracellular Fate 66
3.3.2 Biocompatibility 69
3.4 Applications 71
3.4.1 Delivery with Multifunctional PEM Capsules 71
3.4.1.1 Magnetic Targeting and Magnetofection 71
3.4.1.2 Strategies for Controlled Opening 73
3.4.2 Intracellular Ion Sensing 75
3.5 Conclusions 77
Abbreviations 77
References 78
4 Polymeric Micelles for Cancer-Targeted Drug Delivery 85
Huabing Chen, Zhishen Ge, and Kazunori Kataoka
4.1 Introduction 85
4.2 Micelle Formulations in Clinical Development 85
4.3 ParticleSizeofMicelles 89
4.4 Morphology of Micelles 92
4.5 Targeting Design of Micelles for Enhanced Accumulation and Cell
Internalization 94
4.6 Functional Designs of Micelles 96
4.7 Design of Micelles for Gene Delivery 99
4.8 Challenge and Future Perspective 103
References 104
5 Biomimetic Polymers for In Vivo Drug Delivery 109
WenpingWang and KinamPark
5.1 Introduction 109
5.2 Commonly Used Biomimetic Polymers andheir Applications
in DDS 110
5.2.1 Polylactones andheir Modi?cations 110
5.2.1.1 Poly(lactic acid) (PLA) 110
5.2.1.2 Poly(lactic-co-glycolic acid) (PLGA) 113
5.2.1.3 Poly(ε-caprolactone) (PCL) 118
5.2.2 Dendrimer 124
5.2.2.1 Structure and Properties of Dendrimers 124
5.2.2.2 Types of Dendrimers 124
5.2.2.3 Applications of Dendrimers as Carriers in Drug Delivery
Systems 124
5.2.3 Synthetic Polypeptides 134
5.3 Challenges and Perspectives 135
References 136
6 Drug Delivery fromProtein-Based Nanoparticles 149
Dan Ding and Xiqun Jiang
6.1 Introduction 149
6.2 Preparation of Protein-Based Nanoparticles 150
6.2.1 Desolvation 150
6.2.2 Emulsi?cation 151
6.2.3 Coacervation 151
6.2.4 Polymer–Monomer Pair Reaction System 151
6.3 Drug Delivery from Albumin-Based Nanoparticles 152
6.3.1 Albumin-Based Nanoparticles as Drug Carriers 152
6.3.2 Targeting Ligand-Functionalized Albumin-Based
Nanoparticles 154
6.3.3 Nanoparticle Albumin-Bound (nab)Technology 156
6.4 Drug Delivery from Gelatin-Based Nanoparticles 156
6.4.1 Gelatin-Based Nanoparticles as Drug Carriers 158
6.4.2 Targeting Ligand-Functionalized Gelatin-Based Nanoparticles 160
6.4.3 Site-Speci?c Drug Delivery System 162
6.5 Drug Delivery from Other Protein-Based Nanoparticles 163
References 165
7 Polymeric Gene Carriers 171
Xuesi Chen, Huayu Tian, and Xiuwen Guan
7.1 Geneherapy and Gene Carriers 171
7.1.1 Geneherapy 171
7.1.1.1 he Concept of Geneherapy 171
7.1.1.2 Development and the Present Situation of Geneherapy 171
7.1.1.3 Methods and Strategies of Geneherapy 172
7.1.1.4 Research Contents and Challenges of Geneherapy 174
7.1.2 Gene Carriers 175
7.1.2.1 he Concept of Gene Carrier 175
7.1.2.2 he Necessity of the Gene Carrier 175
7.1.2.3 Requirements of Gene Carrier 176
7.1.2.4 Classi?cation of Gene Carrier 176
7.2 Polymeric Gene Carriers 178
7.2.1 Cationic Polymer Gene Carriers 178
7.2.1.1 Process of the Polycation Vector Mediated Gene Delivery 179
7.2.1.2 Categories and Research Situation of the Cationic Polymer Gene
Vector 180
7.3 PEI Grafting Modi?cation Polymeric Gene Carriers 183
7.3.1 Amino Acid Derivatives Modi?ed Polymeric Gene Carriers 183
7.3.1.1 Poly(glutamic acid) Derivatives Modi?ed PEI 184
7.3.1.2 Polyphenylalanine Derivatives Modi?ed PEI 186
7.3.2 PEG Modi?ed Hyperbranched PEI 187
7.4 Low MolecularWeight (LWM) PEI Base Polymeric Gene
Carriers 188
7.4.1 Crosslinked Polycations 188
7.4.1.1 Crosslinked Polycation OEI-CBA 188
7.4.1.2 Crosslinked Polycation OEI-PBLG-PEGDA 189
7.4.1.3 Hexachlorotriphosphazene Crosslinked Polycation 190
7.4.2 Grafted Polycations 190
7.4.2.1 Grafted Cationic Polymer MP-g-OEI 190
7.4.2.2 Graft Cationic Polymer N-PAE-g-OEI 191
7.4.2.3 Graft Cationic Polymer mPEG-b-PMCC-g-OEI 192
7.5 Targeted Shielding System for Polymeric Gene Carriers 192
7.5.1 Static Shielding System 192
7.5.1.1 Poly(glutamine acid) Shielding System and PEGylations 195
7.5.1.2 Sulfonamides Related Shielding System 195
7.5.2 Other Design Strategies of Cationic Gene Carrier 196
7.6 Conclusion 197
References 197
8 pH-Sensitive Polymeric Nanoparticles as Carriers for Cancer Therapy
and Imaging 203
Yi Li, Guang Hui Gao, Ick Chan Kwon, and Doo Sung Lee
8.1 Introduction 203
8.2 pH-Sensitive Polymers 204
8.2.1 pH-Sensitive Anionic Polymers 205
8.2.2 pH-Sensitive Cationic Polymers 207
8.2.3 pH-Sensitive Neutral Polymers 208
8.3 pH-Sensitive Polymers as Drug Carriers 209
8.3.1 pH-Sensitive Polymer–Drug Conjugates 210
8.3.2 pH-Sensitive Polymeric Micelles 210
8.3.3 pH-Sensitive Polymersomes 212
8.3.4 pH-Sensitive Polymer–Inorganic Hybrid Nanoparticles 214
8.3.5 pH-Sensitive Dendrimers 214
8.4 pH-Sensitive Polymers for Bioimaging 215
8.5 Conclusions 216
References 216
9 Charge-Reversal Polymers for Biodelivery 223
Bo Zhang, KaiWang, Jingxing Si,Meihua Sui, and Youqing Shen
9.1 Applications of Cationic Polymers in Biodelivery 223
9.2 Barriers for Cationic Polymers in In vitro and In vivo
Applications 224
9.3 Characteristic pH Gradients in Tumor Interstitium and
Endo/Lysosomes 225
9.4 Chemistry of Charge-Reversal Polymers Based on Acid-Labile
Amides 226
9.4.1 pHe-Triggered Charge-Reversal 228
9.4.2 pHL-Triggered Charge-Reversal 229
9.5 Applications of Charge-Reversal Polymers in Biodelivery
Systems 230
9.5.1 Charge-Reversal in Cancer Drug Delivery 230
9.5.2 Charge-Reversal in Gene Delivery 232
9.5.3 Charge-Reversal in Protein Delivery 235
9.5.4 Charge-Reversal Incorporated with Inorganic Materials 236
9.6 Perspectives 237
References 237
10 Phenylboronic Acid-Containing Glucose-Responsive Polymer
Materials: Synthesis and Applications in Drug Delivery 243
RujiangMa and Linqi Shi
10.1 Introduction 243
10.2 PBA-Containing Polymers Operating Under Physiological
Conditions 244
10.3 Chemically Crosslinked PBA-Based Gels 247
10.4 Self-Assembled PBA-Based Polymer Micelles 253
10.5 Self-Assembled PBA-Based Polymersomes 266
10.6 Perspectives 271
References 272
11 Extracellular pH-Activated Nanocarriers for Enhanced Drug
Delivery to Tumors 277
You-Yong Yuan, Cheng-QiongMao, Jin-Zhi Du, Xian-Zhu Yang,
and JunWang
11.1 Introduction 277
11.2 Passive and Active Tumor Targeting 278
11.3 Targeting the Extracellular pH (pHe) in Tumors 279
11.4 Extracellular pH-Induced Drug Delivery to Tumors 280
11.5 Ligand Exposure by a Shielding/Deshielding Method 281
11.6 Surface Charge Reversing Nanoparticles 283
11.6.1 Enhanced Cellular Uptake by Surface Charge Reversing
Nanoparticles 283
11.6.2 Overcoming MDR by Surface Charge Reversing Nanoparticles 287
11.6.3 Enhanced Delivery of siRNA by Surface-Charge Reversing
Nanoparticles 295
11.7 Conclusion 300
References 300
12 Stimulation-Sensitive Drug Delivery Systems 305
Xintao Shuai and Du Cheng
12.1 Introduction 305
12.2 pH-Sensitive Delivery Systems 306
12.2.1 pH-Sensitive Micellar Delivery Systems 306
12.2.2 pH-Sensitive Polymer–Drug Conjugates 307
12.2.3 pH-Sensitive Dendrimers 308
12.2.4 pH-Sensitive Liposomes 310
12.3 hermo-Sensitive Delivery Systems 311
12.4 Biomolecule-Sensitive Delivery Systems 314
12.4.1 Enzyme-Sensitive Nanocarriers 315
12.4.2 Reduction–Responsive Conjugates 316
12.5 Other Environmentally Sensitive Nanocarriers 318
12.6 Outlook 319
References 320
Index 331
