白蛋白等天然或仿生衍化载体是过去几年中药物和治疗分子智能递送系统中发展最成功的例子。顾忠伟主编的《生物启发与仿生型高分子药物及基因递送系统》一书中，活跃在蓬勃发展的纳米生物技术领域的一线研究人员描述了最有前途的生物启发与仿生高分子的药物及基因递送方法，包括小分子、治疗蛋白以及基因的递送。涉及的载体为纳米尺度高分子、蛋白质和脂质体，并聚焦于其对不同治疗分子以及靶向组织的适用性。

本书适用于医学、药学、生物技术、材料科学相关的研究人员以及制药界人士。

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；靶向药物控释系统；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。

顾忠伟主编的这本《生物启发与仿生型高分子药物及基因递送系统》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。

List of Contributors

Preface

1 Backbone Degradable and Coiled-Coil Based Macromolecular Therapeutics

Jiyuan Yang and Jindrich Kopecek

 1.1 Introduction

 1.2 Water-Soluble Polymers as Carriers of Anticancer Drugs

1.2.1 First Generation Conjugates – Design, Synthesis, and Activity

1.2.2 Analysis of Design Factorshat Need Attention

 1.2.2.1 Design of Conjugates for the Treatment of Noncancerous Diseases

 1.2.2.2 Combinationherapy Using Polymer-Boundherapeutics

 1.2.2.3 New Targeting Strategies

 1.2.2.4 Relationship Between Detailed Structure of the Conjugates andheir Properties

 1.2.2.5 Impact of Binding a Drug to a Polymer on the Mechanism of Action

 1.2.2.6 Mechanism of Internalization and Subcellular Trafficking

 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

 1.2.3.1 RAFT Copolymerization for the Synthesis of Conjugates

 1.2.3.2 Click Reactions for Chain Extension into Multiblock Copolymers

 1.2.3.3 Biological Properties of Long-Circulating Macromolecular herapeutics

1.2.4 Summary of Part 2 and Future Prospects

 1.3 Drug-Free Macromolecularherapeutics – A New Paradigm in Drug Delivery

1.3.1 Biorecognition in Hybrid Polymer Systems

1.3.2 Coiled-Coils in Biomedical Systems

1.3.3 Coiled-Coil Based Drug-Free Macromolecularherapeutics: Design, In Vitro,and In Vivo Activity

1.3.4 Potential, Limitations, and Future Prospect of Drug-Free Macromolecularherapeutics

 1.4 General Summary and Outlook

 Acknowledgments

 References

2 Dendritic Polymers as Targeting Nanoscale Drug Delivery Systems for Cancer Therapy

Kui Luo and Zhongwei Gu

 2.1 Introduction

 2.2 Functional Dendritic Polymers Based Drug Delivery Vehicles for Targeting Tumorherapy via EPR Effect

2.2.1 Functional Dendritic Polymers for Encapsulation of Anticancer Drugs

2.2.2 Chemical Conjugation Functional Dendritic Polymers as Drug Delivery Systems

 2.3 Tumor Targeting Moieties Functionalized Dendritic Drug Delivery Vehicles for Cancerherapy

 2.4 Conclusion

 References

3 Composite Colloidal Nanosystems for Targeted Delivery and Sensing

Pilar Rivera Gil,Moritz Nazarenus, andWolfgang J. Parak

 3.1 Introduction

3.1.1 Working Toolkit

3.1.2 Engineering a Multifunctional Carrier

 3.2 Objective

 3.3 Cellular Behavior of the Carrier

3.3.1 Intracellular Fate

3.3.2 Biocompatibility

 3.4 Applications

3.4.1 Delivery with Multifunctional PEM Capsules

3.4.1.1 Magnetic Targeting and Magnetofection

3.4.1.2 Strategies for Controlled Opening

3.4.2 Intracellular Ion Sensing

 3.5 Conclusions

 Abbreviations

 References

4 Polymeric Micelles for Cancer-Targeted Drug Delivery

Huabing Chen, Zhishen Ge, and Kazunori Kataoka

 4.1 Introduction

 4.2 Micelle Formulations in Clinical Development

 4.3 ParticleSizeofMicelles

 4.4 Morphology of Micelles

 4.5 Targeting Design of Micelles for Enhanced Accumulation and Cell Internalization

 4.6 Functional Designs of Micelles

 4.7 Design of Micelles for Gene Delivery

 4.8 Challenge and Future Perspective

 References

5 Biomimetic Polymers for In Vivo Drug Delivery

WenpingWang and KinamPark

 5.1 Introduction

 5.2 Commonly Used Biomimetic Polymers andheir Applications in DDS

5.2.1 Polylactones andheir Modifications

 5.2.1.1 Poly(lactic acid) (PLA)

 5.2.1.2 Poly(lactic-co-glycolic acid) (PLGA)

 5.2.1.3 Poly(ε-caprolactone) (PCL)

5.2.2 Dendrimer

 5.2.2.1 Structure and Properties of Dendrimers

 5.2.2.2 Types of Dendrimers

 5.2.2.3 Applications of Dendrimers as Carriers in Drug Delivery Systems

5.2.3 Synthetic Polypeptides

 5.3 Challenges and Perspectives

 References

6 Drug Delivery fromProtein-Based Nanoparticles

Dan Ding and Xiqun Jiang

 6.1 Introduction

 6.2 Preparation of Protein-Based Nanoparticles

6.2.1 Desolvation

6.2.2 Emulsification

6.2.3 Coacervation

6.2.4 Polymer–Monomer Pair Reaction System

 6.3 Drug Delivery from Albumin-Based Nanoparticles

6.3.1 Albumin-Based Nanoparticles as Drug Carriers

6.3.2 Targeting Ligand-Functionalized Albumin-Based Nanoparticles

6.3.3 Nanoparticle Albumin-Bound (nab)Technology

 6.4 Drug Delivery from Gelatin-Based Nanoparticles

6.4.1 Gelatin-Based Nanoparticles as Drug Carriers

6.4.2 Targeting Ligand-Functionalized Gelatin-Based Nanoparticles

6.4.3 Site-Speci?c Drug Delivery System

 6.5 Drug Delivery from Other Protein-Based Nanoparticles

 References

7 Polymeric Gene Carriers

Xuesi Chen, Huayu Tian, and Xiuwen Guan

 7.1 Geneherapy and Gene Carriers

7.1.1 Geneherapy

 7.1.1.1 he Concept of Geneherapy

 7.1.1.2 Development and the Present Situation of Geneherapy

 7.1.1.3 Methods and Strategies of Geneherapy

 7.1.1.4 Research Contents and Challenges of Geneherapy

7.1.2 Gene Carriers

 7.1.2.1 he Concept of Gene Carrier

 7.1.2.2 he Necessity of the Gene Carrier

 7.1.2.3 Requirements of Gene Carrier

 7.1.2.4 Classi?cation of Gene Carrier

 7.2 Polymeric Gene Carriers

7.2.1 Cationic Polymer Gene Carriers

 7.2.1.1 Process of the Polycation Vector Mediated Gene Delivery

 7.2.1.2 Categories and Research Situation of the Cationic Polymer Gene Vector

 7.3 PEI Grafting Modi?cation Polymeric Gene Carriers

7.3.1 Amino Acid Derivatives Modi?ed Polymeric Gene Carriers

 7.3.1.1 Poly(glutamic acid) Derivatives Modified PEI

 7.3.1.2 Polyphenylalanine Derivatives Modified PEI

7.3.2 PEG Modi?ed Hyperbranched PEI

 7.4 Low MolecularWeight (LWM) PEI Base Polymeric Gene Carriers

7.4.1 Crosslinked Polycations

 7.4.1.1 Crosslinked Polycation OEI-CBA

 7.4.1.2 Crosslinked Polycation OEI-PBLG-PEGDA

 7.4.1.3 Hexachlorotriphosphazene Crosslinked Polycation

7.4.2 Grafted Polycations

 7.4.2.1 Grafted Cationic Polymer MP-g-OEI

 7.4.2.2 Graft Cationic Polymer N-PAE-g-OEI

 7.4.2.3 Graft Cationic Polymer mPEG-b-PMCC-g-OEI

 7.5 Targeted Shielding System for Polymeric Gene Carriers

7.5.1 Static Shielding System

 7.5.1.1 Poly(glutamine acid) Shielding System and PEGylations

 7.5.1.2 Sulfonamides Related Shielding System

7.5.2 Other Design Strategies of Cationic Gene Carrier

 7.6 Conclusion

 References

8 pH-Sensitive Polymeric Nanoparticles as Carriers for Cancer Therapy and Imaging

Yi Li, Guang Hui Gao, Ick Chan Kwon, and Doo Sung Lee

 8.1 Introduction

 8.2 pH-Sensitive Polymers

8.2.1 pH-Sensitive Anionic Polymers

8.2.2 pH-Sensitive Cationic Polymers

8.2.3 pH-Sensitive Neutral Polymers

 8.3 pH-Sensitive Polymers as Drug Carriers

8.3.1 pH-Sensitive Polymer–Drug Conjugates

8.3.2 pH-Sensitive Polymeric Micelles

8.3.3 pH-Sensitive Polymersomes

8.3.4 pH-Sensitive Polymer–Inorganic Hybrid Nanoparticles

8.3.5 pH-Sensitive Dendrimers

 8.4 pH-Sensitive Polymers for Bioimaging

 8.5 Conclusions

 References

9 Charge-Reversal Polymers for Biodelivery

Bo Zhang, KaiWang, Jingxing Si,Meihua Sui, and Youqing Shen

 9.1 Applications of Cationic Polymers in Biodelivery

 9.2 Barriers for Cationic Polymers in In vitro and In vivo Applications

 9.3 Characteristic pH Gradients in Tumor Interstitium and Endo/Lysosomes

 9.4 Chemistry of Charge-Reversal Polymers Based on Acid-Labile Amides

9.4.1 pHe-Triggered Charge-Reversal

9.4.2 pHL-Triggered Charge-Reversal

 9.5 Applications of Charge-Reversal Polymers in Biodelivery Systems

9.5.1 Charge-Reversal in Cancer Drug Delivery

9.5.2 Charge-Reversal in Gene Delivery

9.5.3 Charge-Reversal in Protein Delivery

9.5.4 Charge-Reversal Incorporated with Inorganic Materials

 9.6 Perspectives

 References

10 Phenylboronic Acid-Containing Glucose-Responsive Polymer

 Materials: Synthesis and Applications in Drug Delivery

 RujiangMa and Linqi Shi

 10.1 Introduction

 10.2 PBA-Containing Polymers Operating Under Physiological Conditions

 10.3 Chemically Crosslinked PBA-Based Gels

 10.4 Self-Assembled PBA-Based Polymer Micelles

 10.5 Self-Assembled PBA-Based Polymersomes

 10.6 Perspectives

 References

11 Extracellular pH-Activated Nanocarriers for Enhanced Drug Delivery to Tumors

You-Yong Yuan, Cheng-QiongMao, Jin-Zhi Du, Xian-Zhu Yang, and JunWang

 11.1 Introduction

 11.2 Passive and Active Tumor Targeting

 11.3 Targeting the Extracellular pH (pHe) in Tumors

 11.4 Extracellular pH-Induced Drug Delivery to Tumors

 11.5 Ligand Exposure by a Shielding/Deshielding Method

 11.6 Surface Charge Reversing Nanoparticles

11.6.1 Enhanced Cellular Uptake by Surface Charge Reversing Nanoparticles

11.6.2 Overcoming MDR by Surface Charge Reversing Nanoparticles

11.6.3 Enhanced Delivery of siRNA by Surface-Charge Reversing Nanoparticles

 11.7 Conclusion

 References

12 Stimulation-Sensitive Drug Delivery Systems

Xintao Shuai and Du Cheng

 12.1 Introduction

 12.2 pH-Sensitive Delivery Systems

12.2.1 pH-Sensitive Micellar Delivery Systems

12.2.2 pH-Sensitive Polymer–Drug Conjugates

12.2.3 pH-Sensitive Dendrimers

12.2.4 pH-Sensitive Liposomes

 12.3 hermo-Sensitive Delivery Systems

 12.4 Biomolecule-Sensitive Delivery Systems

12.4.1 Enzyme-Sensitive Nanocarriers

12.4.2 Reduction–Responsive Conjugates

 12.5 Other Environmentally Sensitive Nanocarriers

 12.6 Outlook

 References

Index