Main description:

Here, front-line researchers in the booming field of nanobiotechnology describe the most promising approaches for bioinspired drug delivery, encompassing small molecule delivery, delivery of therapeutic proteins and gene delivery. The carriers surveyed include polymeric, proteinaceous and lipid systems on the nanoscale, with a focus on their adaptability for different cargoes and target tissues. Thanks to the broad coverage of carriers as well as cargoes discussed, every researcher in the field will find valuable information here.

Contents:

List of Contributors XIII Preface XIX 1 Backbone Degradable and Coiled-Coil Based Macromolecular Therapeutics 1 Jiyuan Yang and Jindoich Kopeeek 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 Factors That Need Attention 2 1.2.2.1 Design of Conjugates for the Treatment of Noncancerous Diseases 2 1.2.2.2 Combination Therapy Using Polymer-Bound Therapeutics 3 1.2.2.3 New Targeting Strategies 4 1.2.2.4 Relationship Between Detailed Structure of the Conjugates and Their 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 Trafficking 7 1.2.2.7 Relationship Between the Molecular Weight of the Carrier and the Efficacy 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 Therapeutics 10 1.2.4 Summary of Part 2 and Future Prospects 14 1.3 Drug-Free Macromolecular Therapeutics 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 Macromolecular Therapeutics: Design, In Vitro, and In Vivo Activity 17 1.3.4 Potential, Limitations, and Future Prospect of Drug-Free Macromolecular Therapeutics 18 1.4 General Summary and Outlook 20 Acknowledgments 21 References 21 2 Dendritic Polymers as Targeting Nanoscale Drug Delivery Systems for Cancer Therapy 29 Kui Luo and Zhongwei Gu 2.1 Introduction 29 2.2 Functional Dendritic Polymers Based Drug Delivery Vehicles for Targeting Tumor Therapy via EPR Effect 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 Cancer Therapy 45 2.4 Conclusion 54 References 54 3 Composite Colloidal Nanosystems for Targeted Delivery and Sensing 61 Pilar Rivera Gil, Moritz Nazarenus, and Wolfgang 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 Particle Size of Micelles 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 Wenping Wang and Kinam Park 5.1 Introduction 109 5.2 Commonly Used Biomimetic Polymers and Their Applications in DDS 110 5.2.1 Polylactones and Their Modifications 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( -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 from Protein-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 Emulsification 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-Specific 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 Gene Therapy and Gene Carriers 171 7.1.1 Gene Therapy 171 7.1.1.1 The Concept of Gene Therapy 171 7.1.1.2 Development and the Present Situation of Gene Therapy 171 7.1.1.3 Methods and Strategies of Gene Therapy 172 7.1.1.4 Research Contents and Challenges of Gene Therapy 174 7.1.2 Gene Carriers 175 7.1.2.1 The Concept of Gene Carrier 175 7.1.2.2 The Necessity of the Gene Carrier 175 7.1.2.3 Requirements of Gene Carrier 176 7.1.2.4 Classification 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 Modification Polymeric Gene Carriers 183 7.3.1 Amino Acid Derivatives Modified Polymeric Gene Carriers 183 7.3.1.1 Poly(glutamic acid) Derivatives Modified PEI 184 7.3.1.2 Polyphenylalanine Derivatives Modified PEI 186 7.3.2 PEG Modified Hyperbranched PEI 187 7.4 Low Molecular Weight (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 Rujiang Ma 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-Qiong Mao, Jin-Zhi Du, Xian-Zhu Yang, and Jun Wang 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 Thermo-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