| Summary | 第6-7页 |
| 摘要 | 第8-13页 |
| CHAPTER (1) Introduction | 第13-33页 |
| 1.1. Prospects of gene delivery | 第13-19页 |
| 1.1.1. RNA interference and siRNA therapy | 第14-17页 |
| 1.1.2. Nucleic acids and clinical progress | 第17-19页 |
| 1.2 Delivery of siRNA | 第19-21页 |
| 1.2.1. Challenges in siRNA delivery | 第19-21页 |
| 1.3 Nanocarriers for siRNA delivery | 第21-23页 |
| 1.3.1. Challenges to the delivery of nanocarriers | 第22-23页 |
| 1.4. Physicochemical considerations for the design of nucleic acid nanocarriers | 第23-26页 |
| 1.4.1. Influence of nanocarriers properties on the delivery of nucleic acids | 第24-25页 |
| 1.4.2. Improving design of nanocarriers | 第25-26页 |
| 1.5. Summary and dissertation objectives | 第26-28页 |
| References | 第28-33页 |
| CHAPTER (2) Influence of surface charge of lipid-assisted nanocarriers on siRNA delivery | 第33-70页 |
| 2.1. Introduction | 第33-35页 |
| 2.2. Materials and methods | 第35-44页 |
| 2.2.1. Materials,cell lines,and animals | 第35-37页 |
| 2.2.2. Synthesis of cationic lipid | 第37页 |
| 2.2.3. Preparation, charge tuning and characterization of nanoparticles encapsulating siRNA | 第37-38页 |
| 2.2.4. Preparation, charge tuning and characterization of nanoparticles encapsulating FRETdyes | 第38-39页 |
| 2.2.5. Stability of NPs in simulated and physiological fluids | 第39页 |
| 2.2.6. The integrity of siRNA in simulated and physiological fluids | 第39-40页 |
| 2.2.7. In vitro cellular uptake by macrophages | 第40-41页 |
| 2.2.8. In vitro gene silencing in macrophages | 第41-42页 |
| 2.2.9. In vivo accumulation of the NPs in inflamed colons | 第42-43页 |
| 2.2.10. In vivo therapy against acute UC | 第43-44页 |
| 2.2.11. Statistical analysis | 第44页 |
| 2.3. Results and Discussion | 第44-63页 |
| 2.3.1. Lipid synthesis | 第44-46页 |
| 2.3.2. NP preparation, charge tuning, and characterization | 第46-48页 |
| 2.3.3. Structural stability of NPs and siRNA integrity | 第48-52页 |
| 2.3.4. In vitro cellular uptake | 第52-54页 |
| 2.3.5. In vitro silencing in macrophages | 第54-56页 |
| 2.3.6. Accumulation in inflamed colons | 第56-58页 |
| 2.3.7 In vivo silencing in acute UC | 第58-63页 |
| 2.4. Summary | 第63-65页 |
| References | 第65-70页 |
| CHAPTER (3) Influence of lipid structure on siRNA delivery by lipid assisted nanocarriers | 第70-97页 |
| 3.1. Introduction | 第70-72页 |
| 3.2. Materials and methods | 第72-84页 |
| 3.2.1. Materials | 第72-73页 |
| 3.2.2. Synthesis of cholesterol based lipids | 第73-81页 |
| 3.2.3. Synthesis of alkyl chain based lipids | 第81页 |
| 3.2.4. Design and fabrication of a microfluidic device | 第81-83页 |
| 3.2.5. Synthesis and characterization of nanoparticles by microfluidics | 第83-84页 |
| 3.3. Results and Discussion | 第84-93页 |
| 3.3.1. Characterization of cholesterol based lipids | 第84-90页 |
| 3.3.2. Characterization of alkyl chain based lipids | 第90-91页 |
| 3.3.3. Preparation and characterization of nanoparticles | 第91-93页 |
| 3.4. Summary | 第93-94页 |
| References | 第94-97页 |
| Appendix Ⅰ Equipments | 第97-100页 |
| Appendix Ⅱ Reagents | 第100-102页 |
| Appendix Ⅲ Solutions and Buffers Preparation | 第102-105页 |
| Appendix Ⅳ Methods and test conditions | 第105-110页 |
| Acknowledgements | 第110-113页 |
| Publications | 第113页 |
