声明
Certificate of authenticity
Summary
摘要
Table of Contents
CHAPTER(1)Introduction
1.1.1.RNA interference and siRNA therapy
1.1.2.Nucleic acids and clinical progress
1.2 Delivery of siRNA
1.2.1.Challenges in siRNA delivery
1.3 Nanocarriers for siRNA delivery
1.3.1.challenges to the delivery of nanocarriers
1.4.Physicochemical considerations for the design of nucleic acid nanocarriers
1.4.1.Influence of nanocarriers properties on the detivery of nucleic acids
1.4.2.Improving design of nanocarriers
1.5.Summary and dissertation objectives
References
CHAPTER(2)Influence of surface charge of lipid-assisted nanocarriers on siRNA delivery
2.1.Introduction
2.2.Materials and methods
2.2.1.Materials,cell lines,and animals
2.2.2.Synthesis of cationic lipid
2.2.3.Preparation,charge tuning and characterization of nanoparticles encapsulating siRNA
2.2.4.Preparation,charge tuning and characterization of nanoparticles encapsulating FRET dyes
2.2.5.Stability of NPs in simulated and physiological fluids
2.2.7.In vitro cellular uptake by macrophages
2.2.8.In vitro gene silencing in macrophages
2.2.9.In vivo accumulation of the NPs in inflamed colons
2.2.10.In vivo therapy against acute UC
2.2.11.Statistical analysis
2.3.Results and Discussion
2.3.1.Lipid synthesis
2.3.2.NP preparation,charge tuning,and characterization
2.3.3.Structural stability of NPs and siRNA integrity
2.3.4.In vitro cellular uptake
2.3.5.In vitro silencing in macrophages
2.3.6.Accumulation in inflamed colons
2.3.7.In vivo silencing in acute UC
2.4.Summary
References
CHAPTER(3)Influence of lipid structure on siRNA delivery by lipid assisted nanocarriers
3.1.Introduction
3.2.1.Materials
3.2.2.Synthesis of cholesterol based lipids
3.2.3.Synthesis of alkyl chain based lipids
3.2.4.Design and fabrication of a microfIuidic device
3.2.5.Synthesis and characterization of nanoparticles by microfluidics
3.3.Results and Discussion
3.3.1.Characterization of cholesterol based lipids
3.3.2.Characterization of alkyl chain based lipids
3.3.3.Preparation and characterization of nanoparticles
3.4.Summary
References
Appendix
Acknowledgements
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