Design and evaluation of lipid based delivery systems for delivery of small molecules and macro-molecular nucleotides based therapeutic agents .

摘要

The objective of this dissertation research was to develop lipid based systems for delivery of small molecules and macro-molecular nucleotides based therapeutic agents, and to evaluate their biological activities in vitro and in vivo. Novel approaches have been utilized to develop passive targeting, active targeting and physical targeting strategies to deliver therapeutic agents. Chapters 2 and 3 contribute scientifically to the field of receptor-mediated delivery systems, with development of anti-EGFR immunoliposomes. Chapter 4 contributes to the gene delivery field, with development of novel cationic lipid coated magnetic vectors that can mediate rapid and efficient gene transfer in vitro in the presence of a magnetic field. Chapter 5 demonstrates that folate-LPDII vectors encapsulating plasmid DNA induced significant cytokine expression, which may contribute to the low in vivo transgene efficiency. Chapter 6 contributes to the field of cancer immunotherapy, with development of lipid nanoparticles (LNPs) encapsulating G3139, a CpG motif containing oligonucleotide. The study exhibited that G3139-LNP could activate both innate and acquired immunity, inhibit tumor growth and even induce complete tumor regression in some mice in a non-anti-bcl2 manner. A more complete understanding of cancer immunosurveillance induced by G3139-LNP is needed for future development of more rational and effective therapeutic strategies.