Abstract
Nonviral gene delivery carriers are designed to efficiently deliver genes (nucleic acids) into the targeted cells/tissues in a safe manner. The goal of this thesis is to develop new biodegradable polymer/gold nanocomplex systems to overcome low transfection dfficiency under serum-containing environment ans carrier cytotoxicity. The thesis contains two main parts as describes below: In the first part of the thesis, a biodegradable polymer/gold nanosphere system was prepared using layer-by-layer deposition method and assessed for its gene delivery capability. A biodegradable polymer (SPEI) was synthesized following by the structure characterizations using 1H-NMR. To prepare polymer/gold nanosphere complex, we synthesized gold nanosphere (AuNP) with uniform size distribution. 11-Mercaptoundecanoic acid (MUA) was then used to coated covalently onto the surface of AuNP. SPEI was subsequently deposited on the surface of MUA-AuNP via electrostatic interaction to form SPEI/MUA-AuNP. In order to understand the interactions between the complex and nucleic acids as well as the changes on the material's properties during layer-by-layer process, a series of physicochemical properties were studied. To assess its gene transfection capability on mammalian cells, both fluorescence gene and luciferase gene were utilized as the transgene expression reporting system. The results show that SPEI/MUA-AuNP is capable of interacting and delivering the designated genes into the cells. It is worth mentioning that the transfection efficiency of SPEI/MUA-AuNP was significantly higher than the commercial PEI25K under serum-containing environment. Importantly, SPEI/MUA-AuNP resulted in significantly lower cytotoxicity comparing to PEI25K. Taken these results together, it is anticipated that this biodegradable polymer/gold nanocomplex system has good potential on nonviral gene therapy. In the second part of the thesis, gold nanorods (AuNR) with surface-bound low molecular weight PEI800 were synthesized and tested for the gene delivery performance. First, thiol group-bearing PEI800 (PEI800-SH) was synthesized by a ring-opening reaction. PEI800-SH was then used to assemble onto the surface of AuNR via gold-thiol covalent bonding to afford AuNR-S-PEI800 with nucleic acid-binding ability. AuNR-S-PEI800 was subsequently characterized by a series of physicochemical properties. Finally, the cellular uptake/distribution, gene transfection efficiency and cytocompatibility were investigated and the results suggest that AuNR-S-PEI800 posses well dispersity, low cytotoxicity and efficient gene transfection on mammalian cells.