| Since the development of gene therapy, a variety of non-viral nucleic acid delivery vehicles have been prepared and studied for their transfection efficiencies. Recently, polymeric gene delivery vehicles have gained popularity for their low immunogenicity and high transfection efficiency. With the advent of controlled radical polymerization (CRP) and more specifically reversible addition-fragmentation chain transfer (RAFT) polymerization, it is now possible to develop well-defined polymers with predicted molecular weights and architectures. The work presented here focuses on the RAFT polymerization of a family of amphiphilic, cationic copolymers to be utilized for nucleic acid delivery. These copolymers are composed of a stabilizing hydrophilic block of oligo(ethylene glycol) methyl ether methacrylate (OEMGA) and a cationic, endosomolytic block of 2-(dimethylamino) ethyl methacrylate (DMAEMA), 2-(diethylamino) ethyl methacrylate (DEAEMA), or 2-(diisopropylamino) ethyl methacrylate (DPAEMA). The hydrophilic content of this copolymer series was kept constant while the degrees of polymerization of the cationic block of 25, 50, and 75 were targeted to elucidate the effects of tertiary amine functionalization on gene delivery efficacy. Means of characterization included gel permeation chromatography (GPC), dynamic light scattering (DLS), electrophoresis, and in vitro gene expression and toxicity studies. As a result from this study, our findings indicate the significance of cationic group functionalization on siRNA delivery, and the pH-responsive nucleic acid delivery vehicles synthesized show promise for future studies of nucleic acid delivery. |
