主催: 日本毒性学会
Polyethylenimine (PEI) has been widely used as a cationic polymeric gene carrier because of high transfection efficiency. However, the use of PEI has been hindered at the practical application because of its cytotoxicity. In this study, we research the development of poly(amino ester) (PAE) based on glycerol propoxylate triacrylate (GPT) and spermine (SPE) as an alternative gene carrier for lung cancer therapy. GPT-SPE copolymer was synthesized by Michael addition reaction between GPT and SPE, and the efficacy was evaluated using shAkt1 as a model therapeutic gene. The molecular weight and composition were characterized using gel permeability chromatography (GPC) and (1)H-nuclear magnetic resonance ((1)H-NMR), respectively. The GPT-SPE could condense DNA with approximately 163nm size and protect the DNA from nucleases. GPT-SPE/DNA complexes showed high transfection efficiency with low toxicity both in vitro and in vivo. Furthermore, aerosol delivery of GPT-SPE/Akt1 shRNA complexes significantly suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice. These results suggest that GPT-SPE may be applied for shRNA-based lung cancer gene therapy.
