Aerosol delivery of programmed cell death protein 4 using polysorbitol-based gene delivery system for lung cancer therapy

Abstract

The development of a safe and effective gene delivery system is the most challenging obstacle to the broad application of gene therapy in the clinic. In this study, we report the development of a polysorbitol-based gene delivery system as an alternative gene carrier for lung cancer therapy. The copolymer was prepared by a Michael addition reaction between sorbitol diacrylate (SD) and spermine (SPE); the SD–SPE copolymer effectively condenses with DNA on the nanoscale and protects it from nucleases. SD–SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo, and aerosol delivery of SD-SPE complexes with programmed cell death protein 4 DNA significantly suppressed lung tumorigenesis in K-ras^LA1 lung cancer model mice. These results demonstrate that SD–SPE has great potential as a gene delivery system based on its excellent biocompatibility and high gene delivery efficiency for lung cancer gene therapy.

• Accelerated transfection
• aerosol delivery
• gene therapy
• non-viral vector
• polysorbitol
• polyspermine