title: 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.
authors.affiliation: State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University , Nanjing , PR China .
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
authors.forename: Fengguo
authors.initials: F
authors.lastname: Xu
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000336:Aerosols / Q000737:chemistry*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016601:RNA-Binding Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D013012:Sorbitol / Q000737:chemistry; D013096:Spermine / Q000737:chemistry; D014162:Transfection / Q000379:methods
chemical_list: D000336:Aerosols; D051017:Apoptosis Regulatory Proteins; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; D013096:Spermine; D013012:Sorbitol
keywords: Accelerated transfection; aerosol delivery; gene therapy; non-viral vector; polysorbitol; polyspermine