Spermine-alt-poly(ethylene glycol) polyspermine as a safe and efficient aerosol gene carrier for lung cancer therapy.
The clinical success of gene therapy critically depends upon the safety and efficiency of delivery system used. Although polyethylenimine (PEI) has been commonly used as an efficient cationic polymeric gene carrier due to its high transfection efficiency, its cytotoxicity and nondegradability limit the polymer's therapeutic applications in clinical trials. In this study, biocompatible polyspermine based on spermine (SPE) and poly(ethylene glycol) (PEG) diacrylate (SPE-alt-PEG) was synthesized using a Michael-type addition reaction, and its ability as an alternative gene carrier for lung cancer therapy was evaluated. SPE-alt-PEG polyspermine was complexed with plasmid DNA, and the resulting complexes were characterized by particle size and surface charge by dynamic light scattering, complex formation and DNA protection ability by gel retardation, and complex shape by energy-filtering transmission electron microscopy. The SPE-alt-PEG copolymer showed low cytotoxicity, and SPE-alt-PEG/DNA complexes showed efficacious transfection efficiency compared with 25 kDa PEI (PEI 25K). Also SPE-alt-PEG/GFP complexes were efficiently transferred into the lungs after aerosol administration without toxicity, and delivery of Pdcd4 gene as a therapeutic gene with SPE-alt-PEG polyspermine greatly reduced tumor size as well as tumor numbers in K-ras(LA1) lung cancer model mice compared relative to the effect observed for PEI 25K. These results suggest that SPE-alt-PEG has potential as a gene carrier for lung cancer gene therapy.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
You-Kyoung
YK
Kim
Chong-Su
CS
Cho
Myung-Haing
MH
Cho
Hu-Lin
HL
Jiang
D000336:Aerosols; D000818:Animals; D001672:Biocompatible Materials; D004247:DNA / Q000737:chemistry; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*; D013096:Spermine / Q000737:chemistry*; D014162:Transfection
D000336:Aerosols; D001672:Biocompatible Materials; D013096:Spermine; D011092:Polyethylene Glycols; D004247:DNA
aerosol delivery; biocompatibility; gene therapy; lung cancer; polyspermine