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Aerosol delivery of spermine-based poly(amino ester)/Akt1 shRNA complexes for lung cancer gene therapy

Cited 36 time in Web of Science Cited 40 time in Scopus
Authors
Jiang, Hu-Lin; Hong, Seong-Ho; Kim, You-Kyoung; Islam, Mohammad Ariful; Kim, Hye-Joon; Choi, Yun-Jaie; Nah, Jae-Woon; Lee, Kee-Ho; Han, Ki-Won; Chae, Chanhee; Cho, Chong-Su; Cho, Myung-Haing
Issue Date
2011-11
Citation
International Journal of Pharmaceutics, Vol.420 No.2, pp.256-265
Keywords
Lung cancerGene therapyPoly(amino ester)SpermineAerosol delivery
Abstract
Polyethylenimine (PEI) has been commonly used as a cationic polymeric gene carrier due to high transfection efficiency, however, its cytotoxicity has hindered the practical application. In this study, we report 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 prepared 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 H-1-nuclear magnetic resonance (H-1-NMR), respectively. The GPT-SPE could effectively condense DNA with about 163 nm size and protect the DNA from nucleases. GPT-SPE/DNA complexes showed excellent transfection 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 can be used in shRNA-based lung cancer gene therapy. (c) 2011 Elsevier B.V. All rights reserved.
ISSN
0378-5173
URI
https://hdl.handle.net/10371/172404
DOI
https://doi.org/10.1016/j.ijpharm.2011.08.045
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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