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Suppression of lung cancer progression by biocompatible glycerol triacrylate-spermine-mediated delivery of shAkt1

Cited 30 time in Web of Science Cited 31 time in Scopus
Authors
Hong, Seong-Ho; Kim, Ji-Eun; Kim, You-Kyoung; Minai-Tehrani, Arash; Shin, Ji-Young; Kang, Bitna; Kim, Hye-Joon; Cho, Chong-Su; Chae, Chanhee; Jiang, Hu-Lin; Cho, Myung-Haing
Issue Date
2012-02
Citation
International journal of nanomedicine, Vol.7, pp.2293-2306
Keywords
lung cancergene therapyaerosol deliveryspermine
Abstract
Background: Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate-spermine (GT-SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy. Methods: The GT-SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance. Results: The GT-SPE successfully protected the DNA from nucleases. The average particle size of the GT-SPE was 121 nm with a zeta potential of +23.45 mV. The GT-SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT-SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-ras(LA1) lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT-SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively. Conclusion: Our data suggest that GT-SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy.
ISSN
1176-9114
URI
https://hdl.handle.net/10371/172394
DOI
https://doi.org/10.2147/IJN.S29152
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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