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Poly(beta-amino ester) as a carrier for si/shRNA delivery in lung cancer cells

Cited 85 time in Web of Science Cited 85 time in Scopus
Authors
Jere, Dhananjay; Xu, Cheng-Xiong; Arote, Rohidas; Yun, Cheol-Heui; Cho, Myung-Haing; Cho, Chong-Su
Issue Date
2008-06
Citation
Biomaterials, Vol.29 No.16, pp.2535-2547
Keywords
non-viral vectorpoly(amino ester)siRNA deliverygene silencingAkt proteinlung cancer
Abstract
Efficient delivery of small interfering RNA (siRNA) or small hairpin RNA (shRNA) is a critical concern in RNA interference (RNAi) studies. In the present study, we evaluated biodegradable poly(beta-amino ester) (PAE) carrier composed of low molecular weight polyethylenimine and poly(ethylene glycol) for si/shRNA delivery in lung cancer cells. PAE carrier successfully delivered EGFP (enhanced green fluorescence protein) siRNA (siGFP) and silenced EGFP expression. The silencing achieved with PAE carrier was found to be nearly 1.5 times superior and safer than standard PEI25K. Also, our PAE carrier exhibited superior Akt1 shRNA delivery (shAkt) and thereby silenced oncoprotein Akt1 efficiently. PAE-shAkt mediated Akt1 knock-down hindered cancer cell growth in Akt1 specific manner. Superior shAkt delivery and low cytotoxicity of PAE carrier promoted Akt1 knock-down specific apoptosis, while low delivery efficiency and high cytotoxicity of PEI25K carrier mainly exhibited undesirable necrosis. Moreover, basic cancer properties like cell proliferation, malignancy and metastasis were reduced more efficiently using PAE-shAkt system. These findings demonstrated the potential of PAE as an alternative to PEI25K in si/shRNA-based RNAi studies. (c) 2008 Elsevier Ltd. All rights reserved.
ISSN
0142-9612
URI
https://hdl.handle.net/10371/172331
DOI
https://doi.org/10.1016/j.biomaterials.2008.02.018
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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