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Facial amphipathic deoxycholic acid-modified polyethyleneimine for efficient MMP-2 siRNA delivery in vascular smooth muscle cells.

Authors
 Dongkyu Kim ; Dokyoung Lee ; Sun Hwa Kim ; Ji Hoon Jeong ; Donghoon Choi ; Su Young Chae ; Yeon Lim Jang 
Citation
 European Journal of Pharmaceutics and Biopharmaceutics, Vol.81(1) : 14~23, 2012 
Journal Title
 European Journal of Pharmaceutics and Biopharmaceutics 
ISSN
 0939-6411 
Issue Date
2012
Abstract
Clinical applications of RNA interference-based therapeutics such as small interfering RNAs (siRNAs) have been limited mainly due to low intracellular delivery efficiency in vitro and in vivo. In this study, facially amphipathic deoxycholic acid (DA)-modified polyethyleneimine (PEI(1.8)) (DA-PEI(1.8)) was synthesized and used as a potent carrier system for siRNA targeted against matrix metalloproteinase-2 (MMP-2) to inhibit the migration of vascular smooth muscle cells (SMCs), which is the major pathomechanism in the development of atherosclerosis and restenosis after arterial injury. A representative facial amphipathic bile acid DA having a high membrane permeability was conjugated to the terminal amine groups of the low molecular weight PEI(1.8) via amide bonds. The DA-PEI(1.8) conjugates formed self-assembled nanoparticles with siRNA molecules in an aqueous phase and the DA-PEI(1.8)/siRNA polyplexes became stabilized and condensed as particle incubation time increased from 0 to 4h. Both cellular internalization and target gene silencing were enhanced as the DA-PEI(1.8)/siRNA polyplexes stabilized. When vascular SMCs were transfected with MMP-2 siRNA, the DA-PEI(1.8)/siRNA polyplex formulation led to a significant decrease in MMP-2 gene expression, resulting in the suppression of cell migration. These results suggest that the DA-PEI(1.8)/MMP-2 siRNA delivery system may be useful in anti-restenotic treatment for various vasculoproliferative disorders such as atherosclerosis, in-stent restenosis, and vein graft failure.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/90223
DOI
10.1016/j.ejpb.2012.01.013
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0939641112000148
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