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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  ;  Yeon Lim Jang  ;  Su Young Chae  ;  Donghoon Choi  ;  Ji Hoon Jeong  ;  Sun Hwa Kim 
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
MeSH
Cell Movement ; Deoxycholic Acid/chemistry* ; Gene Expression Regulation ; Gene Silencing ; Humans ; Matrix Metalloproteinase 2/genetics* ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/metabolism ; Myocytes, Smooth Muscle/metabolism ; Nanoparticles ; Polyethyleneimine/chemistry* ; RNA Interference ; RNA, Small Interfering/administration & dosage* ; Time Factors ; Transfection
Keywords
Small interfering RNA ; Facial amphiphilicity ; Deoxycholic acid ; Matrix metallo proteinase-2 ; Smooth muscle cell migration ; Restenosis
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0939641112000148
DOI
22311297
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Kim, Dong Kyu(김동규)
Kim, Sun Hwa(김선화)
Lee, Do Kyoung(이도경)
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90223
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