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논문번호 47
논문제목(영문) Suppression of post-angioplasty restenosis with an Akt1 siRNA-embedded coronary stent in a rabbit model.
국내외구분 국외 SCI여부 SCI(E)
연구책임자역할 공저자
주저자명 Che HL
교신저자명 Park IK
공동저자명 Che HL, Bae IH, Lim KS, Song IT, Lee H, Muthiah M, Namgung R, Kim WJ, Kim DG, Ahn Y, Jeong MH, Park IK.;
게제년월일 2012-07-21
ISSN 0142-9612
Impact Factor 8.557
학술지명 Biomaterials
서지사항 0집 / 33권 / 33호,   페이지(8548 - 8556)
요약초록문
(Abstract) 입력
Restenosis is the formation of blockages occurring at the site of angioplasty or stent placement. In order to avoid such blockages, the suppression of smooth muscle cells near the implanted stent is required. The Akt1 protein is known to be responsible for cellular proliferation, and specific inhibition of Akt1 gene expression results in the retardation of cell growth. To take advantage of these benefits, we developed a new delivery technique for Akt1 siRNA nanoparticles from a hyaluronic acid (HA)-coated stent surface. For this purpose, the disulfide cross-linked low molecular polyethyleneimine (PEI) (ssPEI) was used as a gene delivery carrier because disulfide bonds are stable in an oxidative extracellular environment but degrade rapidly in reductive intracellular environments. In this study, Akt1 siRNA showed efficient ionic interaction with the ssPEI carrier, which was confirmed by polyacrylamide gel electrophoresis. Akt1 siRNA/ssPEI nanoparticles (ASNs) were immobilized on the HA-coated stent surface and exhibited stable binding and localization, followed by time-dependent sustained release for intracellular uptake. Cellular viability on the nanoparticle-immobilized surface was assessed using A10 vascular smooth muscle cells, and the results revealed that immobilized ASNs exhibited negligible cytotoxicity against the adhering A10 cells. Transfection efficiency was quantified using a luciferase assay; the transgene expression of Akt1 suppression through the delivered Akt1 siRNA was measured using RT-PCR and western blot, demonstrating higher gene silencing efficiency when compared to other carriers. ASN coated on HA stents were deployed in the balloon-injured external iliac artery in rabbits in vivo. It was shown that the Akt1 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis in the post-implantation phase.
파일  B47. Biomaterials. 2012;33(33)8548-8556..pdf (1.5M) DATE : 2016-03-13 09:36:58