期刊
BIOMATERIALS
卷 35, 期 26, 页码 7562-7573出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.05.025
关键词
siRNA delivery; Myocardial ischemia-reperfusion injury; RAGE siRNA; Deoxycholic acid-modified; polyethylenimine
资金
- Global Innovative Research Center (GiRC) [2012K1A1A2A01056095]
- program of National Research Foundation of Korea (NRF)
- Intramural Research Program of KIST
- National Research Foundation of Korea [2012K1A1A2A01056095] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Inflammatory response in myocardial ischemia-reperfusion injury plays a critical role in ventricular remodeling. To avoid deleterious effects of overwhelming inflammation, we blocked the expression of receptor for advanced glycation end-products (RAGE), a key mediator of the local and systemic inflammatory responses, via RNAi mechanism. Herein, a facial amphipathic deoxycholic acid-modified low molecular weight polyethylenimine (DA-PEI) was used as a siRNA delivery carrier to myocardium. The DA-PEI conjugate formed a stable complex with siRNA via electrostatic and hydrophobic interactions. The siRAGE/DA-PEI formulation having negligible toxicity could enhance intracellular delivery efficiency and successfully suppress RAGE expression both in vitro and in vivo. Furthermore, the cardiac administration of siRAGE/DA-PEI reduced apoptosis and inflammatory cytokine release, subsequently led to attenuation of left ventricular remodeling in rat myocardial infarction model. The potential therapeutic effects of RAGE gene silencing on myocardial ischemia-reperfusion injury may suggest that the siRAGE/DA-PEI delivery system can be considered as a promising strategy for treating myocardial infarction. (C) 2014 Elsevier Ltd. All rights reserved.
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