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Amelioration of atherosclerotic inflammation and plaques via endothelial adrenoceptor-targeted eNOS gene delivery using redox-sensitive polymer bearing L-arginine

Title
Amelioration of atherosclerotic inflammation and plaques via endothelial adrenoceptor-targeted eNOS gene delivery using redox-sensitive polymer bearing L-arginine
Author
최재훈
Keywords
Redox-sensitive polymeric nanoparticles; L-arginine; Targeted delivery; Endothelial nitric oxide synthase; Inflammation; Atherosclerosis
Issue Date
2017-09
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v. 262, page. 72-86
Abstract
Endothelial dysfunction combined with inflammation leads to atherosclerosis. Endothelium-specific delivery of therapeutic agents at the cellular level-specifically in vivo-is still a difficult task for proper management of atherosclerosis. We designed a redox-sensitive poly(oligo-L-arginine) (rsPOLA) playing dual roles as an endothelium alpha-2 adrenoceptors(alpha-2ARs)-targeted gene carrier and as a substrate for endothelial nitric oxide synthase (eNOS). Overexpression of alpha-2ARs on atherosclerotic endothelial cells was confirmed and the eNOS/rsPOLA nanoplexes following systemic injection demonstrated to 1) enhance eNOS gene delivery into endothelial cells via alpha-2ARs/L-arginine specific binding, 2) increase intracellular level of nitric oxide, 3) suppress inflammatory response in endothelium and finally 4) reduce atherosclerotic plaque in a Ldlr(-/-) atherosclerotic mouse model. Among the tested nanoplexes [ eNOS/rsPOLA, eNOS/{poly(oligo-D-arginine), rsPODA} and eNOS/(racemic mixture, rsRM)], eNOS/rsPOLA reduced atherosclerotic inflammation most effectively as we hypothesized. Current treatment strategy provides strong potential for further development of a gene therapeutic system to ameliorate inflammation and progressive atherosclerotic plaques.
URI
https://www.sciencedirect.com/science/article/pii/S0168365917307289?via%3Dihubhttp://repository.hanyang.ac.kr/handle/20.500.11754/115453
ISSN
0168-3659; 1873-4995
DOI
10.1016/j.jconrel.2017.07.019
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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