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Polymeric Vector-Mediated Targeted Delivery of Anti-PAK1 siRNA to Macrophages for Efficient Atherosclerosis Treatment

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posted on 2019-08-23, 13:33 authored by Teng Wu, Hong Xiao, Liejing Lu, Yali Chen, Yong Wang, Wenhao Xia, Ming Long, Jun Tao, Jun Shen, Xintao Shuai
Atherogenesis, initially induced by endothelial structure alteration and dysfunction, is the main cause of cardiovascular diseases that jeopardize public health. Unfortunately, an efficient strategy for atherosclerosis treatment is still far from satisfying the clinical requirements. Dyslipidemia and chronic inflammatory responses, especially the overexpression of the pro-atherosclerotic factors monocyte chemotactic protein 1 (MCP-1) and interleukin-6 (IL-6) in plaques, represent the key features that promote the development of atherosclerosis. Here, a CD36 antibody-modified small-interfering RNA (siRNA) nanomedicine based on the mPEG-PAsp-(g-PEI) vector was developed for atherosclerosis therapy. In vitro and in vivo studies demonstrated that the synthesized siRNA nanomedicine targeted macrophages, reduced CD36 expression, and inhibited IL-6 and MCP-1 upregulation, and eventually reduced the formation of foam cells and alleviated the pathological process of atherosclerosis. These results indicate that the targeted delivery of anti-PAK1 siRNA using a CD36 antibody-modified polymeric vector represents a novel and efficient strategy for atherosclerosis treatment.

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