https://scholars.lib.ntu.edu.tw/handle/123456789/592636
標題: | Targeted polyelectrolyte complex micelles treat vascular complications in vivo | 作者: | Zhou, Zhengjie CHIH-FAN YEH Mellas, Michael Oh, Myung-Jin Zhu, Jiayu Li, Jin Huang, Ru-Ting Harrison, Devin L Shentu, Tzu-Pin Wu, David Lueckheide, Michael Carver, Lauryn Chung, Eun Ji Leon, Lorraine KAI-CHIEN YANG Tirrell, Matthew V Fang, Yun |
關鍵字: | atherosclerosis; nanomedicine; nanoparticle; stenosis; vascular remodeling;Atherosclerosis; Nanomedicine; Nanoparticle; Stenosis; Vascular remodeling | 公開日期: | 14-十二月-2021 | 出版社: | NATL ACAD SCIENCES | 卷: | 118 | 期: | 50 | 起(迄)頁: | e2114842118 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92aEC-TG /Apoe-/- ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe-/- mice. We tested the therapeutic effectiveness of the VCAM-1-targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1-targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti-miR-92a therapy in treating atherosclerosis and stenosis in Apoe-/- mice is markedly enhanced by the VCAM-1-targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/592636 | ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.2114842118 | SDG/關鍵字: | fluorescent dye; microRNA; Mirn92 microRNA, mouse; polyelectrolyte; vascular cell adhesion molecule 1; animal; apolipoprotein E knockout mouse; atherosclerosis; endothelium cell; gene expression regulation; genetics; human; inflammation; male; metabolism; micelle; mouse; transgenic mouse; upregulation; Animals; Atherosclerosis; Endothelial Cells; Fluorescent Dyes; Gene Expression Regulation; Humans; Inflammation; Male; Mice; Mice, Knockout, ApoE; Mice, Transgenic; Micelles; MicroRNAs; Network Pharmacology; Polyelectrolytes; Up-Regulation; Vascular Cell Adhesion Molecule-1 |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。