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  1. NTU Scholars
  2. 醫學院
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Please use this identifier to cite or link to this item: https://scholars.lib.ntu.edu.tw/handle/123456789/592636
Title: Targeted polyelectrolyte complex micelles treat vascular complications in vivo
Authors: 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
Yang, Kai-Chien
Tirrell, Matthew V
Fang, Yun
Keywords: atherosclerosis; nanomedicine; nanoparticle; stenosis; vascular remodeling;Atherosclerosis; Nanomedicine; Nanoparticle; Stenosis; Vascular remodeling
Issue Date: 14-Dec-2021
Publisher: NATL ACAD SCIENCES
Journal Volume: 118
Journal Issue: 50
Start page/Pages: e2114842118
Source: Proceedings of the National Academy of Sciences of the United States of America
Abstract: 
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
metadata.dc.subject.other: 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
[SDGs]SDG3
Appears in Collections:醫學系

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