气候变化领域集成服务门户(CCPortal): Targeted polyelectrolyte complex micelles treat vascular complications in vivo

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DOI	10.1073/pnas.2114842118
	Targeted polyelectrolyte complex micelles treat vascular complications in vivo
	Zhou Z.; Yeh C.-F.; Mellas M.; Oh M.-J.; Zhu J.; Li J.; Huang R.-T.; Harrison D.L.; Shentu T.-P.; Wu D.; Lueckheide M.; Carver L.; Chung E.J.; Leon L.; Yang K.-C.; Tirrell M.V.; Fang Y.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:50
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Atherosclerosis; Nanomedicine; Nanoparticle; Stenosis; Vascular remodeling
语种	英语
scopus关键词	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
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250936
作者单位	Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States; Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637, United States; Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taipei, 100, Taiwan; Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637, United States; Materials Science Division, Argonne National Laboratory, Lemont, IL 60439, United States
推荐引用方式 GB/T 7714	Zhou Z.,Yeh C.-F.,Mellas M.,et al. Targeted polyelectrolyte complex micelles treat vascular complications in vivo[J],2021,118(50).
APA	Zhou Z..,Yeh C.-F..,Mellas M..,Oh M.-J..,Zhu J..,...&Fang Y..(2021).Targeted polyelectrolyte complex micelles treat vascular complications in vivo.Proceedings of the National Academy of Sciences of the United States of America,118(50).
MLA	Zhou Z.,et al."Targeted polyelectrolyte complex micelles treat vascular complications in vivo".Proceedings of the National Academy of Sciences of the United States of America 118.50(2021).