Targeted polyelectrolyte complex micelles treat vascular complications in vivo

• DOI: 10.1073/pnas.2114842118
• Publication Date: 2021-12-08T20:20:41Z
• Authors: Zhengjie Zhou; Chih-Fan Yeh; Michael Mellas; Myung-Jin Oh; Jiayu Zhu; Jin Li; Ru-Ting Huang; Devin L. Harrison; Tzu-Pin Shentu; David Wu; Michael Lueckheide; Lauryn Carver; Eun Ji Chung; Lorraine Leon; Kai-Chien Yang; Matthew V. Tirrell; Yun Fang
• Keywords: Inflammation; Male; 0301 basic medicine; Mice, Knockout, ApoE; Endothelial Cells; Vascular Cell Adhesion Molecule-1; Mice, Transgenic; Biological Sciences; Network Pharmacology; Atherosclerosis; Polyelectrolytes; Up-Regulation; 3. Good health; Mice; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Animals; Humans; Micelles; Fluorescent Dyes

Significance Vascular disease is a leading cause of human morbidity and mortality and current therapies mainly target systemic risk factors but not the diseased vasculature per se. We have devised a targeted nanomedicine approach engineering self-assembled polyelectrolyte complex micelles that target inflamed vascular endothelium and simultaneously encapsulate therapeutic nucleic acids. We showed that this targeted nanomedicine strategy effectively delivers therapeutic nucleotides to inflamed endothelium in vivo. The causal role of increased endothelial miR-92a in driving atherosclerosis is established by a new transgenic mouse line. We demonstrated that targeted polyelectrolyte complex micelles significantly enhance the anti–miR-92a therapy treating vascular complications in vivo.