(31i) Polyelectrolyte Complex Micelles for Targeted Nucleotide Delivery to Treat Atherosclerosis

Atherosclerosis is the narrowing or hardening of arteries ascribed to the buildup of fatty plaque in the inner lining of arteries and remains the leading cause of morbidity and mortality in the United States and globally. Among all cells present in vasculature, vascular smooth muscle cells (VSMCs) are a major cell type that participate in all stages of atherosclerosis development as well as transdifferentiating into the majority of cells that make up atherosclerotic plaques. The purpose of this study is to achieve targeted delivery of therapeutic nucleotides to VSMCs to treat vascular complications. We engineered polyelectrolyte complex micelles (PCMs) displaying a VSMC-targeted peptide and encapsulating micro-RNA-145 (miR-145), which directs VSMC fate and regulates VSMC phenotypes. PCMs self-assemble through electrostatic interactions between positively charged Lysines in poly (ethylene glycol)-block-poly(L-lysine) and negatively charged miR-145. Therapeutic efficacies of the developed PCMs were tested both in vitro and in vivo, where the successful delivery of miR-145 was confirmed by increased miR-145 expression. In vivo studies showed that the rate of progressive increase in plaque area was significantly reduced, improving vasculature health. Confocal fluorescence imaging of arteries indicated successful targeting of PCMs towards VSMCs. These results collectively demonstrate that the engineered PCM is a promising candidate for cell-targeting nanomedicines to treat smooth muscle cell pathology and vascular complications.