Albumin-Based Nanoparticles Loaded with miR-503 Antagonist Facilitate Neovascularization in the Ischemic Area of Myocardial Infarction

Abstract

Albumin is successfully applied as a nanocarrier in the clinical nanomedicine and the abnormal miR-503 expression is related to the development of myocardial infarction (MI). This study aimed to explore the efficacy of albumin nanoparticles (NPs)-based delivery of miR-503 antagonist for MI therapy. After establishment of an animal model of MI, mice were administered albumin NPs loaded with miR-503 agonist or antagonist, normal saline (model group), CCNE1 agonist, or CCNE1 inhibitor (n = 10) with 10 mice sham-operated. Murine peripheral blood was collected to measure endothelial progenitor cells (EPCs) in peripheral blood along with analysis of miR-503, CCNE1 and SDF-1α expression by RT-qPCR, formation of new blood vessels and EPCs viability. Albumin NPs loaded with miR-503 antagonist increased EPCs number and new blood vessels formation, accompanied with down-regulation of miR-503 and up-regulation of SDF-1α and CCNE1. The NPs carrying miR-503 agonist exerted an opposite activity with less EPCs and new blood vessels than sham-operated group without significant difference between agonist group and model group. Besides, miR-503 antagonist promoted EPCs viability. Furthermore, inhibition of CCNE1 suppressed blood vessel formation and miR-503 targeted CCNE1. In conclusion, albumin-based NPs loaded with miR-503 antagonist decrease miR-503 expression and increase CCNE1 and SDF-1α expression to promotes EPCs viability and enhance the formation of new blood vessels, thereby improving MI.