Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing.

Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds.