4.6 Article

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

Journal

Publisher

ELSEVIER
DOI: 10.1016/j.nano.2021.102483

Keywords

Diabetic wounds; Cerium oxide nanoparticle (CNP); CNP-miR146a; Inflammation; Angiogenesis; Oxidative stress

Funding

  1. NIH [R01 DK118793 01A1]
  2. University of Colorado Denver and Children Hospital Colorado
  3. NSF [MRI XPS: ECCS: 1726636]

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Diabetic wounds are a significant healthcare burden due to impaired wound healing caused by oxidative stress and inflammation. The synthesized CNP-miR146a, which consists of cerium oxide nanoparticles (CNP) conjugated with microRNA-146a, has been shown to improve diabetic wound healing. This is achieved through the combined effects of CNP's free radical scavenger properties and miR146a's inhibition of the inflammatory pathway. The study investigates the mechanisms by which CNP-miR146a promotes diabetic wound healing, focusing on markers of inflammation, oxidative stress, fibrosis, and angiogenesis. The results demonstrate that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and reduces inflammation and oxidative stress, leading to faster closure of diabetic wounds.
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 NF kappa B 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. (c) 2021 Elsevier Inc. All rights reserved.

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