Cerium oxide nanoparticle delivery of microRNA-146a for local treatment of acute lung injury
Stephen Niemiec, Sarah A. Hilton, Alison Wallbank, Mark Azeltine, Amanda E. Louiselle, Hanan Elajaili, Ayed Allawzi, Junwang Xu, Courtney Mattson, Lindel C. Dewberry, Junyi Hu, Sushant Singh, Tamil S. Sakthivel, Sudipta Sea, Eva Nozik‐Grayck, Bradford J. Smith, Carlos Zgheib, Kenneth W. Liechty
Abstract
Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant in-hospital mortality and is the leading cause of death in COVID-19 patients. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis contribute to poor ARDS outcomes. Nanoparticle technology with cerium oxide nanoparticles (CNP) offers a mechanism by which unstable therapeutics such as the anti-inflammatory microRNA-146a can be locally delivered to the injured lung without systemic uptake. In this study, we evaluated the potential of the radical scavenging CNP conjugated to microRNA-146a (termed CNP-miR146a) in preventing acute lung injury (ALI) following exposure to bleomycin. We have found that intratracheal delivery of CNP-miR146a increases pulmonary levels of miR146a without systemic increases, and prevents ALI by altering leukocyte recruitment, reducing inflammation and oxidative stress, and decreasing collagen deposition, ultimately improving pulmonary biomechanics.