CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model

Alison M Wallbank; Alyssa E Vaughn; Steve Niemiec; Jill Bilodeaux; Tanner Lehmann; Lars Knudsen; Elayaraja Kolanthai; Sudipta Seal; Carlos Zgheib; Eva Nozik; Kenneth W Liechty; Bradford J Smith

doi:10.1016/j.nano.2023.102679

CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model

Nanomedicine. 2023 Jun:50:102679. doi: 10.1016/j.nano.2023.102679. Epub 2023 Apr 26.

Authors

Affiliations

¹ Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO, USA.
² Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
³ Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Centre for Lung Research (DZL), Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Germany.
⁴ Advanced Materials Processing and Analysis Center, Department of Materials Science and Engineering, University of Central Florida, Orlando, FL, USA.
⁵ Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, CO, USA; Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine and Banner Children's at Diamond Children's Medical Center, Tucson, AZ, USA.
⁶ Developmental Lung Biology, Cardiovascular Pulmonary Research Laboratories, Division of Pulmonary Sciences and Critical Care Medicine, Division of Pediatric Critical Care, Departments of Medicine and Pediatrics, University of Colorado, Aurora, CO, USA.
⁷ Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatric Pulmonary and Sleep Medicine, School of Medicine, University of Colorado, Aurora, CO, USA. Electronic address: bradford.smith@ucdenver.edu.

Abstract

Acute respiratory distress syndrome (ARDS) has high mortality (~40 %) and requires the lifesaving intervention of mechanical ventilation. A variety of systemic inflammatory insults can progress to ARDS, and the inflamed and injured lung is susceptible to ventilator-induced lung injury (VILI). Strategies to mitigate the inflammatory response while restoring pulmonary function are limited, thus we sought to determine if treatment with CNP-miR146a, a conjugate of novel free radical scavenging cerium oxide nanoparticles (CNP) to the anti-inflammatory microRNA (miR)-146a, would protect murine lungs from acute lung injury (ALI) induced with intratracheal endotoxin and subsequent VILI. Lung injury severity and treatment efficacy were evaluated via lung mechanical function, relative gene expression of inflammatory biomarkers, and lung morphometry (stereology). CNP-miR146a reduced the severity of ALI and slowed the progression of VILI, evidenced by improvements in inflammatory biomarkers, atelectasis, gas volumes in the parenchymal airspaces, and the stiffness of the pulmonary system.

Keywords: Bioactive nanoparticle therapeutic; Stereology; Sterile inflammatory model; Ventilator-induced lung injury.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Acute Lung Injury* / drug therapy
Acute Lung Injury* / genetics
Animals
Humans
Lung / metabolism
Mice
Respiratory Distress Syndrome* / metabolism
Ventilator-Induced Lung Injury* / drug therapy
Ventilator-Induced Lung Injury* / genetics
Ventilator-Induced Lung Injury* / metabolism

Substances

ceric oxide

Abstract

Publication types

MeSH terms

Substances

Grants and funding