<p>Mitochondria-Modulating Porous Se@SiO<sub>2</sub> Nanoparticles Provide Resistance to Oxidative Injury in Airway Epithelial Cells: Implications for Acute Lung Injury</p>
Muyun Wang, Kun Wang, Guoying Deng, Xijian Liu, Xiaodong Wu, Haiyang Hu, Yanbei Zhang, Wei Gao, Qiang Li
Abstract
Background: Mitochondrial dysfunction played a vital role in the pathogenesis of various diseases, including acute lung injury (ALI). However, few strategies targeting mitochondria were developed in treating ALI. Recently, we fabricated a porous [email protected] 2 nanoparticles (NPs) with antioxidant properties. Methods: The protective effect of [email protected] 2 NPs was assessed using confocal imaging, immunoblotting, RNA-seq, mitochondrial respiratory chain (MRC) activity assay, and transmission electron microscopy (TEM) in airway epithelial cell line (Beas-2B). The in vivo efficacy of [email protected] 2 NPs was evaluated in a lipopolysaccharide (LPS)-induced ALI mouse model. Results: This study demonstrated that [email protected] 2 NPs significantly increased the resistance of airway epithelial cells under oxidative injury and shifted lipopolysaccharide-induced gene expression profile closer to the untreated controls. The cytoprotection of [email protected] 2 was found to be achieved by maintaining mitochondrial function, activity, and dynamics. In an animal model of ALI, pretreated with the NPs improved mitochondrial dysfunction, thus reducing inflammatory responses and diffuse damage in lung tissues. Additionally, RNA-seq analysis provided evidence for the broad modulatory activity of our [email protected] 2 NPs in various metabolic disorders and inflammatory diseases. Conclusion: This study brought new insights into mitochondria-targeting bioactive NPs, with application potential in curing ALI or other human mitochondria-related disorders. Keywords: mitochondrial dysfunction, porous [email protected] 2 nanoparticles, acute lung injury, anti-oxidative injury, anti-inflammation