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 Se@SiO₂ nanoparticles (NPs) with antioxidant properties.
Methods: The protective effect of Se@SiO₂ 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 Se@SiO₂ NPs was evaluated in a lipopolysaccharide (LPS)-induced ALI mouse model.
Results: This study demonstrated that Se@SiO₂ 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 Se@SiO₂ 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 Se@SiO₂ 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 Se@SiO₂ nanoparticles, acute lung injury, anti-oxidative injury, anti-inflammation