Mitochondria-Modulating Porous Se@SiO2 Nanoparticles Provide Resistance to Oxidative Injury in Airway Epithelial Cells: Implications for Acute Lung Injury

Abstract

Muyun Wang,1,* Kun Wang,1,* Guoying Deng,2,* Xijian Liu,3 Xiaodong Wu,1 Haiyang Hu,4 Yanbei Zhang,5 Wei Gao,1 Qiang Li1 1Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, People’s Republic of China; 2Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, People’s Republic of China; 3College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, People’s Republic of China; 4Department of Cardiothoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, People’s Republic of China; 5Department of Geriatric Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Anhui 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Gao; Qiang Li Email [email protected]; [email protected]: 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  

Keywords

• mitochondrial dysfunction
• porous se@sio2 nanoparticles
• acute lung injury
• anti-oxidative injury
• anti-inflammation