期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 15, 期 -, 页码 2287-2302出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S240301
关键词
mitochondrial dysfunction; porous Se@SiO2 nanoparticles; acute lung injury; anti-oxidative injury; anti-inflammation
资金
- National Natural Science Foundation of China [81870064]
- Gaoyuan project of Pudong Health and Family Planning Commission [PWYgy2018-06]
- Shanghai Jiao Tong University Medical and Engineering Cross Fund [YG2019QNA65]
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.
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