Silver nanoparticles reduce ACE2 expression via changing mitochondrial function in human fibroblast-like lung cell and periodontal ligament fibroblast cells

Abstract

Silver nanoparticles (AgNPs) have demonstrated antibacterial properties and are widely recognized as one of the most prominent types of nanoparticles. Recent studies have highlighted their effectiveness against coronaviruses. However, the detailed molecular mechanisms underlying the action of AgNPs on viruses and their impacts on the human body remain to be fully elucidated. Thus, we attempt to delineate the preventive effects of AgNPs against SARS-CoV-2 infection. Our findings indicate that treatment with AgNPs reduces ACE2 expression, a key receptor for SARS-CoV-2 particularly in normal oral and lung cells. Additionally, we observed a decrease in the binding affinity of the spike protein to the cell after AgNP treatment. Through western blot analysis, we identified the involvement of the AKT and/or mTOR signaling pathway in this process. Since AKT and mTOR signaling have been reported to affect mitochondrial function, we investigated the effects of AgNP treatment on mitochondria. As a result, we found the localization of AgNPs within mitochondria. Furthermore, it was accompanied by an increase in mitochondrial Fe²⁺ and reactive oxygen species levels, ultimately resulting in mitochondrial dysfunction. Our results underscore the remarkable efficacy of AgNP treatment in preventing coronavirus infections.