Molybdenum Disulfide Nanoparticles Resist Oxidative Stress-Mediated Impairment of Autophagic Flux and Mitigate Endothelial Cell Senescence and Angiogenic Dysfunctions.

The impairment of autophagy involves oxidative stress-induced cellular senescence, leading to endothelial dysfunctions and the onset of cardiovascular diseases. As molybdenum disulfide nanoparticles (MoS NPs), representative transition metal dichacogenide materials, have great potential as a multifunctional therapeutic agent against various disorders, the present study aimed to investigate whether MoS NPs prevents hydrogen peroxide (HO)-induced endothelial senescence by modulating autophagic process. Our results showed that pretreatment with MoS NPs inhibited HO-induced endothelial senescence and improved endothelial functions. Exposure of HO increased p62 level and blocked the fusion of autophagosomes with lysosomes, indicating of impaired autophagic flux in senescent endothelial cells. However, MoS NPs pretreatment efficiently suppressed cellular senescence through triggering autophagy and resisting impaired autophagic flux. Furthermore, the genetic inhibition of autophagy by siRNA against Beclin 1 or ATG-5 directly abrogated the protective action of MoS NPs on endothelial cells against HO-induced senescence.Thus, these results suggested that MoS NPs rescue endothelial cells from HO-induced senescence by improving autophagic flux, and provide valuable information for the rational design of MoS-based nanomaterials for therapeutic use in senescence-related diseases.