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 (MoS2 NPs), representative transition metal dichacogenide materials, have great potential as a multifunctional therapeutic agent against various disorders, the present study aimed to investigate whether MoS2 NPs prevents hydrogen peroxide (H2O2) induced endothelial senescence by modulating autophagic process. Our results showed that pretreatment with MoS2 NPs inhibited H2O2-induced endothelial senescence and improved endothelial functions. Exposure of H2O2 increased p62 level and blocked the fusion of autophagosomes with lysosomes, indicating of impaired autophagic flux in senescent endothelial cells. However, MoS2 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 MoS2 NPs on endothelial cells against H2O2-induced senescence.Thus, these results suggested that MoS2 NPs rescue endothelial cells from H2O2-induced senescence by improving autophagic flux, and provide valuable information for the rational design of MoS2-based nanomaterials for therapeutic use in senescence-related diseases.