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 2 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 2 NPs prevents hydrogen peroxide (H 2 O 2 )-induced endothelial senescence by modulating autophagic process. Our results showed that pretreatment with MoS 2 NPs inhibited H 2 O 2 -induced endothelial senescence and improved endothelial functions. Exposure of H 2 O 2 increased p62 level and blocked the fusion of autophagosomes with lysosomes, indicating of impaired autophagic flux in senescent endothelial cells. However, MoS 2 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 2 NPs on endothelial cells against H 2 O 2 -induced senescence.Thus, these results suggested that MoS 2 NPs rescue endothelial cells from H 2 O 2 -induced senescence by improving autophagic flux, and provide valuable information for the rational design of MoS 2 -based nanomaterials for therapeutic use in senescence-related diseases.