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.

A defective lysosome-autophagy degradation pathway contributes to a variety of endothelial-to-mesenchymal transition (EndMT)-related cardiovascular diseases. Molybdenum disulfide quantum dots (MoS2 QDs) are nanoscale sizes in the planar dimensions and atomic structures of transition metal dichalcogenides (TMDs) materials with excellent physicochemical and biological properties, making them ideal for various biomedical applications. In this study, water-soluble MoS2 QDs with an average diameter of about 3.4 nm were synthesized by using a sulfuric acid-assisted ultrasonic method. The as-prepared MoS2 QDs exhibited low cytotoxicity of less than 100 μg/mL in both human umbilical vein endothelial cells and human coronary artery endothelial cells and showed novel biological properties to prevent EndMT and promote angiogenesis in vitro. We found that MoS2 QDs treatment-induced transcription factor (TFEB) mediated lysosomal biogenesis, which could cause autophagy activation. Importantly, using in vitro transforming growth factor (TGF)-β-induced EndMT model, we demonstrated that the cardiovascular protective effect of MoS2 QDs against EndMT acted through triggering TFEB nucleus translocation and restoring an impairment of autophagic flux, whereas genetic suppression of TFEB impaired the protective action of MoS2 QDs against EndMT. Taken together, these results gain novel insights into the mechanisms by which MoS2 QDs regulate EndMT and facilitate the development of MoS2-based nanoagents for the treatment of EndMT-related cardiovascular diseases.