Molybdenum Disulfide Quantum Dots Attenuates Endothelial-to-Mesenchymal Transition by Activating TFEB-Mediated Lysosomal Biogenesis.

A defective lysosome-autophagy degradation pathway contributes to a variety of endothelial-to-mesenchymal transition (EndMT)-related cardiovascular diseases. Molybdenum disulfide quantum dots (MoS 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 MoS QDs with an average diameter of about 3.4 nm were synthesized by using a sulfuric acid-assisted ultrasonic method. The as-prepared MoS 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 MoS 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 MoS 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 MoS QDs against EndMT. Taken together, these results gain novel insights into the mechanisms by which MoS QDs regulate EndMT and facilitate the development of MoS-based nanoagents for the treatment of EndMT-related cardiovascular diseases.