Dispersible MoS2 Nanosheets Activated TGF-β/Smad Pathway and Perturbed the Metabolome of Human Dermal Fibroblasts

In postgraphene two-dimensional materials (2DMs), MoS2 has attracted increasing attention in the biomedical field due to its excellent physicochemical properties. However, the toxicity and biocompatibility evaluation of MoS2 is not fully addressed. Herein, chitosan functionalized MoS2 (CS-MoS2) nanosheets, which showed perfect dispersibility and stability performances, were synthesized and characterized. We found that CS-MoS2 nanosheets inhibited the viability of human dermal fibroblasts (HDFs) moderately while causing cell membrane instability, ROS generation, and DNA damage in a dosage-dependent manner. CS-MoS2 nanosheets did not induce significant changes in the cell morphologies, but they seemed to impair the cell division of HDFs. CS-MoS2 nanosheets (100 μg/mL) activated EGFR and induced reactive oxygen species, Smad, and IL-1, which in turn led to cell inflammation and apoptosis. Furthermore, HDFs showed cellular stress responses when they were exposed to low concentrations of CS-MoS2 nanosheets (25...