Regulation of Autophagy Orchestrates Pyroptotic Cell Death in Molybdenum Disulfide Quantum Dot-Induced Microglial...

Molybdenum disulfide quantum dots (MoS₂ QDs) represent an emerging class of two-dimensional (2D) atomically layered transition metal dichalcogenide nanostructures with few nanometers in lateral size, which show attractive potential as versatile platforms for theranostic applications in various neurological disorders. However, the potential impacts of MoS₂ QDs on microglia remain unclear. In this report, we showed that exposure of microglia to MoS₂ QDs triggered NLRP3 inflammasome activation as revealed by the cleavage of the inactive precursor of caspase-1 to its active form and the increased release of downstream pro-inflammatory cytokines, resulting in microglia cell death that occurred through caspase-1-dependent pyroptosis. We also found that MoS₂ QDs activated autophagy, and suppression of autophagy by specific inhibitors potentiated MoS₂ QD-induced pyroptosis. Additionally, MoS₂ QDs stimulated mitochondria-derived reactive oxygen species (mtROS) generation in BV-2 cells. However, ROS scavengers could diminish the MoS₂ QD-mediated NLRP3 inflammasome activation and pyroptotic cell death in microglia. Overall, our findings identified pyroptosis as a cellular response to MoS₂ QD exposure in microglial cells, affording novel insights into the neurotoxicity of MoS₂ QDs and facilitating the rational design and application of functional MoS₂ QDs in neuroscience.