Abstract

Silver Selenide quantum dots (Ag 2 Se QDs) have great potential for biomedical applications due to their excellent optical properties, which has raised concerns about their health hazards. Previous studies have shown that exposure to Ag 2 Se QDs can induce neurotoxicity, but the underlying mechanisms have not been fully elucidated. In this study, Ag 2 Se QDs activated Nod-like receptor protein 3 (NLRP3) inflammasomes in microglia. Interestingly, we found that Ag 2 Se QDs-induced NLRP3 inflammasome activation was ferroptosis-dependent. Mechanistically, the overproduction of mitochondrial reactive oxygen species (mtROS) led to the leakage of mitochondrial DNA (mtDNA) into the cytoplasm via the open mitochondrial permeability transition pore (mPTP), thereby activating stimulator of interferon genes (STING)-dependent ferritinophagy. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy resulted in the degradation of ferritin heavy chain 1 (FTH1) and the release of iron ions, ultimately triggering ferroptosis. In order to assist in the risk assessment of Ag 2 Se QDs and the development of risk management strategies. Based on the above experimental data, we constructed an Adverse Outcome Pathway (AOP) framework for Ag 2 Se QDs neurotoxicity and emphasized the significance of alleviating mitochondrial damage in preventing neurotoxicity. Overall, the present study reveals new mechanisms of Ag 2 Se QDs-induced neurotoxicity. Meanwhile, this study provides insightful references for toxicity assessment and address. Graphical The alternative text for this image may have been generated using AI.