Adverse Outcome Pathway-Based Strategies to Mitigate Ag 2 Se Quantum Dot-Induced Neurotoxicity

作者：Yongshuai Yao, Zhihui Wang, Xiaoquan Huang, Tingting Wei, Na Liu, Lingyue Zou, Yiru Niu, Yu Lin Hu, Qing Fang, Xiaoli Wang, Dong Qiao, Congcong Li, Min Chen, Shujing Guan, Yuying Xue, Tianshu Wu, Ting Zhang, Meng Tang · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.4c16813 · 被引用次数：16 · 研究领域：Quantum Dots Synthesis And Properties、Graphene and Nanomaterials Applications、Carbon and Quantum Dots Applications

Silver selenide quantum dots (Ag 2 Se QDs) show great advantages in tumor imaging due to their excellent optical performance and good biocompatibility. However, the ultrasmall particle size of Ag 2 Se QDs allows them to cross the blood–brain barrier, thus potentially affecting the central nervous system. Therefore, risk assessment and response strategies for Ag 2 Se QDs are important. The adverse outcome pathway (AOP) framework makes it possible to develop risk management strategies based on toxicity mechanisms. In this study, using the AOP framework, we constructed causal mechanism relationship diagrams at different biological levels of Ag 2 Se QD neurotoxicity. In this framework, excess mitochondrial reactive oxygen species (mtROS) triggered Nod-like receptor protein 3 (NLRP3) inflammasome activation in microglia was molecular initiation event (MIE). Proinflammatory mediator secretion and microglia activation were key events (KEs) at the cellular level. Neuroinflammation and neuronal damage were KEs at the organ/tissue level. Altered hippocampal physiology was the adverse outcome (AO) at the individual level. Based on the established AOP framework, further studies confirmed that mtROS-activated nuclear-factor-E2-related factor 2 (Nrf2)/PTEN-induced kinase 1 (PINK1)- mitophagy contributed to weaken the MIE. Molecular docking-assisted molecular biology experiments demonstrated that quercetin (Qu) enhanced this process. This article emphasizes the importance of the AOP in the ...