2. Academic Validation
  3. Adverse Outcome Pathway-Based Strategies to Mitigate Ag2Se Quantum Dot-Induced Neurotoxicity

Adverse Outcome Pathway-Based Strategies to Mitigate Ag2Se Quantum Dot-Induced Neurotoxicity

  • ACS Nano. 2025 Mar 25;19(11):11029-11048. doi: 10.1021/acsnano.4c16813.
Yongshuai Yao 1,  Zhihui Wang 1,  Xiaoquan Huang 1 2,  Tingting Wei 1 3,  Na Liu 1 4,  Lingyue Zou 1 5,  Yiru Niu 1,  Yuanyuan Hu 1,  Qing Fang 1,  Xiaoli Wang 1 6,  Dong Qiao 1 7,  Congcong Li 1,  Min Chen 1 8,  Shujing Guan 1,  Yuying Xue 1,  Tianshu Wu 1,  Ting Zhang 1,  Meng Tang 1
Affiliations

Affiliations

  • 1 Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, People's Republic of China.
  • 2 School of Public Health, Wannan medical college, Wuhu 241002, People's Republic of China.
  • 3 Department of Sport, Huainan Normal University, Huainan 232038, People's Republic of China.
  • 4 Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou 310006, People's Republic of China.
  • 5 School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing 210023, People's Republic of China.
  • 6 Taizhou Center for Disease Control and Prevention, Taizhou 318000, People's Republic of China.
  • 7 Gusu District Center for Disease Control and Prevention, Soochow 215000, People's Republic of China.
  • 8 Yancheng Kindergarten Teachers College, Yancheng 224005, People's Republic of China.
PMID: 40063898 DOI: 10.1021/acsnano.4c16813
Abstract

Silver selenide quantum dots (Ag2Se QDs) show great advantages in tumor imaging due to their excellent optical performance and good biocompatibility. However, the ultrasmall particle size of Ag2Se QDs allows them to cross the blood-brain barrier, thus potentially affecting the central nervous system. Therefore, risk assessment and response strategies for Ag2Se 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 Ag2Se 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 risk management of nanomaterials. Furthermore, this paper guides the use of natural small-molecule drugs as a strategy to mitigate nanomaterial-induced neurotoxicity.

Keywords

Ag2Se quantum dot; adverse outcome pathways; mitochondrial dysfunction; mitophagy; molecular docking; neuroinflammation; quercetin.

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