Machine Learning Framework for Multi-Endpoint Quantum Dot Toxicity Prediction with Organoid Validation and Drug Target Discovery

Quantum dots (QDs) possess unique optical and electronic properties, enabling wide applications in biomedicine and optoelectronics, but their nanoscale size and surface chemistry could pose potential toxicity risks. This study established a systematic, multi-endpoint framework for QD toxicity assessment. Physicochemical properties of various QDs and their multiple toxicity endpoints, including cell death, inflammation, and oxidative stress, were collected to build machine learning models (RF, XGBoost, KNN, SVM). The predictive toxic effects were then validated based on the brain organoid. Shapley Additive exPlanations (SHAP) analysis revealed that exposure dose and particle size were key cross-model drivers, while zeta potential and optical properties differentially affected specific toxicity endpoints. Integration of GEO-derived differentially expressed genes with protein-protein interaction networks and molecular docking showed that the proteasome inhibitor Carfilzomib is an efficient interventive drug because of its strongest binding to core targets. In this study, the framework of prediction, validation and intervention effectively evaluated multi-endpoint QD toxicity and provided a systematic approach for safety assessments and strategy developments of nanomaterials.