Machine Learning-Driven Prediction of Reactive Oxygen Species Dynamics for Assessing Nanomaterials' Cytotoxicity

Nanomaterials (NMs) possess unique physicochemical features that set them apart from bulk counterparts. Their adjustable properties provide remarkable flexibility, giving rise to a wide array of variants. However, these attributes can also trigger complex biological interactions, particularly the generation of reactive oxygen species (ROS), which are central to nanomaterial-induced cytotoxicity. The ambivalent nature of ROS, essential for physiological signaling yet harmful when dysregulated, can lead to substantial health consequences. The scarcity of reliable toxicity and safety data, together with the inadequacies of conventional testing methods, highlights the urgent need for more effective strategies to assess nanomaterial-related hazards and risks. Given the intricate interplay between NMs and biological systems, computational approaches, particularly machine learning (ML), have emerged as powerful tools to model ROS dynamics, predict cytotoxic outcomes, and optimize nanomaterial design. This review highlights recent advances in applying ML to predict both the generation and neutralization of ROS by diverse NMs and to identify the critical determinants underlying ROS-mediated toxicity. These insights provide new opportunities for predictive nanotoxicology and the development of safer, application-tailored NMs.