Predicting Nanotoxicity across Materials Using Interpretable Machine Learning and Descriptors Based on the Periodic Table.

Journal: ACS applied materials & interfaces
Published Date: Dec 24, 2025

Abstract

The biological effects of engineered nanomaterials are largely determined by their intrinsic physicochemical properties; however, predicting these effects across materials with different core compositions remains a significant challenge. In this study, we developed an interpretable machine learning framework to enable cross-material nanotoxicity prediction using descriptors based on the periodic table. A curated data set comprising 1206 entries of metal oxide nanoparticles with cytotoxicity endpoints was constructed from high-quality literature sources. We evaluated multiple machine learning models to systematically analyze their performance using both within-material and cross-material validation strategies. Initial models based solely on experimental conditions and global nanomaterial properties showed high accuracy in within-material prediction but failed to generalize to unseen materials. To overcome this limitation, we introduced elemental-level descriptors, including electronegativity, ionization energy, atomic radius, and oxidation state. Incorporating these fundamental features significantly improved cross-material prediction performance, with coefficient of determination (R2) values from approximately 0.35 to 0.65 for unseen nanomaterials such as CuO, ZnO, MgO, and Cu2O. Further experimental validation using NiO and Cr2O3 nanoparticles on A549 and HUVEC cell lines confirmed the reliability of model predictions and highlighted material- and cell-type-specific toxic responses. Model interpretation and oxidative stress assay provided mechanistic insights into the cytotoxicity induced by the metal oxide nanoparticles. This study demonstrates the feasibility of cross-material toxicity prediction and establishes a scalable and interpretable computational framework for safer nanomaterial design and risk assessment.

Authors

  • Fang Liu
    The First Clinical Medical College of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China.
  • Jimin Zhu
    College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
  • Jing Zhang
    MOEMIL Laboratory, School of Optoelectronic Information, University of Electronic Science and Technology of China, Chengdu, China.
  • Peiqiang Mu
    Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, China.
  • Jikai Wen
    College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
  • Xu Wang
    Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907.
  • Yinbao Wu
    College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
  • Yan Wang
    College of Animal Science and Technology, Beijing University of Agriculture, Beijing, China.
  • Xiliang Yan
    Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay, Guangzhou University, Guangzhou, 510006, China. Electronic address: [email protected].
  • Bing Yan
    Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hosipital of Xiamen University, Xiamen, China.

Keywords

No keywords available for this article.

External Resources

Popular Topics
Recent Journals