Grouping nanoparticles based on properties and transcriptomic response: are we dealing with a single nanoform or a set of nanoforms with common pulmonary hazards?

Abstract

The safety of titanium dioxide nanoparticles (TiO₂ NPs) has been a subject of debate for over two decades, primarily due to the lack of consensus on their toxicity. A comprehensive understanding of the molecular-level toxicity of TiO₂ NPs is essential for accurate safety evaluations and effective risk mitigation strategies. Thus, this study aims to elucidate the relationship between the physicochemical properties of TiO₂ NPs and their pulmonary toxicity at the molecular level. Additionally, it seeks to determine whether these properties and the corresponding transcriptomic responses can facilitate the categorization of TiO₂ nanoforms into groups with similar pulmonary hazards. Through the integration of bioinformatics and machine learning algorithms to analyze genome-wide transcriptomic profiles, we identified size, specific surface area, reactive oxygen species (ROS) production, crystalline structure, and surface modification as key determinants of TiO₂ NP toxicity at the transcriptomic level. Furthermore, we observed that different nanoforms of TiO₂ NPs, characterized by varying properties, can elicit distinct molecular-level responses, indicating that transcriptomic pathways are subject to different modes of perturbation. Our findings offer valuable insights into the safety considerations of TiO₂ NPs and lay the groundwork for future strategies to group nanoforms with similar patterns of hazards.