Titanium dioxide nanoparticles: metabolic profiling on human keratinocytes

Titanium dioxide particles (TiO2-NP) are classified as biologically inert and therefore they have been extensively used as excipient in pharmaceutical products and cosmetics. Human exposure may occur through ingestion and dermal penetration, or through inhalation route, during both the manufacturing process and use. In spite of the extensively use of TiO2-NP, the biological effects and the cellular response mechanisms are still not completely elucidated and thus a deeply understanding of the toxicological profile of this compound is required. Therefore, the major aim of this study has been the investigation on the early pathological, metabolic and toxicological processes induced by TiO2-NP by metabolomic that make possible the analysis of the whole cell response to nanomaterials. Our data show that although TiO2 does not affect cell cycle phase distribution, nor cell death, and these nanoparticles have a considerable and rapid effect on mitochondrial function. Metabolic analysis was performed on human keratinocyte cells to identify altered biochemical metabolites, many of which associated with the cellular stress response. The uptake of NP into the cultured cells was restricted to phagosomes and no other morphological changes were detected consistent with a specific role of mitochondria in this response. Since our study has shown significant and potentially pathogenic metabolic changes, it is evident that in vivo studies are required for a comprehensive description of the risk assessment and management related to TiO2. [1] Grande and Tucci. Mini-Reviews in Medicinal Chemistry. 2016; 16(9):762-9. [2] Tucci et al. Cell Death and Disease. 2013; 4:e549