Nano-titanium dioxide bioreactivity with human alveolar type-I-like epithelial cells: Investigating crystalline phase as a critical determinant

Abstract

There can be significant variability between bioreactivity studies of nanomaterials that are apparently the same, possibly reflecting differences in the models used and differing sources of experimental material. In this study, we have generated two crystal forms of titanium dioxide nanoparticles (nano-TiO₂), pure anatase and pure rutile to address the hypothesis that the bioreactivity of these nanoparticles with human alveolar epithelium will depend on their crystal phase. We used a human alveolar type-I-like epithelial cell model (TT1; generated in-house from primary human alveolar epithelial type II cells); these cells cover 95% of the alveolar epithelial surface area and are an important target cell for inhaled nanomaterials. Using literature as a guide, we hypothesised that pure anatase nano-TiO₂ would display greater bioreactivity with TT1 cells in comparison to pure rutile nano-TiO₂. However, we found the profile and pattern of inflammatory mediator release was similar between these two nano-TiO₂ formats, although pure rutile treatment caused a small, but consistently greater, response for IL-6, IL-8 and MCP-1. Interestingly, the temporal induction of oxidative stress (increased reactive oxygen species levels and depleted glutathione) varied markedly between the different nano-TiO₂ formats. We have shown that a combination of using nanomaterials synthesised specifically for toxicological study and the use of a highly relevant, reproducible human lung cell model, offers a useful approach to delineating the physicochemical properties of nanomaterials that may be important in their cellular reactivity.

• Alveolar type-I epithelium
• consumer products
• crystalline phase
• nanotoxicology
• titanium dioxide nanoparticles

Declaration of interest

Financial support for SS from Unilever, UK, is gratefully acknowledged. The research leading to these results has also received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 214478 (NanoReTox).

Supplementary material available online

Supplemental Figures S1 and S2