Cellular and In Vivo Response to Industrial, Food Grade, and Photocatalytic TiO₂ Nanoparticles

We encounter titanium dioxide nanoparticles (TiO₂ NPs) throughout our daily lives in the form of food coloring, cosmetics, and industrial materials. They are used on a massive industrial scale, with over 1 million metric tons in the global market. For the workers who process these materials, inhalation is a major concern. The goal of our current research is to provide a direct comparison of the three major types of TiO₂ NPs (P25, E171, R101) in terms of surface characterization, cellular response, and in vivo response following introduction into the lungs of mice. In both cellular and in vivo experiments, we observe a pro-inflammatory response to the P25 TiO₂ NPs that is not observed in the E171 or R101 TiO₂ NPs at mass-matched concentrations. Cellular experiments measured a cytokine, TNF-α, as a marker of a pro-inflammatory response. In vivo experiments in mice measured the number of immune cells and four pro-inflammatory cytokines (IL-6, MIP-2, IP-10, and MCP-1) present in bronchoalveolar lavage fluid. A detailed physical and chemical characterization of the TiO₂ NPs shows that the P25 TiO₂ NPs are distinguished by smaller primary particles suggesting that samples matched by mass contain a larger number of P25 TiO₂ NPs. Cellular dose-response measurements with the P25, E171, and R101 TiO₂ NPs support this hypothesis showing increased TNF-α release by macrophages as a function of TiO₂ NP dose. Overall, this direct comparison of the three major types of TiO₂ NPs shows that the number of particles in a dose, which is dependent on the particle diameter, is a key parameter in TiO₂ NP-induced inflammation.