Cellular and <i>In Vivo</i> Response to\nIndustrial, Food Grade, and Photocatalytic TiO<sub>2</sub> Nanoparticles

We encounter titanium\ndioxide nanoparticles (TiO<sub>2</sub> NPs)\nthroughout our daily lives in the form of food coloring, cosmetics,\nand industrial materials. They are used on a massive industrial scale,\nwith over 1 million metric tons in the global market. For the workers\nwho process these materials, inhalation is a major concern. The goal\nof our current research is to provide a direct comparison of the three\nmajor types of TiO<sub>2</sub> NPs (P25, E171, R101) in terms of surface\ncharacterization, cellular response, and <i>in vivo</i> response\nfollowing introduction into the lungs of mice. In both cellular and <i>in vivo</i> experiments, we observe a pro-inflammatory response\nto the P25 TiO<sub>2</sub> NPs that is not observed in the E171 or\nR101 TiO<sub>2</sub> NPs at mass-matched concentrations. Cellular\nexperiments measured a cytokine, TNF-α, as a marker of a pro-inflammatory\nresponse. <i>In vivo</i> experiments in mice measured the\nnumber of immune cells and four pro-inflammatory cytokines (IL-6,\nMIP-2, IP-10, and MCP-1) present in bronchoalveolar lavage fluid.\nA detailed physical and chemical characterization of the TiO<sub>2</sub> NPs shows that the P25 TiO<sub>2</sub> NPs are distinguished by\nsmaller primary particles suggesting that samples matched by mass\ncontain a larger number of P25 TiO<sub>2</sub> NPs. Cellular dose–response\nmeasurements with the P25, E171, and R101 TiO<sub>2</sub> NPs support\nthis hypothesis showing increased TNF-α release by macrophages\nas a function of TiO<sub>2</sub> NP dose. Overall, this direct comparison\nof the three major types of TiO<sub>2</sub> NPs shows that the number\nof particles in a dose, which is dependent on the particle diameter,\nis a key parameter in TiO<sub>2</sub> NP-induced inflammation.