Comparison of toxicity of different nanorod-type TiO₂ polymorphs in vivo and in vitro

It is predicted that the toxicity of nanoparticles may be different depending on the properties of the nanoparticles and biological system being tested. However, the factors that influence the toxicity of nanoparticles have not been adequately investigated. In this study, we characterized two types of TiO₂ nanorods, anatase (ATO) and brookite (BTO), and compared their toxicity in vivo and in vitro. ATO and BTO differed from each other most notably in their surface areas. Treatment with the two TiO₂ nanorods (10 μg ml^-1) produced similar effects on the cell cycle in eight cell lines which are derived from potential target organs of nanoparticles, with the BTO eliciting stronger responses than ATO in all cell lines, among the cell lines, H9C2 showed the maximal change. Similarly, when mice were exposed to two TiO₂ nanorods (1 mg kg^-1), BTO induced clearer histopathological lesions and triggered a more robust secretion of inflammatory cytokines than ATO. Furthermore, we compared the cellular response of both TiO₂ nanorods using BEAS-2B cells, the human bronchial epithelial cell line. Both nanorods induced cell death by increasing the formation of autophagosome-like vacuoles. The mitochondrial calcium concentration decreased by exposure of both types, but the distribution of lysosome and endoplasmic reticulum (ER) showed a clear difference between the two nanorods. Thus, we conclude that the surface area acts as an important factor which depends on toxicity of nanorod type-TiO₂ nanoparticles. Furthermore, the toxicity of nanoparticles varies according to the type of cells tested, and that the assembly of autophagosome-like vacuoles is a critical part of the cellular response to nanoparticle exposure.