Shape-Related Toxicity of Titanium Dioxide Nanofibres

Titanium dioxide (TiO(2)) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO(2) nanoparticles have been extensively studied, the toxicological characterization of TiO(2) nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially available anatase TiO(2) nanofibres using TiO(2) nanoparticles (NP) and crocidolite asbestos as non-fibrous or fibrous benchmark materials. The evaluated endpoints were cell viability, haemolysis, macrophage activation, trans-epithelial electrical resistance (an indicator of the epithelial barrier competence), ROS production and oxidative stress as well as the morphology of exposed cells. The results showed that TiO(2) nanofibres caused a cell-specific, dose-dependent decrease of cell viability, with larger effects on alveolar epithelial cells than on macrophages. The observed effects were comparable to those of crocidolite, while TiO(2) NP did not decrease cell viability. TiO(2) nanofibres were also found endowed with a marked haemolytic activity, at levels significantly higher than those observed with TiO(2) nanoparticles or crocidolite. Moreover, TiO(2) nanofibres and crocidolite, but not TiO(2) nanoparticles, caused a significant decrease of the trans-epithelial electrical resistance of airway cell monolayers. SEM images demonstrated that the interaction with nanofibres and crocidolite caused cell shape perturbation with the longest fibres incompletely or not phagocytosed. The expression of several pro-inflammatory markers, such as NO production and the induction of Nos2 and Ptgs2, was significantly increased by TiO(2) nanofibres, as well as by TiO(2) nanoparticles and crocidolite. This study indicates that TiO(2) nanofibres had significant toxic effects and, for most endpoints with the exception of pro-inflammatory changes, are more bio-active than TiO(2) nanoparticles, showing the relevance of shape in determining the toxicity of nanomaterials. Given that several toxic effects of TiO(2) nanofibres appear comparable to those observed with crocidolite, the possibility that they exert length dependent toxicity in vivo seems worthy of further investigation.