Abstract
Titanium dioxide (TiO2) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO2 nanoparticles have been extensively studied, the toxicological characterization of TiO2 nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially available anatase TiO2 nanofibres using TiO2 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 TiO2 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 TiO2 NP did not decrease cell viability. TiO2 nanofibres were also found endowed with a marked haemolytic activity, at levels significantly higher than those observed with TiO2 nanoparticles or crocidolite. Moreover, TiO2 nanofibres and crocidolite, but not TiO2 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 TiO2 nanofibres, as well as by TiO2 nanoparticles and crocidolite. This study indicates that TiO2 nanofibres had significant toxic effects and, for most endpoints with the exception of pro-inflammatory changes, are more bio-active than TiO2 nanoparticles, showing the relevance of shape in determining the toxicity of nanomaterials. Given that several toxic effects of TiO2 nanofibres appear comparable to those observed with crocidolite, the possibility that they exert length dependent toxicity in vivo seems worthy of further investigation.
Highlights
High aspect ratio nanostructures (HARN), such as nanotubes, nanofibres, nanowires, are increasingly used in many industrial applications from electronics to photovoltaics
TiO2 nanofibres are increasingly used as photocatalytic components in solar cells, catalysts, cosmetic ingredients, preparing the ground for possible exposures, especially in occupational scenarios
In the present study we evaluated in vitro the biological effects of TiO2 nanofibres (NF) of industrial origin, investigating in different cell models their cytotoxic and pro-inflammatory effects as well as their capability to impair epithelial monolayers
Summary
High aspect ratio nanostructures (HARN), such as nanotubes, nanofibres, nanowires, are increasingly used in many industrial applications from electronics to photovoltaics. This association, based on morphology, is not an arbitrary link between very different materials but relies upon the structure-activity relationship that has been identified to promote fibre-type pathogenicity, as opposed to particle toxicity mediated by other mechanisms such as surface reactivity [1] or release of cytotoxic ions [2] This structure-activity relationship, known as the “fibre pathogenicity paradigm” (FPP), identifies three critical features that are required for a fibrous particle to present a fibre-type health hazard: aspect ratio and length (dimension/shape), persistence of a particle in the biological environment and its resistance to breakage and dissolution (durability) and, most crucially for consideration of risk, the exposure to the particle in question (dose) [3]. TiO2 nanofibres are increasingly used as photocatalytic components in solar cells (anode in dye-sensitized solar cells), catalysts, cosmetic ingredients, preparing the ground for possible exposures, especially in occupational scenarios
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