Engineered titanium dioxide nanowire toxicity in vitro and in vivo.
Porter-DW; Holian-A; Sriram-K; Wu-N; Wolfarth-M; Hamilton-R; Buford-M
Toxicologist 2008 Mar; 102(1):306
While the application and benefits of manufacturing nanowires is highly promising, their adverse effects have not been fully investigated. For these studies, TiO2 nanowires (anatase, diameter=80 nm, length=20-25 microm) were synthesized using sol-gel process directed by a porous anodic aluminum oxide template. We conducted in vitro studies using alveolar macrophages isolated from both C57Bl/6 and Balb/c mice assessing toxicity with 4 hr suspension incubations by trypan blue exclusion and apoptosis using Cell Death ELISA. TiO2 nanospheres caused no toxicity or apoptosis up to 200 microg/ml. In contrast, TiO2 nanowires caused significant and marked dose-dependent toxicity and increase in apoptosis. Furthermore, TiO2 nanowires, but not nanospheres increased alveolar macrophage antigen presenting activity (using ovalbumin and T cells from DO11.10 mice) to similar extents as the potent particle crystalline silica. For in vivo studies we exposed C57Bl/6 mice by pharyngeal aspiration to TiO2 nanowires (0-80 microg/mouse) and examined lung and brain responses at one day post-exposure. In the lung, exposure to TiO2 nanowires induced dose-dependent increases in the expression of the inflammatory mediators TNF-alpha (1.8- to 5-fold), MIP-2 (4- to 33-fold) and CCL2 (7- to 30-fold). In the brain, pulmonary exposure to TiO2 nanowires induced expression of the endothelial cell adhesion molecule E-selectin in olfactory bulb (4-6 fold), suggestive of altered blood brain barrier (BBB) permeability. Unlike the dose-dependent pulmonary effects, the neural responses were elicited only by higher doses of the nanowires. Whether the BBB changes observed are a consequence of the translocation of these nanoparticles to the brain or a systemic inflammatory response remains to be investigated. Taken together, the data suggest that exposure to TiO2 nanowires may result in adverse health outcomes.
Particulates; Particulate-dust; Cell-biology; Biological-factors; Biological-monitoring; Biological-effects; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Pulmonary-system; Laboratory-animals; Brain-disorders; Brain-function; Breathing; Immune-system-disorders; Immunotoxins; Nanotechnology
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington