CYTOTOXICITY OF MICRO AND NANO METALLOOXIDE : A COMPARATIVE STUDY

Nanomaterials exhibit unique properties directly related to the size, composition and shape of the nanostructures. Whereas the potential benefits of nanotechnologies have been welcomed, concerns have been expressed that properties such as high surface reactivity and ability to cross cell membranes may result in greater toxicity. The present study has addressed the key question which physical and chemical characteristics of nanoparticles are mostly responsible for toxicity, in order to establish the possible existence of a general mode-of-action for nanosized particles. To this purpose different nano- and micro sized metal oxides with similar equivalent spherical diameter, were evaluated in alveolar macrophages and glial cells. Cell death and activation of the inflammatory response were observed after exposure to both Cr2O3 nano (28.4 nm) and Cr2O3 micro (50 μm), but in a different manner. Cr2O3 28.4 nm (25-100 μg/ml) induced a significant macrophages death and release of TNF-α after 24h treatment. Cell death only, occurred in glial cells and the effect was less pronounced than in macrophages (significant at 50 μg/ml, % of cell death in glia: 32+3.8%; in macrophages: 82.7+26.8%). On the contrary, Cr2O3 50 μm induced both a significant death and TNF-α release at 50-100 μg/ml, but only in glial cells. TNF-α was not involved in Cr2O3 induced cell death, since no protection was observed in the presence of a TNF-α neutralizing antibody. On the contrary, phagocytic activity seems to be relevant to counteract Cr2O3 28.4 nm toxicity. Pre-incubation with Jasplakinolide, a cytoskeleton stabilizer, greatly worsen Cr2O3 28.4 nm induced macrophages death. Cr2O3 was then compared to TiO2. TiO2 27.6 nm did not affect any of the cultures tested, while glial death was observed after TiO2 44 μm (25-100 mg/ml) treatment. Our results indicate that reduction to nanomolar dimension is not sufficient to determine the toxicological profile of a particle, but the “ingredient” of the particle and the characteristics of the cells are also relevant.