Effects of coating materials and size of titanium dioxide particles on their cytotoxicity and penetration into the cellular membrane

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In order to estimate the effects of the size and surface treatment (coating or non-coating) of titanium dioxide particles on their cytotoxicity and penetration into the cellular membrane, two types of non-treated titanium dioxide (TiO2) particles of 20 nm (LU175) and 250 nm (LU205) were exposed to CHO cells, RBL-2H3 cells, A431 cells, B16 melanoma, NHEK(F), and NHSF, and six types of surface-treated or non-treated TiO2 particles of 35 nm were exposed to RBL-2H3 cells and NHSF. The order of half-maximal inhibitory concentrations (IC50s) of LU175 was NHSF < CHO, RBL-2H3 < A431 < B16 melanoma, NHEK(F). On the other hand, LU205 showed no cytotoxicity against any cells. Surface-treated TiO2 showed much less cytotoxicity against RBL-2H3 cells than non-treated TiO2. Then, between 0.5 and 10 mg of LU175 or LU205 was exposed to CHO cells. After 24 hr, the amount of LU175 in cellular cytosol increased dose-dependently. On the other hand, the amount of LU205 in cellular cytosol was much less than that of LU175. The proportion of surface-treated TiO2 in the cellular cytosol of RBL-2H3 cells differed for each coating material. These results suggested that TiO2 has different cytotoxicities among cell lines, and that of surface-treated TiO2 was weaker than that of non-treated TiO2. TiO2 located in cytosol might be the main cause of cytotoxicity.