Investigating the accumulation and translocation of titanium dioxide nanoparticles with different surface...

Titanium dioxide nanoparticles (TiO₂ NPs) are widely incorporated in various consumer products such as cosmetics and food. Despite known human exposure, the potential risks of TiO₂ NPs during pregnancy are not fully understood, but several studies in mice elucidated toxic effects on fetal development. It has also been shown that modifying NPs with positive or negative surface charge alters cellular uptake and abolishes fetotoxicity of silicon dioxide (SiO₂) NPs in mice. Here, we investigated accumulation and translocation of positively charged TiO₂-NH₂ and negatively charged TiO₂-COOH NPs at the placental barrier, to clarify whether surface charge provides a means to control TiO₂ NP distribution at the placental barrier. To ensure outcome relevant for humans, the recently developed in vitro human placental co-culture model and the gold standard amongst placental translocation models - the ex vivo perfusion of human term placental tissue - were employed during this study. Sector field-ICP-MS analysis of maternal and fetal supernatants as well as placental cells/tissues revealed a substantial accumulation of both TiO₂ NP types while no considerable placental translocation was apparent in both models. Characterization of agglomeration behavior demonstrated a strong and fast agglomeration of TiO₂-NH₂ and TiO₂-COOH NPs in the different culture media. Overall, our results indicate that surface charge is not a key factor to steer placental uptake and transfer of TiO₂. Moreover, the negligible placental transfer but high accumulation of TiO₂ NPs in placental tissue suggests that potential effects on fetal health may occur indirectly, which calls for further studies elucidating the impact of TiO₂ NPs on placental tissue functionality and signaling.