Size- and shape-dependent effects of titanium dioxide nanoparticles on the permeabilization of the blood–brain barrier†
Titanium dioxide nanoparticles (TiO2-NPs) have been found to translocate into the brain by penetrating the blood–brain barrier (BBB), but it remains largely unknown how their physicochemical characteristics may impact BBB permeabilization. By testing TiO2 particles of different shapes and various sizes, we found that: (1) small, spherical TiO2-NPs permeabilized a BBB-like human brain microvasculature endothelial cell monolayer better than rod-like or large particles; (2) TiO2-NPs stimulated F-actin stress fiber formation, and induced paracellular gaps and ROCK II activation. The TiO2-NP-mediated BBB permeabilization was associated with intracellular uptake and cytoskeletal re-organization; and (3) in rats, spherical, small TiO2-NPs significantly increased the BBB permeability and entered the brain. The TiO2-NPs were accumulated in the brain, but no obvious pathological anomaly was observed in the cerebral cortex and hippocampus. Our study investigated the neurotoxicity of TiO2-NPs, thereby providing scientific evaluation for the potential biomedical applications of TiO2-NPs.