BSA Adsorption on Titanium Dioxide Nanoparticle Surfaces for Controlling Their Cellular Uptake in Skin Cells

Nanoparticles (NPs) are continuously being developed for many applications including imaging, biomedicine, and everyday products. It is difficult to avoid contact with NPs such as titanium dioxide (TiO₂) NPs, which are widely used in sunscreens. However, the safety of TiO₂ NPs for skin contact and inhalation remains controversial. If NPs cannot penetrate the skin, they will be unable to circulate in the bloodstream, accumulate in the body, or cause side effects, ensuring their safety. Therefore, this study aimed to modify TiO₂ NP surfaces to inhibit their uptake in skin cells. Inspired by protein corona studies, bovine serum albumin (BSA) was chosen to functionalize TiO₂ NP surfaces via physical adsorption. The maximum BSA adsorption occurred at pH 5.0. The physicochemical properties (size, ζ-potential, morphology, ultraviolet (UV) absorption efficiency, and sun protection factor (SPF)) of TiO₂-BSA NPs were comparable to those of TiO₂ NPs, indicating that these properties did not affect cellular uptake. In the safety evaluation, TiO₂ NPs and TiO₂-BSA NPs exhibited high biocompatibility with skin cells and no phototoxicity after UVA and UVB irradiation. In the efficacy evaluation, both NPs possessed the same photoprotection abilities, reducing membrane damage and DNA breakage after UVA irradiation. Compared with TiO₂ NPs, TiO₂-BSA NPs showed substantially reduced skin penetration in Franz diffusion cells (91%) and human immortalized keratinocyte (HaCaT) cells (89%). A qualitative cellular uptake study using transmission electron microscopy and confocal laser scanning microscopy confirmed that TiO₂ NPs were more abundant than TiO₂-BSA NPs inside the HaCaT cells. These findings indicate that TiO₂ surface functionalization with BSA inhibits cellular uptake in skin cells while maintaining safety and UV protection efficacy, which might be extended to other NP-based sunscreens.