Abstract
Background Titanium dioxide nanoparticles (TiO2 NPs) are important nanomaterials with wide commercial applications. While the small size of TiO2 NPs is useful in various applications, their biosafety should be evaluated further. In this study, we investigated the cytotoxicity of TiO2 NPs in the presence and absence of UVA irradiation in human keratinocyte HaCaT cells.Results TiO2 NPs did not significantly affect cell viability in the absence of UVA irradiation. However, UVA-irradiated TiO2 NPs induced caspase-dependent apoptosis. Exposure of HaCaT cells to TiO2 NPs and UVA resulted in reactive oxygen species (ROS) generation, and lysosomal membrane permeabilization (LMP); both effects were absent without UVA irradiation. An analysis of the relationship between LMP and ROS, using CA-074 as a cathepsin inhibitor or NAC as an antioxidant, showed that LMP stimulates ROS generation under these conditions.Conclusion These results imply that LMP-dependent oxidative stress plays a critical role in the UVA phototoxicity of TiO2 NPs in HaCaT cells.