Nanomaterial toxicity tests using normal and cancer cells may yield markedly different results. Here, nanomaterial toxicity between cancer and primary human cells was compared to determine the basic cell line selection criteria for nanomaterial toxicity analyses. Specifically, we exposed two cancer (A549 and HepG2) and two normal cell lines (NHBE and HH) cell lines to SiO₂ nanoparticles (NPs) and evaluated the cytotoxicity (MTS assay), cell death mode, and intracellular NP retention. MTS assay results revealed higher sensitivity of HH cells to SiO₂ NPs than HepG2 cells, while no difference was observed between NHBE and A549 cells. In addition, SiO₂ NPs primarily induced necrosis in all the cell lines. Moreover, we evaluated NP accumulation by treating the cell lines with fluorescein-isothiocyanate-labeled SiO₂ NPs. After 48 h of treatment, less than 10% of A549 and HepG2 cells and more than 30% of NHBE and HH cells contained the labeled NPs. Collectively, our results suggest that cell viability, death mode, and intracellular compound accumulation could be assessed using cancer cells. However, the outcomes of certain investigations, such as intracellular NP retention, may differ between cancer and normal cells.

Silica nanoparticles (SiO₂ NPs) are commonly used in medical and pharmaceutical fields. Research into the cytotoxicity and overall proteomic changes occurring during initial exposure to SiO₂ NPs is limited. We investigated the mechanism of toxicity in human liver cells according to exposure time [0, 4, 10, and 16 h (h)] to SiO₂ NPs through proteomic analysis using mass spectrometry. SiO₂ NP-induced cytotoxicity through various pathways in HepG2 cells. Interestingly, when cells were exposed to SiO₂ NPs for 4 h, the morphology of the cells remained intact, while the expression of proteins involved in mRNA splicing, cell cycle, and mitochondrial function was significantly downregulated. These results show that the toxicity of the nanoparticles affects protein expression even if there is no change in cell morphology at the beginning of exposure to SiO₂ NPs. The levels of reactive oxygen species changed significantly after 10 h of exposure to SiO₂ NPs, and the expression of proteins associated with oxidative phosphorylation, as well as the immune system, was upregulated. Eventually, these changes in protein expression induced HepG2 cell death. This study provides insights into cytotoxicity evaluation at early stages of exposure to SiO₂ NPs through in vitro experiments.

Titanium dioxide nanoparticles (TiO₂ NPs) have wide commercial applications, owing to their small size; however, the biosafety of TiO₂ NPs should be evaluated further. In this study, we aimed to investigate the cytotoxicity of TiO₂ NPs in the presence and absence of ultraviolet A (UVA) irradiation in human keratinocyte HaCaT cells. TiO₂ NPs did not significantly affect cell viability in the absence of UVA irradiation. Nonetheless, UVA-irradiated TiO₂ NPs induced caspase-dependent apoptosis of HaCaT cells. Exposure of HaCaT cells to TiO₂ NPs and UVA resulted in reactive oxygen species (ROS) generation and lysosomal membrane permeabilization (LMP); both effects were not observed in the absence of 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. These results imply that LMP-dependent oxidative stress plays a critical role in the UVA phototoxicity of TiO₂ NPs in HaCaT cells.