Does photocatalytic activity of TiO₂ nanoparticles correspond to photo-cytotoxicity? Cellular uptake of TiO₂ nanoparticles is important in their photo-cytotoxicity

Abstract

Titanium dioxide (TiO2) nanoparticles are important industrial nano-objects with wide applications, including as photocatalysts and sunscreen components. Recently, the phototoxicity of TiO2 nanoparticles has been a concern. However, phototoxicity caused by photocatalytic activity may differ between anatase and rutile nanoparticles. In the present study, we compared the phototoxicity of anatase and rutile nanoparticles. Human keratinocyte HaCaT cells were treated with stable TiO2 nanoparticle suspensions. Without UVA irradiation, TiO2 nanoparticles did not affect mitochondrial activity or cell membranes. However, exposure to rutile nanoparticle suspensions inhibited cell growth and induced HO-1 gene expression without UVA irradiation. These effects may be explained by the hydrophobic surface of rutile nanoparticles. Next, TiO2-exposed cells were irradiated with UVA for 4 h and effects of TiO2 nanoparticles on cells were examined. The rutile nanoparticles did not show any cellular effects after UVA irradiation. However, the anatase nanoparticles caused strong phototoxicity. Decreased mitochondrial activity, cell membrane damage and the induction of oxidative stress were observed in the cells exposed to anatase nanoparticles with UVA irradiation. Cellular uptake of the nanoparticles was observed in both anatase- and rutile-exposed cells. These results suggest that internalized anatase nanoparticles are important for phototoxicity. Additionally, the exposure of a 3D skin model to TiO2 nanoparticles did not result in significant toxicity. In conclusion, rutile nanoparticles used in sunscreen did not exhibit phototoxic activity. Despite the strong phototoxic activity of anatase nanoparticles in cell cultures, they demonstrated no phototoxicity using a 3D skin model.

Safety of titanium dioxide nanoparticles in cosmetics

“…When several nano‐TiO 2 concentrations were tested, a dose‐dependent effect was observed. On the contrary, five studies reported no effect of nano‐TiO 2 (0.1–25 μg/cm 2 or 1–100 μg/mL) on HaCaT cell viability after 2–24 h of exposure, but one of them showed a dose‐dependent increase in apoptosis . Data on nano‐TiO 2 cytotoxicity assessed in human skin cells are presented in Table .…”

“…ROS induction in HaCaT cells was shown to be enhanced by UVA and UVB irradiation, but not by UVC irradiation, thus demonstrating phototoxicity of nano‐TiO 2 to human skin keratinocytes. Interestingly, after UVA irradiation, either less or no phototoxicity was observed in HaCaT cells with the rutile form of nano‐TiO 2 in comparison with the anatase form . Of note, no phototoxicity was observed with the anatase form of nano‐TiO 2 in the EpiDerm ™ 3D skin model In contrast to the HaCaT cell line that consists of human immortalized keratinocytes, the EpiDerm™ 3D model is a reconstructed human epidermis with normal human‐derived epidermal keratinocytes that is expected to provide a more integrated response.…”

Toxicity Evaluation of TiO2 Nanoparticles on the 3D Skin Model: A Systematic Review

“…After duplicates removal, 31 studies had their titles and abstracts screened, and 24 studies were excluded because they did not meet the eligibility criteria. Then, the full-text screening did not exclude any studies, resulting in 7 included articles (Park et al, 2011;Choi et al, 2014;Kato et al, 2014;Horie et al, 2016;Kim et al, 2016;Miyani and Hughes, 2016;Tang et al, 2018) in this systematic review (Figure 3 Prisma Flow diagram).…”

Effects of differently shaped TiO2NPs (nanospheres, nanorods and nanowires) on the in vitro model (Caco-2/HT29) of the intestinal barrier

“…The European Food Safety Authority (EFSA) designated the “E number” E171 to TiO 2 , granting it as a substance that can be used as a food additive [ 2 ]. In addition, recent evidence indicates that the use of nanosized titanium dioxide (TiO 2 NPs) in consumer and industrial products has exponentially increased due to their highly valuable refractive, photocatalytic and pigmenting properties [ 3 , 4 ]. Even though TiO 2 was classified by the International Agency for Research on Cancer (IARC) as a possible human carcinogen on group 2B in 2010, the Nanotechnology Consumer Products Inventory has documented around 100 consumer products containing TiNPs and TiO 2 NPs to date [ 5 ].…”