Liang Yan, Simaiti Aili, Xu Mingxuan, Lv Shenchong, Jiang Hui, He Xiaoxiang, Fan Yang, Zhu Shaoxiong, Du Binyang, Yang Wei, Li Xiaolin, Yu Peilin
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Lishui International Travel Health-Care Center, Lishui 323000, China.
Nanomaterials (Basel). 2022 Aug 12;12(16):2769. doi: 10.3390/nano12162769.
Being the main components of physical sunscreens, zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO NPs) are often used together in different brands of sunscreen products with different proportions. With the broad use of cosmetics containing these nanoparticles (NPs), concerns regarding their joint skin toxicity are becoming more and more prominent. In this study, the co-exposure of these two NPs in human-derived keratinocytes (HaCaT) and the in vitro reconstructed human epidermis (RHE) model EpiSkin was performed to verify their joint skin effect. The results showed that ZnO NPs significantly inhibited cell proliferation and caused deoxyribonucleic acid (DNA) damage in a dose-dependent manner to HaCaT cells, which could be rescued with co-exposure to TiO NPs. Further mechanism studies revealed that TiO NPs restricted the cellular uptake of both aggregated ZnO NPs and non-aggregated ZnO NPs and meanwhile decreased the dissociation of Zn from ZnO NPs. The reduced intracellular Zn ultimately made TiO NPs perform an antagonistic effect on the cytotoxicity caused by ZnO NPs. Furthermore, these joint skin effects induced by NP mixtures were validated on the epidermal model EpiSkin. Taken together, the results of the current research contribute new insights for understanding the dermal toxicity produced by co-exposure of different NPs and provide a valuable reference for the development of formulas for the secure application of ZnO NPs and TiO NPs in sunscreen products.
作为物理防晒剂的主要成分，氧化锌纳米颗粒（ZnO NPs）和二氧化钛纳米颗粒（TiO NPs）常以不同比例共同用于不同品牌的防晒产品中。随着含有这些纳米颗粒（NPs）的化妆品的广泛使用，关于它们联合皮肤毒性的担忧日益突出。在本研究中，对这两种纳米颗粒在人源角质形成细胞（HaCaT）和体外重建人表皮（RHE）模型EpiSkin中进行共同暴露，以验证它们的联合皮肤效应。结果表明，ZnO NPs显著抑制细胞增殖，并以剂量依赖的方式对HaCaT细胞造成脱氧核糖核酸（DNA）损伤，而与TiO NPs共同暴露可挽救这种损伤。进一步的机制研究表明，TiO NPs限制了聚集态ZnO NPs和非聚集态ZnO NPs的细胞摄取，同时减少了Zn从ZnO NPs的解离。细胞内Zn的减少最终使TiO NPs对ZnO NPs引起的细胞毒性产生拮抗作用。此外，在表皮模型EpiSkin上验证了NP混合物诱导的这些联合皮肤效应。综上所述，当前研究结果为理解不同纳米颗粒共同暴露产生的皮肤毒性提供了新的见解，并为开发在防晒产品中安全应用ZnO NPs和TiO NPs的配方提供了有价值的参考。
