Antagonistic Skin Toxicity of Co-Exposure to Physical Sunscreen Ingredients Zinc Oxide and Titanium Dioxide Nanoparticles
Yan Liang,
Aili Simaiti,
Mingxuan Xu,
Shenchong Lv,
Hui Jiang,
Xiaoxiang He,
Yang Fan,
Shaoxiong Zhu,
Binyang Du,
Wei Yang,
Xiaolin Li,
Peilin Yu
Affiliations
Yan Liang
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Aili Simaiti
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Mingxuan Xu
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Shenchong Lv
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Hui Jiang
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Xiaoxiang He
Lishui International Travel Health-Care Center, Lishui 323000, China
Yang Fan
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Shaoxiong Zhu
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science & Engineering, Zhejiang University, Hangzhou 310027, China
Binyang Du
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science & Engineering, Zhejiang University, Hangzhou 310027, China
Wei Yang
Department of Biophysics, Zhejiang University School of Medicine, Hangzhou 310058, China
Xiaolin Li
Technical Center of Animal, Plant and Food Inspection and Quarantine of Shanghai Customs, Shanghai 200135, China
Peilin Yu
Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Being the main components of physical sunscreens, zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 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 TiO2 NPs. Further mechanism studies revealed that TiO2 NPs restricted the cellular uptake of both aggregated ZnO NPs and non-aggregated ZnO NPs and meanwhile decreased the dissociation of Zn2+ from ZnO NPs. The reduced intracellular Zn2+ ultimately made TiO2 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 TiO2 NPs in sunscreen products.