Dongguan People's Hospital Biobank, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Guangzhou, Guangdong, 510515, China.
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue, Guangzhou, Guangdong, 510515, China.
Food Chem Toxicol. 2024 Nov;193:114948. doi: 10.1016/j.fct.2024.114948. Epub 2024 Aug 26.
ZnO nanoparticles (NPs) are used in skin treatments and cosmetics, the toxicity of long-term and continuous exposure to ZnO NPs is unknown. Mice with epidermal barrier dysfunction revealed melanoma-like lesions after continuous exposure to ZnO NPs. However, the effects of metallic NPs on the skin microenvironment and immune system remain poorly understood. Mice with epidermal barrier failure were given continuous exposure to ZnO NPs for 7 weeks. The malignant transformation of melanocytes was induced with ZnO NPs 2.5 μg/ml for 72 h exposure. The supernatant of the culture medium from dendritic cells after being exposed to 10 μg/ml ZnO NPs for 24 h was applied to melanocytes to explore the effect of recruitment of DCs. The expressure of ZnO NPs resulted in a tendency of malignant transformation of melanocytes, the recruitment of DCs induces this process by produce inflammatory factors such as TNF-α. These DC-produced inflammatory factors, which were induced by ZnO NP exposure, increased the production of matrix metalloproteinases in melanocytes and expedited the malignant transformation process. Our findings revealed that the disrupted cutaneous microenvironment by ZnO NPs penetrated directly promoted the malignant transformation of melanocytes, which process also indirectly enhanced by the TNF-αsecreted from the recruited DCs.
氧化锌纳米粒子（NPs）被用于皮肤治疗和化妆品中，然而，长期和持续暴露于 ZnO NPs 的毒性尚不清楚。表皮屏障功能障碍的小鼠在持续暴露于 ZnO NPs 后表现出类似黑色素瘤的病变。然而，金属 NPs 对皮肤微环境和免疫系统的影响仍知之甚少。我们使表皮屏障功能障碍的小鼠持续暴露于 ZnO NPs 7 周。用 2.5μg/ml 的 ZnO NPs 暴露 72 小时诱导黑素细胞的恶性转化。用 10μg/ml ZnO NPs 孵育 24 小时后，将树突状细胞培养上清液应用于黑素细胞，以探讨 DC 募集的影响。ZnO NPs 的表达导致黑素细胞恶性转化的趋势，DC 的募集通过产生 TNF-α 等炎症因子诱导这一过程。这些由 ZnO NP 暴露引起的 DC 产生的炎症因子增加了黑素细胞中基质金属蛋白酶的产生，并加速了恶性转化过程。我们的研究结果表明，ZnO NPs 破坏的皮肤微环境直接促进了黑素细胞的恶性转化，而 TNF-α 等炎症因子的分泌也间接增强了这一过程。
