Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs. We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release. However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. Our findings propose a new concept for ZnONP-induced skin toxicity mechanisms and the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.

中文翻译：

---

UVB 照射引起的皮肤损伤后，氧化锌纳米粒子通过上调 M1 巨噬细胞中的促炎细胞因子和外泌体分泌来加剧皮肤上皮细胞损伤

氧化锌纳米颗粒（ZnONP）由于具有美白和强紫外线吸收特性，是皮肤相关化妆品和防晒产品中常用的材料。尽管 ZnONP 对完整皮肤的紫外线保护作用已得到充分证明，但使用 ZnONP 对受损或晒伤皮肤的效果仍不清楚。在这项研究中，我们旨在揭示与暴露于 UVB 和 ZnONP 的角质形成细胞和巨噬细胞相关的详细潜在机制。我们证明，ZnONP 会加剧 UVB 照射后小鼠皮肤损伤，进而导致经皮失水 (TEWL) 水平、细胞死亡和上皮厚度增加。此外，ZnONPs 可以穿透受损的上皮，进入真皮细胞，并通过激活 M1 巨噬细胞导致严重的炎症。机制研究表明，角质形成细胞同时暴露于 UVB 和 ZnONPs 会导致溶酶体损伤和自噬功能障碍，从而增加细胞外泌体的释放。然而，这些外泌体可以被巨噬细胞吸收，从而加速 M1 巨噬细胞极化。此外，ZnONPs 还诱导 M1 巨噬细胞产生持久的炎症反应，并通过调节自噬介导的 NLRP3 炎症小体和巨噬细胞外泌体分泌影响上皮细胞修复。我们的研究结果提出了 ZnONP 诱导的皮肤毒性机制和 ZnONP 在脆弱皮肤上应用的安全问题的新概念。该过程涉及溶酶体损伤、自噬介导的 NLRP3 炎性体和巨噬细胞外泌体分泌的相互作用。目前的发现对于评估 ZnONP 在化妆品应用中的效果很有价值。