School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Ave, Singapore, 639798, Singapore.
Nanyang Environment and Water Research Institute, Cleantech Loop 1, Singapore, 637141, Singapore.
Arch Toxicol. 2024 Nov;98(11):3689-3711. doi: 10.1007/s00204-024-03848-6. Epub 2024 Aug 26.
The use of metal oxide nanoparticles (NPs) in skincare products has significantly increased human skin exposure, raising safety concerns. Whilst NP's ability to penetrate healthy skin is minimal, studies have demonstrated that metal oxide NPs can induce toxicity in keratinocytes through direct contact. Moreover, NP's effect on common skin disorders like psoriasis, where barrier impairments and underlying inflammation could potentially increase NP penetration and worsen nanotoxicity is largely unstudied. In this paper, we investigated whether psoriasis-like human keratinocytes (Pso HKs) would exhibit heightened toxic responses to titanium dioxide (TiO), zinc oxide (ZnO), and/or silica (SiO) NPs compared to healthy HKs. Cells were exposed to each NP at concentrations ranging between 0.5 and 500 µg/ml for 6, 24, and 48 h. Amongst the metal oxide NPs, ZnO NPs produced the most pronounced toxic effects in both cell types, affecting cell viability, inducing oxidative stress, and activating the inflammasome pathway. Notably, only in ZnO NPs-treated Pso HKs, trappin-2/pre-elafin was cleaved intracellularly through a non-canonical process. In addition, tissue remodelling-related cytokines were upregulated in ZnO NP-treated Pso HKs. The full impact of the observed outcomes on psoriatic symptoms will need further evaluation. Nonetheless, our findings indicate the importance of understanding the sub-lethal impacts of NP exposures on keratinocytes, even though direct exposure may be low, particularly in the context of skin disorders where repeated and long-term exposures are anticipated.
金属氧化物纳米粒子（NPs）在护肤品中的应用显著增加了人体皮肤的暴露程度，引发了安全问题。虽然 NP 穿透健康皮肤的能力很有限，但研究表明，金属氧化物 NPs 可以通过直接接触诱导角质细胞产生毒性。此外，NP 对常见皮肤疾病（如银屑病）的影响，在这些疾病中，屏障损伤和潜在炎症可能会增加 NP 的穿透性并加重纳米毒性，这方面的研究还很少。在本文中，我们研究了银屑病样人角质细胞（Pso HKs）是否会对二氧化钛（TiO）、氧化锌（ZnO）和/或二氧化硅（SiO） NPs 产生比健康 HKs 更高的毒性反应。细胞分别暴露于每种 NP 的浓度范围为 0.5 至 500μg/ml 下 6、24 和 48 小时。在金属氧化物 NPs 中，ZnO NPs 在两种细胞类型中产生了最显著的毒性作用，影响细胞活力，诱导氧化应激，并激活炎症小体途径。值得注意的是，只有在 ZnO NPs 处理的 Pso HKs 中，trappin-2/pre-elafin 通过非经典途径在内质网中被切割。此外，在 ZnO NP 处理的 Pso HKs 中，组织重塑相关细胞因子被上调。需要进一步评估观察结果对银屑病症状的全面影响。尽管如此，我们的研究结果表明，即使直接暴露可能较低，尤其是在预期会出现重复和长期暴露的皮肤疾病背景下，了解 NP 暴露对角质细胞的亚致死影响的重要性。
