De Kwek Darien Yu, Setyawati Magdiel Inggrid, Gautam Archana, Adav Sunil S, Cheong Ee Cherk, Ng Kee Woei
School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
Interdisciplinary Graduate Programme (IGP), Graduate College, Singapore, Singapore.
Part Fibre Toxicol. 2024 Dec 4;21(1):49. doi: 10.1186/s12989-024-00610-9.
Inorganic ultraviolet filters such as titanium dioxide nanoparticles are frequently used in sunscreens. Numerous toxicological studies in vitro and in vivo have been conducted using pristine standard reference nanomaterials of these inorganic filters. While convenient, this approach is not realistic because the complex environment of sunscreen formulations could change the physicochemical properties of the nanoparticles and lead to vastly different toxicological outcomes. Therefore, this study focused on characterizing nanoparticles extracted from commercial sunscreen and evaluating the associated toxicological impacts upon exposure to human keratinocytes and human skin explants.
Titanium dioxide nanoparticles were extracted from commercial sunscreens and thoroughly characterized. The identity of the associated molecular corona on the extracted nanoparticles was also evaluated. Cell metabolic and proliferation profiles, mitochondrial superoxide activity, reactive oxygen species levels, and genotoxicity induced through exposure to the nanoparticles were studied in vitro using a human keratinocyte cell line. The cell response was significantly different after treatment with pristine nanoparticles compared to corresponding sunscreen-extracted nanoparticles. Pristine spherical nanoparticles resulted in more pronounced toxicity in 2D cultured keratinocytes compared to extracted nanoparticles but did not impact wound-edge migration significantly in 3D ex vivo human skin explant models. Additionally, extracted rod-shaped nanoparticles had greater toxic impacts in keratinocytes in vitro and retarded wound-edge migration in the ex vivo model compared to the extracted spherical nanoparticles. Nevertheless, these heightened cell responses were not associated with any increase in phosphorylated γHAX (which is indicative of DNA damage) both in vitro and ex vivo.
This study shows the feasibility of extracting nanoparticles from personal care products such as sunscreens to obtain relevant forms to model real-life exposure scenarios. Overall, sunscreen-extracted nanoparticles were found to be less toxic compared to pristine equivalents but retarded wound-edge migration more significantly. Skin explant cultures provide a more realistic alternative to monolayer cell cultures, although the differential outcomes between the models need more in-depth evaluation.
无机紫外线过滤剂,如二氧化钛纳米颗粒,常用于防晒霜中。已使用这些无机过滤剂的原始标准参考纳米材料进行了大量体外和体内毒理学研究。虽然这种方法很方便,但并不现实,因为防晒霜配方的复杂环境可能会改变纳米颗粒的物理化学性质,并导致截然不同的毒理学结果。因此,本研究着重于对从商业防晒霜中提取的纳米颗粒进行表征,并评估其对人角质形成细胞和人皮肤外植体暴露后的相关毒理学影响。
从商业防晒霜中提取了二氧化钛纳米颗粒并进行了全面表征。还评估了提取的纳米颗粒上相关分子冠的特性。使用人角质形成细胞系在体外研究了通过暴露于纳米颗粒诱导的细胞代谢和增殖谱、线粒体超氧化物活性、活性氧水平和遗传毒性。与相应的从防晒霜中提取的纳米颗粒相比,用原始纳米颗粒处理后细胞反应有显著差异。与提取的纳米颗粒相比,原始球形纳米颗粒在二维培养的角质形成细胞中产生更明显的毒性,但在三维离体人皮肤外植体模型中对伤口边缘迁移没有显著影响。此外,与提取的球形纳米颗粒相比,提取的棒状纳米颗粒在体外角质形成细胞中有更大的毒性影响,并且在离体模型中延迟了伤口边缘迁移。然而,这些增强的细胞反应在体外和体内均与磷酸化γHAX(指示DNA损伤)的任何增加无关。
本研究表明从防晒霜等个人护理产品中提取纳米颗粒以获得模拟现实生活暴露场景的相关形式的可行性。总体而言,发现从防晒霜中提取的纳米颗粒与原始纳米颗粒相比毒性较小,但对伤口边缘迁移的延迟更显著。皮肤外植体培养为单层细胞培养提供了更现实的替代方法,尽管模型之间的差异结果需要更深入的评估。