Assessment of penetration depth and toxicity of titanium dioxide nanoparticles in barrier-defective skin after UV exposition

紫外线照射后二氧化钛纳米粒子在屏障缺陷皮肤中的渗透深度和毒性评估

• 批准号: 506860058
• 负责人: Professor Dr. Steffen Emmert
• 金额: --
• 依托单位: Klinik und Poliklinik für Dermatologie und Venerologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/506860058?language=en
• 关键词: Assessment; penetration; depth; toxicity; titanium

The photocatalytic activity of titanium dioxide nanoparticles under UV irradiation in the presence of water leads to the formation of genetically harmful reactive oxygen species (ROS). Titanium dioxide nanoparticles are used in cosmetics and sunscreens. While they do not penetrate the skin barrier in healthy skin, they may be able to penetrate the outermost layer of the epidermis (stratum corneum) and enter living layers of the skin suffering from diseases which limit its natural barrier function. There is reason to fear that even small amounts of photocatalytically active particles reaching living tissue, lead to the formation of aggressive ROS, especially under UV irradiation. These can then damage the cells and the genetic material in the deeper layers of the skin and thus increase the risk of skin cancer. While extensive studies have shown that sunscreens containing nanoscale titanium dioxide particles can be safely applied to healthy, undamaged skin, the safe use of sunscreens on disease-damaged skin or skin stressed by sunburn, wind, salt water or sand is still unclear. Therefore the aim of this project is to contribute to the assessment of the risk posed by sunscreens and cosmetic products containing titanium dioxide nanoparticles to patients with barrier-damaged skin.In joint preliminary work, the applicants have succeeded in testing total reflection X-ray fluorescence spectroscopy (TXRF) as a suitable method for detecting titanium in microtome sections of skin samples. Using a combination of XRF methods and Raman microscopy, it is possible to trace diffusion profiles of titanium dioxide nanoparticles in damaged skin. It has also been demonstrated that frozen skin samples treated with sunscreens can be cut with a focused ion beam and subsequently analyzed in a cryo-scanning electron microscope.The proposed project will start with the analysis of the photocatalytic reactions in UV-irradiated cell cultures covered with titanium dioxide nanoparticles. The determination of the penetration depth of titanium dioxide nanoparticles in barrier-disturbed skin after UV irradiation in comparison to healthy skin in a mouse model and using human skin samples as an example, forms the core of the investigations. Furthermore, the influence of titanium dioxide nanoparticles on epidermal differentiation, proliferation, stability and integrity will be investigated and DNA lesions will be identified and characterized. The new findings on the penetration depth and toxicity of titanium dioxide nanoparticles in barrier-disturbed skin will make an important contribution to improved risk assessment for the use of cosmetics containing titanium dioxide, especially sunscreens, for patients with skin barrier disorders.

二氧化钛纳米粒子在紫外光照射下的光催化活性在水的存在下导致形成遗传有害的活性氧物种（ROS）。二氧化钛纳米颗粒用于化妆品和防晒霜。虽然它们不能穿透健康皮肤中的皮肤屏障，但它们可能能够穿透表皮的最外层（角质层）并进入患有限制其天然屏障功能的疾病的皮肤的活层。有理由担心，即使是少量的光催化活性颗粒到达活组织，也会导致形成侵略性的ROS，特别是在紫外线照射下。这些会破坏皮肤深层的细胞和遗传物质，从而增加患皮肤癌的风险。虽然广泛的研究表明，含有纳米级二氧化钛颗粒的防晒霜可以安全地应用于健康、未受损的皮肤，但防晒霜在疾病受损的皮肤或因晒伤、风、盐水或沙子而受到压力的皮肤上的安全使用仍不清楚。因此，本项目的目的是评估含有二氧化钛纳米粒子的防晒霜和化妆品对皮肤屏障受损患者的风险。在联合前期工作中，申请人成功地测试了全反射X射线荧光光谱（TXRF），作为检测皮肤样品切片中钛的合适方法。使用XRF方法和拉曼显微镜的组合，可以追踪二氧化钛纳米颗粒在受损皮肤中的扩散分布。研究还表明，用防晒霜处理过的冷冻皮肤样本可以用聚焦离子束切割，随后在冷冻扫描电子显微镜中进行分析。拟议的项目将从分析覆盖有二氧化钛纳米颗粒的紫外线照射细胞培养物中的光催化反应开始。与小鼠模型中的健康皮肤相比，并以人类皮肤样品为例，确定紫外线照射后二氧化钛纳米颗粒在屏障干扰皮肤中的渗透深度，形成了研究的核心。此外，将研究二氧化钛纳米颗粒对表皮分化、增殖、稳定性和完整性的影响，并鉴定和表征DNA损伤。关于二氧化钛纳米颗粒在屏障受损皮肤中的渗透深度和毒性的新发现将为改善皮肤屏障疾病患者使用含二氧化钛化妆品（尤其是防晒霜）的风险评估做出重要贡献。