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

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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.