紫外线诱导下二氧化钛纳米颗粒对皮肤的潜在损伤作用及其分子机制研究

The in vivo biological safety of nanomaterials is an important scientific problem which needs to be solved urgently in the field of nanotechnology. Titanium dioxide nanoparticles (TiO2-NPs ) is a kind of materials which closely contact with skin and should be catalyzed by Ultraviolet （UV）to generate phototoxicity. So far, some important problems, whether TiO2-NPs should injure skin and the specific mechanism of the injury, are still unclear. Through establish the UVA-irradiated models of TiO2-NPs contacting with skin and co-culturing with the main cells of skin, this project will investigate the performance of skin injury caused by the TiO2-NPs as well as analyze the direct damage of TiO2-NPs on the keratinocytes (KCs) and the KCs-mediated indirect damage of TiO2-NPs on the dermal fibroblasts (DFs). The changes in the biological characteristics of KCs and DFs are also investigated in this project in order to reveal the molecular mechanism of skin injury caused by TiO2-NPs and describe the interaction among the TiO2-NPs, KCs and DFs. The completion of this project will fill the blank in the field of in vivo biosafety study of nanomaterials and provide a scientific basis to avoid the risks of nanomaterials application and solve the problems which be posed in the application process of nanomaterials.

纳米材料体内生物安全性是纳米技术领域亟待解决的重要科学问题。二氧化钛纳米颗粒（TiO2-NPs）是一种与皮肤密切接触的纳米材料，其在紫外线诱导下对生物体具有光毒性效应。目前，对于TiO2-NPs是否会对皮肤产生损伤作用，以及损伤的具体机制等重要问题尚不清楚。本项目通过建立紫外线诱导下TiO2-NPs皮肤接触和TiO2-NPs与皮肤主要细胞共培养模型，研究TiO2-NPs致皮肤损伤的表现规律，分析TiO2-NPs对角质形成细胞（KCs）的直接损伤作用和经KCs介导对真皮成纤维细胞(DFs)的间接损伤作用，探讨损伤过程中KCs和DFs生物学特征变化情况，揭示TiO2-NPs对皮肤潜在损伤作用的分子机制，阐述接触于皮肤的TiO2-NPs与KCs和DFs三者间相互作用关系的科学问题，填补国内外在纳米材料生物安全性研究领域的空白，为规避纳米材料应用风险和解决应用过程中可能出现的问题提供科学依据。

纳米材料体内生物安全性是纳米技术领域亟待解决的重要科学问题。本项目研究了二氧化钛纳米颗粒（TiO2-NPs）对皮肤的潜在损伤作用及其分子机制。选择粒径为30nm左右的金红石晶型的TiO2-NPs作为研究对象，通过建立紫外线诱导下TiO2-NPs皮肤接触动物实验研究TiO2-NPs对皮肤损伤的病理变化。建立紫外线诱导下，TiO2-NPs与角质形成细胞（KCs）和真皮成纤维细胞(DFs)的共培养模型，通过细胞生物学、分子生物学等实验方法，研究TiO2-NPs对KCs和DFs的损伤作用及其分子机制。结果表明，在紫外线诱导下，TiO2-NPs可以导致皮肤角化层变薄和疏松，降低KCs角蛋白和P53蛋白的表达，并可以通过KCs介导作用间接降低DFs的趋化能力、合成胶原和细胞因子的能力。本研究结果揭示了紫外线诱导下，TiO2-NPs对皮肤的损伤作用及其机制，为规避纳米材料应用风险和解决应用过程中可能出现的问题提供科学依据。