Differential analysis of the role of surface properties and cellular uptake of metal oxides in their nanoform for their cytocompatibility by means of synthesized micro-nanostructures

纳米材料在消费品、医药和环境中的使用越来越多，由于新材料的特性，带来了新的好处，但也带来了风险。小粒径允许摄取到细胞中并通过身体屏障。此外，相对于其质量，纳米颗粒的相对大的活性表面增强了其与细胞和组织结构的可能相互作用，这可能诱导或增强不希望的效应。只有深入了解这些相互作用，才有可能利用巨大的潜力，同时降低健康风险。金属氧化物经常用于纳米材料，因为合成过程相对快速，简单和便宜，并且可以实现许多可变的材料特性。提交提案的目的是检查金属氧化物纳米材料在各种细胞培养模型中毒性的细胞摄取和表面性质的意义，以确定具有最小毒性潜力的材料结构。因此，将比较由可被细胞摄取的常规金属氧化物纳米颗粒和具有相同表面积但不能被细胞摄取的特殊金属氧化物微纳米结构诱导的细胞功能的变化。微纳米结构是在我们实验室通过火焰传输合成法合成的，通常由一个微米大小的核和多个纳米大小的过程组成。亚致死浓度的金属氧化物将用于来自屏障器官的人类细胞系的细胞培养模型中（肠、肺、皮肤）和免疫活性细胞，以检查病理相关效应，如活力，炎症，细胞内化的纳米颗粒和非内化的微米-纳米结构的毒理学效应的比较将有助于推导出细胞摄取对于其纳米尺寸的金属氧化物的毒性的相关性。这将是可能的，因为模型中的表面积可以在两个系统中保持恒定，因为细胞颗粒摄取和颗粒表面积的正常相关变量此外，材料表面性质对微纳米结构金属氧化物的生物效应的影响，我们的研究结果将有助于理解纳米材料的毒理学机制，并将帮助材料科学家在金属氧化物纳米结构的发展过程中考虑可能的毒理学效应。

Increasing use of nanomaterials in consumer products, medicine and the environment involves due to new material properties new benefits but also risks. The small particle size permits uptake into cells and passing body barriers. Furthermore, the relatively large and active surface of nanoparticles referring to their mass potentiates their possible interactions with cell- and tissue structures, which might induce or enhance unwanted effects. Only an in-depth understanding of these interactions will make it possible to utilise the big potential and to reduce health risk at the same time.Metal oxides are frequently used for nanomaterials as the synthesis is a relatively fast, simple and cheap process and many variable material properties can achieved. The goal of the submitted proposal is to examine the meaning of cellular uptake and surface properties of metal oxide nanomaterials for their toxicity in various cell culture models to identify those material structures with minimal potential of toxicity. Therefore, changes of cell functions induced by conventional metal oxide nanoparticles, which can be taken up by cells, and special metal oxide micro-nanostructures having the same surface area, but cannot be taken up by cells, will be compared. The micro-nanostructures are synthesized in our lab by flame transport synthesis and consist typically of a micrometer-sized nucleus with multiple nano-sized processes.Sublethal concentrations of metal oxides will be used in cell culture models of human cell lines derived from barrier organs (intestine, lung, skin) and immunocompetent cells to examine pathologically relevant effects like viability, inflammation, oxidative stress or altered cell proliferation.Comparison of toxicological effects of cell-internalized nanoparticles and non-internalized micro-nanostructures will help to derive the relevance of cellular uptake for the toxicity of metal oxides in their nanosize. This will be possible as the surface area in the models can be held constant in both systems, because the normally dependent variables of cellular particle uptake and particle surface area (via the particle diameter) can be uncoupled despite of continued direct cell contact.Moreover, the impact of material surface properties on biological effects of micro-nanostructured metal oxides, which we are able to modify systematically in our lab will be examined.Our findings will contribute to understand toxicological mechanisms of nanomaterials and will help material scientists to consider possible toxicological effects already during the development of metal oxide nanostructures.