Interaction of metal oxide nanoparticles with the physical and biochemical barrier function of the human intestine and liver

我们基于银纳米颗粒的初步工作表明，人体消化对到达小肠吸收上皮的纳米级银的形状和性质具有强烈影响，所述纳米级银纳米颗粒是来自非必需材料的良好模型颗粒。此外，银纳米颗粒的涂层、表面纹理和核心材料是肠细胞摄取和转运的重要因素。但就食物而言，其他金属如铁或锌发挥着更重要的作用。它们作为必需的微量元素，用于营养补充剂和医疗应用。由于许多铁盐的生物利用度低，纳米颗粒形式被越来越多地使用。然而，关于这种纳米颗粒的消化和肠道摄取和转运的影响知之甚少。此外，除了选择性的物理化学和机械屏障外，肠上皮还充当异生物质化合物和药物的生化代谢屏障。然而，食品相关的纳米颗粒对这一生化屏障的影响尚未得到广泛的研究。然而，有一个开放的问题，可能干扰代谢相关的细胞信号转导，相关的转录外源性代谢相关酶以及转运蛋白。因此，本项目的目的是回答以下关于食物相关的氧化铁和氧化锌纳米颗粒与生化屏障的消化、摄取和运输以及可能的相互作用的问题：1）消化：人类消化和食物模拟对口服纳米颗粒和离子铁和锌化合物到达肠上皮的物种有什么影响？消化对这些金属在肠道中的吸收和运输有什么影响？2)摄取和运输：纳米颗粒涂层和核心材料独立影响细胞摄取到肠上皮细胞或运输通过肠屏障的假设应该得到验证。3）相互作用：亚毒性浓度的这种纳米颗粒如何改变生化代谢屏障功能，从而影响外源性物质和药物的生物利用度和毒性？这些调查旨在帮助回答有关金属氧化物纳米颗粒对人类构成潜在危害的悬而未决的问题。其目的是填补有关氧化铁和氧化锌纳米颗粒口服吸收的分子机制的知识空白。

Our preliminary work based on silver nanoparticles, which are a good model particle from a non-essential material, has shown that human digestion has a strong influence on the shape and properties of nano-scaled silver that reaches the resorptive epithelium in the small intestine. Additionally, the coating, surface texture and core material of silver nanoparticles are important factors for uptake and transport at the enterocytes. But in terms of food, other metals such as iron or zinc play a more important role. They function as essential trace elements and are used in nutritional supplements as well as for medical applications. Due to the low bioavailability of many iron salts, nanoparticulate forms are increasingly used. However, very little is known about the effect of digestion and intestinal uptake and transport of such nanoparticles. Moreover, in addition to the selective physicochemical and mechanical barrier, the intestinal epithelium also functions as a biochemical-metabolic barrier for xenobiotic compounds and drugs. However, the impact of food-related nanoparticles on this biochemical barrier has not been extensivley investigated. Nevertheless, there are open questions regarding a possible interference with the metabolism-relevant cellular signal transduction, the associated transcription of xenobiotic-metabolism-associated enzymes as well as transporters. Therefore, the aim of this project is to answer the following questions concerning the digestion, uptake and transport as well as the possible interaction of food-relevant iron oxide and zinc oxide nanoparticles with the biochemical barrier:1) Digestion: What influence has human digestion and food simulats on the species in which orally taken up nanoparticulate and ionic iron and zinc compounds reach the intestinal epithelium? What influence does digestion have on the uptake and transport of these metals in the intestine?2) Uptake and Transport: The hypothesis that nanoparticle coating and core material independently influence cellular uptake into enterocytes or transport across the intestinal barrier should be verified.3) Interaction: How do subtoxic concentrations of such nanoparticles alter the biochemical-metabolic barrier function and thus influence the bioavailability and toxicity of xenobiotics and drugs?These investigations are meant to help to answer open questions concerning the hazard potential posed by nanoparticles of metal oxides for humans. The aim is to fill knowledge gaps about the molecular mechanisms that are following on the oral uptake of iron oxide and zinc oxide nanoparticles.