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

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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.