P30 Yr 2 Pilot- Biodistribution and Impact of Orally Exposed Engineered Nanoparticles on the Function and Homeostasis of Intestinal

Abstract

Background: Exponential growth of nanotechnology offers exciting opportunities to develop nanomedicine, but it also substantially increases risks to the involuntary exposure to potentially toxic materials such as engineered nanoparticles (ENPs). While the health concerns of ENPs have long been acknowledged, the potential health effects of orally exposed ENPs are still poorly understood. Issues related to how dietary ENPs behave in the gastrointestinal tract and whether they will cross the intestinal epithelial barrier and accumulate in other organs remain elusive even though circumstantial evidence suggests that orally exposed ENPs may accumulate in other organs. The interactions of ENPs and intestinal epithelial barrier play a crucial role in the biodistribution of ENPs and their health impacts because the intestinal epithelial lining functions as both a barrier to prevent ENPs and other toxicants from entering into the circulatory system, as well as a primary nutrient absorption site. How the orally exposed ENPs affect the homeostasis of intestinal epithelial lineages is therefore a significant question to investigate and is the primary goal of this project. Using cerium oxide nanoparticles (CeO2NPs) as a model ENP due to its stability, we formulated three aims: (1): Determine the biodistribution of orally exposed CeO2NPs using (single particle) inductively coupled plasma mass spectrometry ((SP)-ICP-MS), (2): Investigate the impact of CeO2NPs on the differentiation/plasticity of intestinal stem cells and (3): Determine the impact of CeO2NPs on the composition of the gut microbiome. The interdisciplinary approach adopted in this pilot study will determine whether the physiology of intestinal stem cells can be directly or indirectly affected by dietary CeO2NPs. This information will shed light on the potential health implications of ENPs in the human food chain and provide insights into the development of nanomedicines