Fabrication of Nanoscale Plastics and Effects on Intestinal Barrier Function In Vitro

项目摘要/摘要 这个被提议的R21计划的首要目标是制造表征良好的纳米塑料(NPs) 由高商品塑料组成，并调查这些纳米颗粒对肠道屏障的影响 在体外发挥作用。这项拟议的研究涉及大量报告，这些报告表明， 饮料和食品含有小规模的碎裂塑料(微塑料或MPS和可能的 NPS)由高商品塑料(例如，聚对苯二甲酸乙二醇酯[PET]、聚酰胺[尼龙]、 高密度和低密度聚乙烯[分别为HDPE和LDPE]、聚丙烯[PP])。但是，当前 关于NPs对生物系统的影响的结论主要是从使用 商用聚苯乙烯(PS)，这并不代表全球主导的广度 塑料制品。不幸的是，从最常见的全球制造的聚合物中提取的NPs是 无法在商业上或通过制造路线获得，从而阻碍了类似于 那些已经用PS完成的手术。该R21计划解决了对科学数据的迫切需求，以 了解非故意摄入NPs对人类健康的风险，这一点已经得到强调 世界卫生组织和欧洲食品安全局。我们将设计和开发 由全球无处不在的塑料组成的具有良好特征的NPs，这些塑料以前没有制造过，或者 以前在哺乳动物细胞或动物模型中进行过测试。我们的设计策略将确保制造的 NP适用于需要示踪剂、紧密的颗粒大小分布、 和刻画得很好的成分。我们的方法将导致使用体外模型进行第一次研究 研究从最常见的高商品塑料中提取的NPs如何影响肠道屏障 功能。最重要的假设是，由全球无处不在的塑料组成的NPs可以与 肠道屏障并影响小肠的屏障功能。我们提出了两个具体的 目标：(1)开发由高商品塑料组成的高度特征化的NPs，适合 评估生物系统和(2)评估NP的消化、转位和对 体外培养小鼠小肠。为了评估NPs对人类健康的风险，需要科学数据，以及 研究消化的NPs对肠道屏障功能的影响是关键的第一步。这款R21 计划是里程碑驱动的，并提供定义的可交付成果，以支持了解步骤如何 非故意摄入NPs会影响人类健康。

PROJECT SUMMARY/ABSTRACT The overarching goal of this proposed R21 program is to fabricate well-characterized nanoplastics (NPs) comprising high-commodity plastics and to investigate the impact of these NPs on intestinal barrier function in vitro. This proposed research addresses the numerous reports showing that drinking water, beverages, and food products contain small-scale fragmented plastics (microplastics or MPs and likely NPs) consisting of high-commodity plastics (e.g., polyethylene terephthalate [PET], polyamide [Nylon], high- and low-density polyethylene [HDPE and LDPE, respectively], polypropylene [PP]). However, current conclusions concerning the effects of NPs on biological systems are primarily deduced from studies using commercially available polystyrene (PS), which does not represent the breadth of globally dominant plastics. Unfortunately, NPs derived from the most common globally manufactured polymers are unavailable, either commercially or via fabrication routes, thereby impeding biological studies similar to those already performed with PS. This R21 program addresses the critical need for scientific data to understand human health risks from the unintentional ingestion of NPs, a need that has been emphasized by both the World Health Organization and European Food Safety Authority. We will design and develop well-characterized NPs comprising globally ubiquitous plastics that have not been fabricated previously or tested in mammalian cells or animal models before. Our design strategy will ensure that the fabricated NPs are appropriate for systematic biological studies that require tracers, tight particle size distributions, and well-characterized compositions. Our approach will result in the first studies using in vitro models to examine how NPs derived from the most common high-commodity plastics affect intestinal barrier function. The overarching hypothesis is that NPs comprising globally ubiquitous plastics can interact with the intestinal barrier and affect the barrier function of the small intestinal tract. We propose two specific aims: (1) develop highly characterized NPs comprising high-commodity plastics that are suitable for assessment in biological systems and (2) evaluate NP digestion, translocation, and interference with the small intestinal tract in vitro. To assess the human health risk of NPs, scientific data are needed, and investigating the impact of digested NPs on intestinal barrier function is a critical first step. This R21 program is milestone-driven and provides defined deliverables to support steps toward understanding how the unintentional ingestion of NPs affects human health.