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CAS-MNP: Elucidating Nanoplastics - Cell Interactions that Enhance Polycyclic Aromatic Hydrocarbon Uptake in an Intestinal Membrane Model

CAS-MNP：阐明纳米塑料 - 增强肠膜模型中多环芳烃吸收的细胞相互作用

基本信息

批准号：
2032376
负责人：
Bjoern Reinhard
金额：
$ 40万
依托单位：
Trustees of Boston University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2032376&HistoricalAwards=false
关键词：
CAS MNP Elucidating Nanoplastics Cell

项目摘要

The large-scale use of plastics has resulted in an accumulation of plastic waste in marine ecosystems, where weathering processes can result in the formation of plastic particles that are small enough to enter the food chain. These small plastic particles are commonly referred to as microplastics or nanoplastics, depending on their exact size. Plastic particles can act as carriers of certain carcinogens, bringing potential risk to the food chain and ultimately to humans. However, the interactions between carcinogens and plastic nanoparticles remain insufficiently understood. This project will address key questions related to the nanoplastics-mediated uptake of carcinogens. The absorption and release of carcinogens from nanoplastics will be investigated in an intestinal model. In synergy with the laboratory work, this project will provide training opportunities in nanotechnology and nanotoxicology. Furthermore, educational web modules on nanoplastics will be developed geared towards a general audience with diverse educational backgrounds. Polycyclic aromatic hydrocarbons are carcinogens that are generated through incomplete combustion processes of organic materials. Human activity has become a major source for polycyclic aromatic hydrocarbons and has resulted in a ubiquitous distribution of these molecules in the environment, including marine ecosystems. Polycyclic aromatic hydrocarbons have a high affinity for plastic nanoparticles due to their hydrophobic character. As plastic nanoparticles, are also accumulated in marine ecosystems, they represent a potential carrier for these carcinogens, which have a poor solubility in water. The sorption and release of polycyclic aromatic hydrocarbons to/from plastic particles depends on a variety of factors, including the chemical nature of the plastics, the size and morphology of the particles, and the pH and chemical composition of the surrounding media. This project will systematically characterize the effect of nanoplastics composition and weathering on the release of polycyclic aromatic hydrocarbons. The experiments will be performed with nanoparticles of different plastics with typical dimensions of 100 nm under well-defined conditions in a simulated gastrointestinal tract model, based on human colon carcinoma cells. Subsequently, the transepithelial transport obtained for free and nanoplastics-associated polycyclic aromatic hydrocarbons will be measured, and the effect of nanoplastics on the intestinal membrane integrity will be determined. By correlating membrane integrity with transmembrane polycyclic aromatic hydrocarbons transport, it will be possible to quantify the effect of nanoparticle-induced membrane damage on polycyclic aromatic hydrocarbons transport. Surface Enhanced Raman Spectroscopy will be applied to detect nanoplastics-induced molecular changes in the cell metabolism that do not lead to an acute change in membrane integrity but can still cause chronic damage. In synergy with the laboratory work, this project will enable substantial educational and training activities. The project will provide training opportunities in nanotechnology and nanotoxicology for at least one PhD student. Furthermore, micro- and nanoplastics have attracted significant public attention, and there is substantial interest in nanoplastics and their interactions with living systems, including humans. This project will develop educational web modules that collate existing information about this theme and disseminate the findings of this research project. These web modules will be geared towards a general audience with diverse educational backgrounds.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

塑料的大规模使用导致塑料废物在海洋生态系统中积累，风化过程可能导致形成足够小的塑料颗粒进入食物链。这些小塑料颗粒通常被称为微塑料或纳米塑料，这取决于它们的确切尺寸。塑料颗粒可以作为某些致癌物质的载体，给食物链乃至人类带来潜在风险。然而，致癌物和塑料纳米颗粒之间的相互作用仍然没有得到充分的了解。该项目将解决与纳米塑料介导的致癌物摄取相关的关键问题。将在肠道模型中研究纳米塑料中致癌物的吸收和释放。在与实验室工作的协同作用下，该项目将提供纳米技术和纳米毒理学方面的培训机会。此外，还将开发面向具有不同教育背景的普通受众的纳米塑料教育网络模块。多环芳烃是通过有机材料的不完全燃烧过程产生的致癌物。人类活动已成为多环芳烃的一个主要来源，并导致这些分子在包括海洋生态系统在内的环境中无处不在。多环芳烃由于其疏水特性而对塑料纳米颗粒具有高亲和力。由于塑料纳米颗粒也在海洋生态系统中积累，它们是这些致癌物的潜在载体，这些致癌物在水中的溶解度很差。塑料颗粒对多环芳烃的吸附和释放取决于多种因素，包括塑料的化学性质、颗粒的大小和形态以及周围介质的pH值和化学成分。该项目将系统地表征纳米塑料成分和风化对多环芳烃释放的影响。这些实验将在基于人结肠癌细胞的模拟胃肠道模型中，在明确定义的条件下，使用典型尺寸为100 nm的不同塑料的纳米颗粒进行。随后，将测量游离和纳米塑料相关多环芳烃的跨上皮转运，并确定纳米塑料对肠膜完整性的影响。通过将膜完整性与跨膜多环芳烃运输相关联，将有可能量化纳米颗粒诱导的膜损伤对多环芳烃运输的影响。表面增强拉曼光谱将用于检测纳米塑料诱导的细胞代谢中的分子变化，这些变化不会导致膜完整性的急性变化，但仍可能导致慢性损伤。该项目与实验室工作协同，将促成实质性的教育和培训活动。该项目将为至少一名博士生提供纳米技术和纳米毒理学方面的培训机会。此外，微塑料和纳米塑料已经引起了公众的极大关注，人们对纳米塑料及其与包括人类在内的生命系统的相互作用产生了浓厚的兴趣。该项目将开发教育网络模块，整理关于这一主题的现有信息，并传播这一研究项目的结果。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。