NIRT: Understanding Robust Large Scale Manufacturing of Nanoparticles and Their Toxicology

NIRT：了解纳米颗粒的稳健大规模制造及其毒理学

• 批准号: 0506968
• 负责人: Mitchell Smooke
• 金额: $ 140万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0506968&HistoricalAwards=false
• 关键词: NIRT; Understanding; Robust; Large; Scale

This proposal was received in response to Nanoscale Science and Engineering initiative, NSF 04-043, category NIRT. The proposed study will develop the fundamental understanding needed to manufacture well controlled and characterized, elemental carbon-based nanoparticles, which are likely the materials to which human beings are most frequently exposed. The study will employ a specialized reactor to generate engineered nanoparticles in collaboration with the world's largest manufacturer of nanoparticles, who will also evaluate the particles for actual application as tire reinforcements and in conductive polymers. The studies will employ and develop state-of-the-art, real-time particle characterization methods, including quantitative single-particle mass spectrometry, as well as particle characterization that bridges the gap between the molecular and particulate scales. Process models that include detailed chemistry coupled to aerosol dynamics will be developed as a predictive tool to provide detailed information on both microstructure and composition. A particularly attractive feature of the project is its inclusion of an extensive effort in toxicology. Mechanisms of particle-cell interactions will be evaluated and potential adverse/beneficial effects will be determined using a tiered testing approach. At first, in vitro studies will be performed using specific target cells (lung epithelial, vascular endothelial, neurons and others) to evaluate the oxidative stress inducing potential of the engineered nanoparticles. This will be followed by in vivo studies in rats with delivery of the particles to the circulation and to the lung, followed by evaluation of potential adverse pulmonary and systemic effects. The proposed work combines an outstanding capability to manipulate and characterize nanoparticle structure, morphology, and chemistry with an industrial firm willing to evaluate their performance in multibillion-dollar applications, and a team of medical researchers performing fundamental studies on the degrees and mechanisms of their toxicity. As such, the study addresses current key issues concerning both the commercial and societal impacts of nanotechnology.

该提案是响应纳米科学与工程倡议，NSF 04-043，类别NIRT。 这项拟议的研究将发展制造良好控制和表征的元素碳基纳米颗粒所需的基本理解，这些纳米颗粒可能是人类最经常接触的材料。 该研究将采用专门的反应器与世界上最大的纳米颗粒制造商合作生产工程纳米颗粒，后者还将评估颗粒作为轮胎增强材料和导电聚合物的实际应用。这些研究将采用和开发最先进的实时颗粒表征方法，包括定量单颗粒质谱法，以及弥合分子和颗粒尺度之间差距的颗粒表征。将开发包括与气溶胶动力学耦合的详细化学过程模型，作为预测工具，以提供微观结构和成分的详细信息。 该项目的一个特别吸引人的特点是它包括了毒理学方面的广泛努力。 将评价颗粒-细胞相互作用的机制，并使用分层试验方法确定潜在的不良/有益作用。首先，将使用特定的靶细胞（肺上皮细胞、血管内皮细胞、神经元等）进行体外研究，以评估工程化纳米颗粒的氧化应激诱导潜力。随后将进行大鼠体内研究，将颗粒输送至循环和肺部，然后评价潜在的肺部和全身不良反应。拟议的工作结合了操纵和表征纳米颗粒结构，形态和化学的杰出能力，一家工业公司愿意评估其在数十亿美元应用中的性能，以及一组医学研究人员对其毒性程度和机制进行基础研究。 因此，这项研究解决了当前有关纳米技术的商业和社会影响的关键问题。