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

该提案是响应纳米尺度科学与工程计划，NSF 04-043，类别NIRT而收到的。拟议的研究将发展基本的理解，需要制造良好控制和表征，元素碳基纳米粒子，这可能是人类最经常接触的材料。这项研究将与世界上最大的纳米颗粒制造商合作，使用一个专门的反应器来产生工程纳米颗粒，后者还将评估这些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，以及弥合分子和颗粒尺度之间差距的颗粒表征。过程模型将包括与气溶胶动力学相耦合的详细化学过程，作为一种预测工具，提供有关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在毒理学方面进行了广泛的努力。将评估颗粒-细胞相互作用的机制，并使用分层测试方法确定潜在的不利/有益影响。首先，将使用特定靶细胞（肺上皮细胞、血管内皮细胞、神经元细胞等）进行体外研究，以评估工程纳米颗粒诱导氧化应激的潜力。随后将在大鼠体内进行研究，将颗粒输送到循环系统和肺部，然后评估潜在的不良肺部和全身影响。提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，以及愿意在数十亿美元的应用中评估其性能的工业公司，以及对其毒性程度和机制进行基础研究的医学研究团队。因此，该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。

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.