EAGER: Low-level detection of complex nanomaterials in biological media.

grulke, Eric a.该项目将侧重于应用加速器质谱法（AMS）进行生物介质中复杂纳米材料的低水平检测的概念验证研究。一个成功的项目将使在环境、健康和安全研究中对复杂工程纳米材料（enm作为纳米粒子）的命运和运输的机理研究取得重大进展。AMS对稀有同位素的分离具有高选择性和高灵敏度。在本提案中，复杂enm被定义为以一种材料为核心的纳米颗粒和不同的表面结合分子（以下称为涂层），以帮助其在应用中的性能。在环境和生物测试过程中，复杂的ENM纳米颗粒经常聚集在一起，核心和涂层都可能被这种暴露所改变，并且需要对核心和涂层材料进行材料平衡，以便正确解释它们在产品生命周期中的运输和转化。该研究小组最近在核心和涂层中合成了含有不同稀有同位素的复杂ENMs。提出了两种途径：1)合成和测试一个复杂的ENM系统，一个26al标记的氧化铝核心（Al2O3）和14c标记的涂层（柠檬酸），将在大鼠模型中进行低剂量测试；2)合成和生物降解评估核心材料，32si标记的介孔二氧化硅和涂层材料，14c标记的PLGA。途径1的工作将试图证明AMS方法的检测下限，预计其灵敏度是放射性检测的103到109倍。途径2的工作将为可降解岩心和涂层的明确测试提供一个实验系统。由于这些稀有同位素（RI）可以使用AMS在原子水平附近检测到，因此应该可以识别在给药、细胞摄取、环境化学品涂层、细胞或环境中的转化过程中摩尔比（涂层RI/ENM RI）的任何变化。转换测试将在另一个后续项目中进行。智力优势：研究成功将开发出一种高灵敏度和高选择性的稀有同位素AMS方法，作为测量相关介质中复杂ENM转化的平台技术。AMS在确定生物和环境介质中复杂enm的长期命运方面尤其有价值，特别是在enm聚集或聚集的情况下。这些测试系统将满足NNI 2011 EHS研究战略需求报告中规定的ENM测量基础设施需求。更广泛的影响：一个成功的提案将刺激和支持下一代仪器和多用户设施的发展和传播，特别是AMS方法在纳米材料毒理学的EHS研究中的应用。研究人员将继续他们目前的教育和培训活动，并将包括EGR 780的新方法，医学应用纳米材料的表征，这是一个支持我们的癌症纳米技术培训中心的新课程，一个26al标记的nih资助项目。

AbstractCBET- 1249123Grulke, Eric A.This project will focus on proof-of-concept research applying Accelerator Mass Spectrometry (AMS) for low-level detection of complex nanomaterials in biological media. A successful project will enable major improvements in mechanistic studies of the fate and transport of complex engineered nanomaterials (ENMs as nanoparticles) in environmental, health and safety studies. AMS can separate rare isotopes with high selectivity and high sensitivity. In this proposal, complex ENMs are defined as nanoparticles with one material as their core and different surface-bound molecules (hereafter referred to as coatings) to assist their performance in applications. Complex ENM nanoparticles often agglomerate during environmental and biological testing, both the core and coating may be transformed by such exposures, and material balances need to be performed on both the core and coatings materials in order to properly interpret their transport and transformations over the product life cycles.The research team has recently synthesized complex ENMs containing different rare isotopes in the core and the coating. Two pathways are proposed: 1) the synthesis and testing of a complex ENM system, an 26Al-labeled alumina core (Al2O3) with 14C-labeled coatings (citric acid), which will be tested at low dose levels in a rat model and 2) the synthesis and biodegradation evaluation of both a core material, 32Si-labeled mesoporous silica, and a coating material, 14C-labeled PLGA. Pathway 1 work will attempt to demonstrate the lower limits of detection of the AMS method, which is expected to be 103 to 109 times more sensitive that radioactivity detection. Pathway 2 work will provide an experimental system for explicit testing of degradable cores and coatings. As these rare isotopes (RI) can be detected near attomole levels using AMS, it should be possible to identify any changes in the molar ratios (coating RI/ENM RI) during dosing, cell uptake, coating by environmental chemicals, transformations in cell, or in the environment. Transformational testing will be done in another, follow-on, project.Intellectual Merit:A successful study will develop rare isotope AMS, a method with high sensitivity and high selectivity, as a platform technology for measurement of complex ENM transformations in relevant media. AMS should be particularly valuable in determining the long-term fate of complex ENMs in biological and environmental media, especially if the ENMs are aggregated or agglomerated. These test systems will address ENM measurement infrastructure needs specified in the NNI 2011 EHS Research Strategy Needs report.Broader Impact:A successful proposal will stimulate and support the development and dissemination of next-generation instrumentation and multiuser facilities, specifically, the application of AMS methods to EHS studies of nanomaterial toxicology. The investigators will continue their current activities in education and training, and will include the new methodology in EGR 780, Characterization of nanomaterials for medical applications, is a new course supporting our Cancer Nanotechnology Training Center, an 26Al-labeled NIH-funded program.