UNS:Novel probes to quantify the relative importance of ion and particle uptake when assessing nanoparticle bioavailability

#1508931铅，杰米纳米粒子可能是一种重要的环境污染物，因为它们的使用导致排放到环境中，其中许多已被证明是有毒的。要产生毒性，纳米粒子必须进入细菌或鱼等生物体。这种“生物利用度”是由从环境中吸收、从生物体中流失和其他过程决定的。然而，尚不清楚这些过程是直接与粒子一起发生，还是粒子溶解后产生离子并被生物体吸收。该项目将开发新的纳米颗粒，可以直接区分离子和纳米颗粒的生物利用度过程；一旦开发出来，纳米粒子将用于环境生物，如贝类，以回答这个问题：纳米粒子的生物利用度是由粒子吸收还是离子吸收控制的？结果将是更好地理解纳米生物利用度作为纳米毒性的前兆。这一建议将有助于了解生物利用度和生物积累的机制，作为毒性的前兆；特别是，实验和模型研究将允许对以下问题给出明确的答案：纳米颗粒的生物利用度是由颗粒特定摄取（和损失）还是由溶解后的离子摄取控制的？此外，将编制一套工具，分发给研究界，使基本生物过程和危害程度的问题能够更广泛地针对一系列生物体和条件得到回答。提出的研究将开发一个新粒子库，它是三层核壳材料，在核心和外壳中用不同的稳定同位素进行同位素标记，由一个不溶的中心层分开。这些受到严格约束和完全表征的纳米颗粒将被用作探针，对模式生物进行范围研究，以回答与颗粒或离子生物积累相关的基本问题。还将研究离子和粒子在生物吸收和消除机制、食物和水生暴露中的相对重要性以及溶液化学的重要性。所开发的纳米颗粒（正在申请专利）和毒性研究直接促进了一个安全和可持续的产业的发展，这将具有普遍的社会效益。两名博士生将接受跨学科领域的培训，涉及合成化学、计量学和毒理学。学生将获得在学术和政府实验室工作的经验。该项目的产出将被纳入环境纳米科学与风险中心（CENR）的教学中，学生们将作为一项培训活动来帮助这项工作。中央研究中心聘请了一名博士后专门协助外联工作，我们将采取具体的传播措施，向公众和学生群体传播项目的科学和技术进展。

#1508931Lead, JamieNanoparticles may be an important environmental contaminant because their use leads to discharge into the environment and many of them have been shown to be toxic. In order to be toxic, nanoparticles must enter an organism such as a bacterium or a fish. This "bioavailability" is governed by the uptake from the environment, loss from the organism and other processes. However, it is not known if these processes occur directly with the particle or if the particle dissolves to give ions and the ions are taken into an organism. This project will develop new nanoparticles which can distinguish directly between ion and nanoparticle bioavailability processes; once developed the nanoparticles will be used on environmental organisms such as shellfish to answer the question: is nanoparticle bioavailability controlled by particle or ion uptake? The outcome will be a better understanding of nano-bioavailability as a precursor to nanotoxicity.This proposal will help to understand the mechanisms of bioavailability and bioaccumulation, as a precursor to toxicity; in particular, experimental and modelling studies will allow definitive answers to be generated on the question: is nanoparticle bioavailability controlled by particle specific uptake (and loss) or by ion uptake after dissolution. In addition, a set of tools will be produced, which will be disseminated to the research community, which will enable these questions of fundamental biological processes and hazard levels to be answered more broadly for a range or organisms and conditions. The proposed research will develop a library of novel particles, which are three layer core-shell materials, isotopically labelled with different stable isotopes in the core and outer shell, separated by an insoluble central layer. The tightly constrained and fully characterized nanoparticles will then be used as probes to perform scoping studies on model organisms to answer fundamental questions related particle or ion bioaccumulation. The relative importance of the ion and particle in biouptake and elimination mechanisms, in food and aquatic exposures and the importance of solution chemistry will also be investigated.The developed nanoparticle (patent pending) and the study of toxicity feed directly into the development of a safe and sustainable industry, which will be of general societal benefit. Two doctoral students will be trained in interdisciplinary areas involving synthetic chemistry, metrology and toxicology. The students will be given experience in both academic and government laboratories. The outputs of the project will be incorporated into teaching performed at the Center for Environmental Nanoscience and Risk (CENR) and the students will help in this as a training exercise. The CENR employs a postdoctoral fellow to specifically aid in outreach and we will pursue specific dissemination measures to reach the public and the student body and inform them of the projects scientific and technological advances.