Assessing the Interaction between Nanomaterials and Biological Systems in vivo to

描述（由申请人提供）：纳米技术的应用正在融入我们的日常生活，但纳米材料的使用安全性仍有待彻底的评估。目前，人们对纳米材料与生物的相互作用知之甚少，为了弥补这一空白，我建议使用胚胎斑马鱼作为快速的体内系统来研究纳米材料在分子水平上的活性。高纯度、配体功能化的银纳米粒子（AgNPs）可以被精确地设计成定制化的物理化学性质。我假设纳米材料的生物活性取决于原始粒径、粒径分布、表面基团的化学组成、表面电荷和团聚状态。为了验证这一假设，我将收集毒性数据，包括发病率和死亡率剂量反应、摄取浓度和纳米颗粒暴露引起的基因表达变化。此外，通过将胚胎斑马鱼暴露于具有高度特异性物理化学特性的银纳米粒子（AgNPs）中，我将确定哪些特性会导致特定的生物效应。所有数据将被记录在纳米材料-生物相互作用（NBI）知识库中。NBI知识库是一个关于纳米材料表征、合成方法和纳米材料-生物相互作用的注释数据仓库，这些数据定义在生物组织的多个层面上。我提交给NBI知识库的数据将有助于基于物理化学性质预测纳米材料暴露的生物效应的关键数据的识别。

DESCRIPTION (provided by applicant): Nanotechnology applications are being incorporated into our daily lives, but the safety of nanomaterials usage still awaits thorough assessment. Currently, little is known about nanomaterial-biological interactions, and to bridge this gap, I propose using embryonic zebrafish as a rapid, in vivo system to investigate the activity of nanomaterials at the molecular level. High-purity, ligand-functionalized silver nanoparticles (AgNPs) can be precisely engineered to custom-manipulate physicochemical properties. I hypothesize that the biological activity of nanomaterials is dependent upon primary particle size, size distribution, chemical composition of surface groups, surface charge and state of agglomeration. To test this hypothesis, I will collect toxicity data including morbidity and mortality dose response, uptake concentration, and nanoparticle exposure-induced changes in gene expression. Additionally, by exposing embryonic zebrafish to silver nanoparticles (AgNPs) engineered to exhibit highly specific physicochemical properties, I will define which properties are responsible for causing specific biological effects. All data will be recorded in the Nanomaterial-Biological Interactions (NBI) knowledge base. The NBI knowledgebase serves as a warehouse for annotated data on nanomaterial characterization, synthesis methods, and nanomaterial-biological interactions defined at multiple levels of biological organization. The data I submit to the NBI knowledgebase will facilitate identification of key data for predicting the biological effects of nanomaterial exposure based on physicochemical properties. PUBLIC HEALTH RELEVANCE: Structure-activity based prediction of health hazard potential of nanomaterials should be in place during technology development. Given that nanomaterials are becoming pervasive, it is imperative that science rapidly develops structure-biological activity relationships for new and emerging classes of nanomaterials. This will serve to both ensure human safety of the technology and minimize the gross inefficiency of blindly developing inappropriate uses of nanomaterials for biomedical and consumer products.