Linking the physical and chemical characteristics of Qdots to their toxicity

将 Qdot 的物理和化学特性与其毒性联系起来

• 批准号: 8464705
• 负责人: Terrance J Kavanagh
• 金额: $ 106.21万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-24 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8464705
• 关键词: A/J Mouse; Air; Apoptosis; Arsenic; Benign; Bioinformatics; Biological; Biological Markers; Biology; Breathing; Cadmium; Carbon; Carbon Nanotubes; Cell Culture System; Cell Line; Cell Survival; Cell model; Cells; Characteristics; Charge; Chemicals; Chromosome Mapping; Complementary DNA; Computer software; Conceptus; Custom; Data; Development; Dose; Elements; Embryo; Endothelial Cells; Engineering; Environment; Environmental Exposure; Epigenetic Process; Epithelial; Epithelial Cells; Epithelium; Excretory function; Exposure to; Female; Fluorescent Dyes; Gene Expression Profiling; Genetic Polymorphism; Genomics; Goals; Gold; Health; Heart; Heavy Metals; Hepatocyte; Histopathology; Human; Hydrophobicity; Hypersensitivity; In Vitro; Inbred Mouse; Inbred Strains Mice; Inflammatory; Kidney; Lead; Link; Liquid substance; Liver; Lung; Maps; Materials Testing; Measures; Mercury; Metabolism; Methods; Mitochondria; Modeling; Mus; Nanosphere; Nanotubes; National Institute of Environmental Health Sciences; Nature; Necrosis; Occupational; Oxidation-Reduction; Oxidative Stress; Pathway Analysis; Pathway interactions; Phase; Poison; Proteins; Quantum Dots; Request for Applications; Research; Risk; Risk Assessment; Selenium; Semiconductors; Shapes; Signal Pathway; Signal Transduction; Silver; Site; Small Interfering RNA; Spleen; Splenocyte; Sports Equipment; Stress; Structure; Sunscreening Agents; Surface; Surface Properties; System; Techniques; Tellurium; Testing; Testis Brain; Thymus Gland; Tissues; Toxic effect; Toxicology; Transfection; Tubular formation; Vascular Endothelial Cell; Wound Healing; absorption; aerosolized; base; cell type; ceric oxide; chemical property; cytokine; cytotoxicity; deep sequencing; design; epigenomics; genetic technology; human tissue; imaging modality; in vivo; in vivo Model; insight; interest; iron oxide; kidney epithelial cell; lymph nodes; macrophage; male; member; metal oxide; nanoGold; nanocrystal; nanofiber; nanomaterials; nanoparticle; nanoparticulate; nanorod; nanosilver; optical imaging; particle; physical property; predictive modeling; pregnant; programs; resistant strain; response; sertoli cell; titanium dioxide; uptake

DESCRIPTION (provided by applicant): Engineered nanomaterials are being used or are being proposed for use in a large number of commercial products. Because of their highly diverse physical and chemical characteristics, and their small size, concerns have been raised regarding their potential to cause harm to human health or the environment. One important class of ENMs are quantum dots (Qdots) which are luminescent semiconductor nanocrystals composed of heavy metal cores (e.g. CdSe, CdTe, HgTe) with cap and coating structures that vary greatly, depending upon the characteristics required for various applications. Certain characteristics are known to be determinants for the interaction of nanoparticles with cells and tissues, including shape, size, hydrophobicity, and surface charge. Because of the highly variable nature of these and other engineered nanomaterials, it will be nonetheless difficult to predict their toxicity. Modern advances in genomics, epigenetics and bioinformatics, and the availability of multiple strains of inbred mice with well characterized polymorphisms and regulatory sequences have made it possible to map and predict toxicity pathways for many toxic substances including nanomaterials. The research proposed herein will utilize in vitro and in vivo models of airway exposure to aerosolized quantum dot nanoparticles to 1) define the physical and chemical characteristics that govern their absorption, distribution, metabolism, excretion and toxicity; 2) using multiple inbred strains of mice, map toxicity pathways associated with these characteristics; and 3) incorporate the information that is obtained from these in vitro and in vivo models into a risk assessment paradigm that will be used to predict nanomaterial toxicity to humans. Such information will not only define which physical and chemical characteristics are important for the adverse biological effects of quantum dots, but will also simultaneously advance the fields of nanomaterial toxicology and functional epigenomics. These advances can then be used in safe design and manufacturing of nanomaterials so as to maximize their utility for many applications.

描述(申请人提供)：工程纳米材料正在使用或正在被提议用于大量商业产品。由于其高度不同的物理和化学特性，以及它们的体积小，人们对它们可能对人类健康或环境造成损害表示关注。量子点(Qdots)是一类重要的纳米发光材料，它是由重金属核(如CdSe、CdTe、HgTe)组成的发光半导体纳米晶体，具有不同的帽和涂层结构，根据不同应用所需的特性而变化很大。已知某些特征是纳米粒子与细胞和组织相互作用的决定因素，包括形状、大小、疏水性和表面电荷。由于这些和其他工程纳米材料的高度可变性质，仍然很难预测它们的毒性。基因组学、表观遗传学和生物信息学的现代进展，以及具有良好多态和调控序列的多品系近交系小鼠的出现，使得绘制和预测包括纳米材料在内的许多有毒物质的毒性途径成为可能。本文提出的研究将利用雾化量子点纳米颗粒的体外和体内呼吸道暴露模型来1)确定支配其吸收、分布、新陈代谢、排泄和毒性的物理和化学特征；2)使用多个近交系小鼠，绘制与这些特征相关的毒性路径；3)将从这些体外和体内模型中获得的信息纳入风险评估范式，用于预测纳米材料对人类的毒性。这些信息不仅将确定哪些物理和化学特性对量子点的不利生物效应是重要的，而且还将同时推动纳米材料毒理学和功能表观基因组学领域的发展。这些进展可以用于纳米材料的安全设计和制造，从而最大限度地提高其在许多应用中的效用。