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

基本信息

批准号：
8258515
负责人：
Terrance J Kavanagh
金额：
$ 3.01万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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/8258515
关键词：
A/J Mouse Air Antibodies Apoptosis Arsenic Benign Bioinformatics Biological Biological Markers Biology Breathing Budgets Cadmium Carbon Carbon Nanotubes Cell Culture System Cell Line Cell Survival Cell model Cells Characteristics Charge Chemicals Chemistry Chromosome Mapping Complementary DNA Computer software Conceptus Custom Data Development Dose Drug Delivery Systems Educational workshop Elements Embryo Endothelial Cells Engineering Environment Environmental Exposure Epigenetic Process Epithelial Epithelial Cells Epithelium Excretory function Exposure to Female Fluorescent Dyes Gene Expression Genetic Polymorphism Genomics Goals Gold Health Heart Heavy Metals Hepatocyte Histopathology Human Hypersensitivity In Vitro Inbred Mouse Inbred Strains Mice Inflammatory Instruction Journals Kidney Lead Ligands Link Liquid substance Liver Lung Maps Materials Testing Measures Mercury Metabolism Methods Mitochondria Modeling Modification Mouse Strains Mus Nanosphere Nanotubes National Institute of Environmental Health Sciences Nature Necrosis Occupational Oxidation-Reduction Oxidative Stress Pathway Analysis Pathway interactions Phase Poison Protein Engineering Proteins Quantum Dots Reporting Request for Applications Research Rest Risk Risk Assessment Schedule Selenium Semiconductors Services Shapes Signal Pathway Signal Transduction Silver Site Small Interfering RNA Spleen Splenocyte Sports Equipment Staining method Stains Stress Structure Sunscreening Agents Surface Surface Properties System Techniques Technology Tellurium Testing Testis Brain Thymus Gland Tissues Toxic effect Toxicology Transfection Travel Tubular formation Vascular Endothelial Cell Wound Healing Writing absorption aerosolized aqueous base biomineralization cell type ceric oxide chemical property cytokine cytotoxicity design epigenomics genetic technology human tissue imaging modality in vivo in vivo Model insight interest iron oxide kidney epithelial cell lymph nodes macrophage male meetings member metal oxide molecular imaging nanoGold nanocrystal nanofiber nanomaterials nanoparticle nanoparticulate nanorod nanotoxicology optical imaging particle physical property predictive modeling pregnant programs resistant strain response sertoli cell titanium dioxide uptake web page

项目摘要

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 luminexcent 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, hydrophobieity, 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.

工程纳米材料正在或正在被提议用于大量商业领域产品。由于其物理和化学特性高度多样化且尺寸较小，人们担心它们可能对人类健康或环境造成危害。一类重要的 ENM 是量子点 (Qdot)，它是发光半导体纳米晶体由重金属核（例如 CdSe、CdTe、HgTe）组成，帽和涂层结构差异很大，取决于各种应用所需的特性。已知某些特征是纳米颗粒与细胞和组织相互作用的决定因素，包括形状、尺寸、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的性质，尽管如此，还是很难预测它们的毒性。现代基因组学、表观遗传学的进展生物信息学，以及具有充分表征的多态性的多种近交小鼠品系的可用性和调控序列使得绘制和预测许多有毒物质的毒性途径成为可能物质，包括纳米材料。本文提出的研究将利用体外和体内模型气道暴露于雾化量子点纳米粒子 1) 定义物理和化学控制其吸收、分布、代谢、排泄和毒性的特性； 2）使用多个近交系小鼠，绘制与这些特征相关的毒性途径； 3) 纳入从这些体外和体内模型获得的信息转化为风险评估范式，可用于预测纳米材料对人类的毒性。这些信息不仅会定义哪些物理和化学特性对于量子点的不利生物效应很重要，但也会同时推进纳米材料毒理学和功能表观基因组学领域。这些进步然后可以用于纳米材料的安全设计和制造，以最大限度地发挥其对许多人的效用应用程序。