Project 2: Toxicity of Metallic Nanoparticles and Carbon Nanotubes

项目2：金属纳米颗粒和碳纳米管的毒性

基本信息

批准号：
8900559
负责人：
Agnes B Kane
金额：
$ 0.75万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2015-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8900559
关键词：
Acute Address Aging Amphibole Asbestos Asbestos Basic Science Biochemical Biological Assay Biological Availability Biomedical Research Carbon Carbon Nanotubes Carbon nanoparticle Carcinogens Characteristics Chemicals Complex Complex Mixtures Crocidolite Asbestos Development Disease Drug Formulations Educational Intervention Endocytosis Engineering Environmental Health Environmental Impact Epigenetic Process Epithelial Cells Exposure to Fiber Funding Gene Silencing Geometry Goals Grant Health Heating Human Interdisciplinary Study Ions Iron Laboratories Life Cycle Stages Lung Metals Methods Modeling Modification Molecular Nanotechnology Nickel Occupational Outcome Oxidation-Reduction Oxides Particle Size Pathologist Pathway interactions Process Property Reference Standards Research Research Project Grants Residual state Rhode Island Risk Rodent Sampling Scientist Series Signal Pathway Site Structure-Activity Relationship Superfund Surface Systems Development Techniques Technology Testing Toxic effect Toxicology Transition Elements Tubular formation Universities base biological systems carcinogenesis catalyst chemical property commercialization design exposed human population genotoxicity hypoxia inducible factor 1 innovation interdisciplinary collaboration nanomaterials nanoparticle nanoscale nanotoxicology novel particle physical property prevent programs remediation research study screening sensor wasting

项目摘要

Nanotechnology has great potential for development and application of novel chemical sensors and remediation approaches at Superfund and other toxic waste sites. However, nanomaterials may cause adverse health and environmental impacts during manufacturing, application, and disposal at the end of product life-cycle. A major concern in the emerging field of nanotoxicology is the analogy between commercial and noncommercial asbestos fibers and carbon nanotubes with respect to geometry, aspect ratio, rigidity, surface reactivity, and biopersistence. Identification of the fundamental physicochemical characteristics of nanomaterials relevant for their potential toxicity is required to prevent adverse health effects while retaining their unique properties for environmental sensing and remediation. An interdisciplinary research team at Brown University including a materials scientist, a toxicologic pathologist, and a molecular biologist has developed a panel of amphibole asbestos fibers, metallic nanoparticles, and carbon nanomaterials and innovative approaches for nanotoxicology assays. This panel of model nanomaterials will be expanded to include selected commercial materials subjected to rigorous characterization of toxicologically relevant materials properties. Carbon nanotubes are commercially produced in the presence of metal catalysts including Fe, Ni, or Y alone or in combination. The focus of this SBRP biomedical research project is on nickel-containing nanomaterials. Poorly-soluble nickel compounds are classified as known human carcinogens and nickel nanoparticles are highly toxic in short-term rodent lung toxicity assays. The proposed experiments will focus on the bioavailability and potential toxicity of nickel mobilized from metallic nickel nanoparticles and carbon nanotubes. The biochemical mechanisms responsible for acute toxicity of asproduced or purified commercial carbon nanotube samples will be assessed (Specific Aim 1). The potential synergistic or antagonistic effects of co-exposures to Ni plus Y catalyst residues will be assessed using human lung epithelial cells (Specific Aim 2). Finally, nickel-containing nanomaterials will be tested for activation of epigenetic pathways involved in nickel carcinogenesis (Specific Aims 3 and 4). These experiments will provide mechanistic information that will enable development of manufacturing methods and post processing steps to minimize or mitigate adverse health and environmental impacts of nanomaterials.

纳米技术在新型化学传感器和应用领域具有巨大的开发和应用潜力超级基金和其他有毒废物场的修复方法。然而，纳米材料可能会导致制造、使用和最终处置过程中对健康和环境的不利影响产品生命周期。纳米毒理学新兴领域的一个主要问题是商业毒理学与纳米毒理学之间的类比。以及非商业石棉纤维和碳纳米管的几何形状、长径比、刚性、表面反应性和生物持久性。基本理化特性的鉴定需要与其潜在毒性相关的纳米材料来防止对健康的不利影响，同时保留它们在环境传感和修复方面的独特特性。跨学科研究团队布朗大学包括一名材料科学家、一名毒理学病理学家和一名分子生物学家开发了角闪石石棉纤维、金属纳米粒子和碳纳米材料的面板，纳米毒理学测定的创新方法。该模型纳米材料面板将扩展到包括经过严格毒理学相关表征的选定商业材料材料特性。碳纳米管在金属催化剂存在下进行商业化生产包括单独或组合的Fe、Ni或Y。该 SBRP 生物医学研究项目的重点是含镍纳米材料。难溶性镍化合物被归类为已知的人类在短期啮齿动物肺毒性测定中，致癌物和镍纳米颗粒具有剧毒。拟议的实验将重点关注从金属镍中提取的镍的生物利用度和潜在毒性纳米粒子和碳纳米管。产生的急性毒性的生化机制或纯化的商业碳纳米管样品将被评估（具体目标 1）。潜力将使用人类来评估同时暴露于 Ni 加 Y 催化剂残留物的协同或拮抗作用肺上皮细胞（具体目标 2）。最后，将测试含镍纳米材料的活化作用参与镍致癌的表观遗传途径（具体目标 3 和 4）。这些实验将提供机械信息，促进制造方法和后处理的开发尽量减少或减轻纳米材料对健康和环境的不利影响的步骤。