Engineered Nanomaterials: Linking Physical and Chemical Properties to Biology

工程纳米材料：将物理和化学特性与生物学联系起来

• 批准号: 8462273
• 负责人: KENT Ed PINKERTON
• 金额: $ 48.29万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-27 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8462273
• 关键词: Acute; Address; Affect; Asthma; Biological; Biology; Breathing; Caliber; Cell-Mediated Cytolysis; Cells; Charge; Chemistry; Deposition; Engineering; Exposure to; Goals; Histopathology; Hypersensitivity; Image; Inflammation; Inflammatory; Ingestion; Inhalation Toxicology; Investigation; Length; Link; Lung; Lung Inflammation; Measures; Methodology; Modeling; Modification; Monitor; Organ; Organism; Oxidative Stress; Pattern; Positioning Attribute; Principal Investigator; Property; Rattus; Resolution; Respiratory System; Respiratory tract structure; Risk Assessment; Series; Silicon Dioxide; Site; Surface; Techniques; Testing; Toxic effect; Wing; absorption; airway hyperresponsiveness; airway remodeling; arm; burden of illness; cell type; chemical property; cytotoxicity; density; in vitro Model; in vitro testing; in vivo; in vivo Model; insight; macrophage; nanomaterials; nanowire; novel; particle; physical property; programs; research study; response; single walled carbon nanotube; surface coating; uptake

The goal of this program is to systematically explore the influence of physicochemical properties of size, composition, surface lability as well as charge, density, and activity of engineered nanomaterials (ENMs). The goal of this project is to define the effect of these physical/chemical properties on how ENMs interact with the intact organism, including specific target organs and specific cell types within the target organs. We will focus one ofthe major classes of ENMs, the high aspect ratio nanomaterials (HARNMs), including single wall carbon nanotubes (SWNTs) and nanowires (NWs) of various lengths. The importance of size (diameter and length) and coatings (silica as one example) to affect toxicity, retention and translocation will be assessed. HARNM with differing physical/chemical property described above will be employed in a series of systematic examinations of absorption and distribution following inhalation/ingestion experiments. Primary and secondary target organ responses will be monitored, and the influence of HARNM exposure In a model of allergy will be assessed. The overall hypothesis Is that differences in composition, size, diameter and surface coating of HARNMs will modulate the in vivo uptake, distribution and biologic effects of HARNMs in a rat model. This hypothesis will be addressed in four specific aims that will determine the effect of HARNM on 1) deposition, retention and distribution to various organs; 2) respiratory system cytotoxicity, inflammation and airway remodeling; 3) oxidative stress in the respiratory system; and 4) exacerbation of ainway hyperresposiveness in a sensitive model. We will address these aims using a transdisciplinary approach that combines inhalation toxicology, chemistry, histopathology, high resolution imaging and novel methodologies developed at UC Davis that uniquely position us to successfully address the biological effects of these materials. The long term goal is to identify features of these materials that reduce their toxicity and biological effects. RELEVANCE (See instnjctions); To develop and evaluate techniques and approaches to assess the potential disease burden associated with exposures to ENMs. The goal of Project 2 is to define exposure effects of high aspect ratio nanomaterials (single walled carbon nanotubes and nanowires) in an in vivo inhalation model that includes airways hyperresonsiveness.

该程序的目的是系统地探索大小的物理化学特性的影响， 工程纳米材料（ENM）的组成，表面不稳定以及电荷，密度和活性。 该项目的目的是定义这些物理/化学特性对ENM相互作用的影响 完整的生物体，包括特定的靶器官和目标器官内的特定细胞类型。我们 将集中于主要类ENM的一类 壁碳纳米管（SWNT）和各个长度的纳米线（NWS）。大小的重要性（直径 以及长度）和涂层（二氧化硅作为一个例子），以影响毒性，保留和易位将是 评估。上述物理/化学特性不同的Harnm将在一系列 吸入/摄入实验后的吸收和分布的系统检查。基本的 将监控次要目标器官的响应，并在模型中受到Harnm暴露的影响 将评估过敏。总体假设是组成，大小，直径和 Harnms的表面涂层会调节A Harnms的体内摄取，分布和生物学作用 大鼠模型。该假设将以四个具体目标来解决，以决定Harnm的影响 1）沉积，保留和分配到各种器官； 2）呼吸系统细胞毒性，炎症 和气道重塑； 3）呼吸系统中的氧化应激； 4）加剧Ainway 敏感模型中的高响应性。我们将使用跨学科方法来解决这些目标 结合吸入毒理学，化学，组织病理学，高分辨率成像和新颖 加州大学戴维斯分校开发的方法论，它独特地定位了我们成功解决生物学效应的方法 这些材料。长期目标是确定这些材料的特征，以降低其毒性和 生物学效应。 相关性（请参阅Instnjctions）； 开发和评估技术和方法，以评估与 接触ENM。项目2的目的是确定高纵横比纳米材料的暴露效果 （单壁碳纳米管和纳米线）在包括气道的体内吸入模型中 过度度量。