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.

这个项目的目标是系统地探索尺寸的物理化学性质的影响， 工程纳米材料(ENM)的组成、表面稳定性以及电荷、密度和活性。 该项目的目标是定义这些物理/化学属性对ENM如何相互作用的影响 与完整的生物体，包括特定的目标器官和目标器官内的特定细胞类型。我们 将重点关注主要类别之一的ENM，即高深宽比纳米材料(HARNm)，包括单一 不同长度的壁碳纳米管(SWNTs)和纳米线(NW)。尺寸(直径)的重要性 和长度)和涂层(例如二氧化硅)会影响毒性、保留和移位 评估过了。具有上述不同物理/化学性质的HARNM将用于一系列 吸入/摄取实验后对吸收和分布的系统检查。主要 并将监测次级靶器官反应，以及HARNM暴露对模型的影响 过敏症的发生率将会被评估。总体假设是，成分、大小、直径和 HARNms的表面包覆将调节HARNms在小鼠体内的摄取、分布和生物学效应 大鼠模型。这一假设将在决定HARNM效果的四个具体目标中得到解决 1)沉积、滞留和分布于各器官；2)呼吸系统细胞毒性、炎症 和呼吸道重塑；3)呼吸系统的氧化应激；以及4)主动脉的恶化 敏感模型中的高反应性。我们将使用跨学科的方法来解决这些目标 它结合了吸入毒理学、化学、组织病理学、高分辨率成像和新技术 加州大学戴维斯分校开发的方法使我们能够成功地解决生物效应 这些材料的一部分。长期目标是确定这些材料的特性，以降低它们的毒性和 生物效应。 相关性(见实例)； 开发和评估评估潜在疾病负担的技术和方法 暴露于新城疫。项目2的目标是定义高纵横比纳米材料的曝光效果 (单壁碳纳米管和纳米线)在包括呼吸道的体内吸入模型中 超强共鸣。