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

基本信息

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
项目类别：
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

项目摘要

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.

该计划的目标是系统地探索尺寸的物理化学特性的影响，工程纳米材料 (ENM) 的组成、表面不稳定性以及电荷、密度和活性。该项目的目标是确定这些物理/化学特性对 ENM 相互作用的影响与完整的有机体，包括特定的靶器官和靶器官内的特定细胞类型。我们将重点关注 ENM 的主要类别之一，即高纵横比纳米材料 (HARNM)，包括单不同长度的壁碳纳米管（SWNT）和纳米线（NW）。尺寸（直径和长度）和涂层（二氧化硅为例）影响毒性、保留和易位将评估。具有上述不同物理/化学性质的HARNM将被用于一系列吸入/摄入实验后吸收和分布的系统检查。基本的将监测次要靶器官反应，并在模型中监测 HARNM 暴露的影响将评估过敏情况。总体假设是，成分、尺寸、直径和 HARNM 的表面涂层将调节 HARNM 的体内摄取、分布和生物效应大鼠模型。这一假设将通过四个具体目标来解决，这些目标将决定 HARNM 的效果 1）沉积、保留和分布到各个器官； 2）呼吸系统细胞毒性、炎症和气道重塑； 3）呼吸系统氧化应激； 4) ainway 恶化敏感模型中的过度反应。我们将使用跨学科的方法来实现这些目标结合了吸入毒理学、化学、组织病理学、高分辨率成像和新颖的加州大学戴维斯分校开发的方法使我们能够成功解决生物效应这些材料。长期目标是确定这些材料的特征，以降低其毒性和生物效应。相关性（参见说明）；开发和评估技术和方法来评估与相关疾病相关的潜在疾病负担暴露于 ENM。项目 2 的目标是定义高纵横比纳米材料的曝光效应（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反应。