Engineered Nanomaterials: Linking Physical and Chemical Properties to Biology

该项目的目标是系统地探索尺寸的物理化学性质的影响， 组成、表面不稳定性以及电荷、密度和工程纳米材料（ENM）的活性。 本项目的目标是确定这些物理/化学性质对ENM如何相互作用的影响 与完整的生物体，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，高纵横比纳米材料（HARNM），包括单 壁碳纳米管（SWNT）和各种长度的纳米线（NW）。尺寸（直径）的重要性 和长度）和涂层（二氧化硅作为一个实例）来影响毒性、保留和移位， 评估。具有上述不同物理/化学性质的HARNM将被用于一系列的制备方法中。 在吸入/摄入实验后对吸收和分布进行系统检查。初级 和次级靶器官反应，以及模型中HARNM暴露的影响 过敏反应将被评估。总的假设是，成分、大小、直径和 HARNM的表面涂层将调节HARNM在体内的摄取、分布和生物效应， 大鼠模型这一假设将在确定HARNM效果的四个具体目标中得到解决 1）沉积、滞留和分布到各种器官; 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;和4）气道炎症的恶化。 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 它结合了吸入毒理学、化学、组织病理学、高分辨率成像和新颖的 在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。长期目标是确定这些材料的特性，以降低其毒性， 生物效应。 相关性（见说明）; 开发和评估评估与以下疾病相关的潜在疾病负担的技术和方法： 暴露于ENM。项目2的目标是确定高纵横比纳米材料的暴露效应 （单壁碳纳米管和纳米线）在包括气道的体内吸入模型中的作用。 过度共鸣

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.