Characterization of Toxicity of Airborne ENMs using Direct in Vitro Exposure

项目摘要 在过去的十年中，工程纳米材料（NM）（人造材料，至少有一个 尺寸< 100 nm）随着它们并入新的或开发中的技术而呈指数增长。 越来越多的行业正在使用这些纳米材料作为防晒霜和化妆品，药物输送系统， 结构材料、半导体和传感器，由于其增强的性能（强度，刚度， 电特性以及化学和生物反应性）。然而，这些有益的特征可 一旦与生物系统接触，也赋予其它有害性质。虽然数量 进入市场的NM每年都在增加，缺乏有关学位的信息， 工人和消费者接触这些纳米材料的条件。 需要一种方法来快速和可靠地评估越来越多的 NM，并以可提供生理学相关毒理学信息的方式进行。我们的项目 通过一种直接暴露于空气-液体界面（ALI）细胞培养物的新方法解决了这一需求， 作为单层和更复杂的文化，以空气中的NM。我们的方法被证明是有效的， 即使在环境现实的条件下，也能在最短的暴露时间内提供结果。这 项目将继续这种方法，提供一个强大的，多功能的和紧凑的设备暴露急性肺损伤细胞 将培养物转化为雾化NM。随着新方法和检测方法的快速发展， 快速评估毒物的生物效应，我们的设备将提供一个新的工具来研究机制， 暴露于空气中的NM可能导致伤害和/或疾病，并提高我们检查和 预测NM的可能作用机制。

Project Summary In the last decade, the use of engineered nanomaterials (NMs) (man-made materials with at least one dimension < 100 nm) has exponentially increased with their incorporation into new or developing technologies. More industries are using these NMs as components of sunscreens and cosmetics, drug delivery systems, structural materials, semiconductors, and sensors, as a result of their enhanced properties (strength, stiffness, electrical characteristics, and chemical and biological reactivity). However, these beneficial characteristics may also confer other detrimental properties once in contact with biological systems. Even though the number of NMs entering the market is increasing every year, there is a lack of information regarding the degree and conditions in which workers and consumers are exposed to these nanomaterials. Needed is a means to rapidly and reliably assess the toxicological properties of the increasing number of NMs, and to do so in a manner that can provide physiologically relevant toxicological information. Our project addresses this need with a novel approach for the direct exposure of air-liquid interface (ALI) cell cultures, both as monolayer and more complex cultures, to airborne NMs. Our approach is shown to be efficient and reproducible, providing results in minimal exposure times, even under environmentally realistic conditions. This project will carry this approach forward to provide a robust, versatile and compact device for exposing ALI cell cultures to aerosolized NMs. Together with rapid development of new methods and assays to cheaply and rapidly asses the biological effects of toxicants, our device will provide a new tool to study the mechanisms by which exposure to airborne NMs may lead to injury and/or disease, and improve our ability to examine and predict possible mechanisms of action of NMs.