Effects of nanoparticle dispersion status on bioactivity and translocation in the

描述(申请人提供)：纳米技术正在成为世界上最有前途的新技术之一。由于纳米技术领域的巨大增长，对工人和消费者的健康风险评估都是必要的。从毒理学的角度来看，纳米颗粒具有两个增强其毒性的特征。第一个特征涉及纳米颗粒的物理化学特性，包括纳米颗粒的表面积。第二个特征是纳米粒子穿过细胞膜的能力。在进行体外或体内研究之前，将纳米颗粒放置在液体介质中对这两个重要的纳米颗粒特性有很大影响。然而，纳米颗粒在溶液中团聚，团聚状态随悬浮介质的不同而不同，会影响体外和体内的结果。我们假设纳米颗粒的分散状态将与颗粒的生物活性/毒性相关。此外，纳米颗粒在肺中的沉积和移动将取决于所使用的分散介质以及纳米颗粒溶液的分散程度。带正电荷和带中性电荷的镍和带负电荷的氧化铈将悬浮在四种不同的分散介质中(PBS、DM、Survanta、Multionics)。为了评估和比较每种悬浮介质如何分散纳米颗粒，将使用各种材料科学表征技术。在确定纳米颗粒/分散介质组合的特征之后，我们将评估分散状态是否与纳米颗粒的体外和体内生物活性相关。体内和体外研究都将使用小鼠(雄性，C57BL/6J，7周大)。对给定纳米颗粒的炎症和组织病理学反应将作为时间的函数进行评估。体外研究也将分析NLRP3炎性小体在纳米颗粒生物活性中的作用。此外，我们计划使用Cytoviva显微镜来跟踪给定纳米颗粒在肺部暴露后的沉积和移位，以评估纳米颗粒的分散状态是否与颗粒在肺内的运动有关。Cytoviva显微镜的使用将使我们能够直观地定位和量化注入的颗粒在肺内沉积的位置(巨噬细胞与上皮/间质间隙)。这项研究提出的问题对纳米技术/毒理学领域非常重要。也就是说，纳米颗粒悬浮液的分散状态(暴露前)是否重要这一备受争议的问题将在拟议的研究中得到回答。

DESCRIPTION (provided by applicant): Nanotechnology is emerging as one of the world's most promising new technologies. Due to the overwhelming growth of the nanotechnology field, health risk assessment for both workers and consumers is warranted. From a toxicology perspective, nanoparticles possess two features that promote their toxicity. The first feature involves physical-chemical characteristics of the nanoparticle, which include the surface area of the nanoparticle. The second feature is the ability of the nanoparticle to traverse cell membranes. These two important nanoparticle characteristics are greatly influenced by placing nanoparticles in liquid medium prior to conducting in vitro or in vivo studies. However, nanoparticles agglomerate in solution and the agglomeration status varies depending on the suspension medium and can affect both in vitro and in vivo results. We hypothesize that the nanoparticle dispersion status will correlate with the bioactivity/toxicity of the particle. Furthermore, the deposition and movement of the nanoparticle in the lung will be dependent upon both the dispersion media used as well as the degree of dispersion of the nanoparticle solution. Positively and neutrally charged nickel and negatively charged cerium oxide will be suspended in four different dispersion media (PBS, DM, Survanta, pluronics). To assess and compare how each suspension media dispersed the nanoparticles, a variety of material science characterization techniques will be employed. After characterizing the nanoparticle/dispersion media combinations we will assess whether dispersion status correlates with the in vitro and in vivo bioactivity of the nanoparticle. Both in vivo and in vitro studies will be conducted using mic (male, C57BL/6J, 7 weeks old). The inflammatory and histopathologic response to the given nanoparticles will be assessed as a function of time. In vitro studies will also be conducted to analyze the role of the NLRP3 inflammasome in nanoparticle bioactivity. Furthermore, we plan to assess whether dispersion status of the nanoparticle correlates with particle movement within the lung using CytoViva microscopy to track the deposition and translocation of the given nanoparticles after pulmonary exposure. The utilization of the CytoViva microscope will provide us with capabilities to visually locate and quantify where the instilled particles have deposited i the lung (macrophages vs. epithelium/interstitial space). The proposed questions of this study are of great importance to the nanotechnology/toxicology community. Namely the highly debated question of whether dispersion status of the nanoparticle suspension (pre-exposure) is of importance, will be answered in the proposed studies.