Effects of nanoparticle dispersion status on bioactivity and translocation in the

描述（由申请人提供）：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压倒性增长，对工人和消费者的健康风险评估是必要的。从毒理学的角度来看，纳米颗粒具有两个促进其毒性的特征。第一个特征涉及纳米颗粒的物理化学特性，其包括纳米颗粒的表面积。第二个特征是纳米颗粒穿越细胞膜的能力。在进行体外或体内研究之前，将纳米颗粒置于液体介质中会极大地影响这两个重要的纳米颗粒特性。然而，纳米颗粒在溶液中聚集，并且聚集状态根据悬浮介质而变化，并且可以影响体外和体内结果。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。将带正电和中性电荷的镍和带负电的氧化铈悬浮在四种不同的分散介质（PBS、DM、Survanta、pluronics）中。为了评估和比较每种悬浮介质如何分散纳米颗粒，将采用各种材料科学表征技术。在表征纳米颗粒/分散介质组合之后，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。将使用小鼠（雄性，C57 BL/6 J，7周龄）进行体内和体外研究。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。还将进行体外研究以分析NLRP 3炎性体在纳米颗粒生物活性中的作用。此外，我们计划使用CytoViva显微镜来评估纳米颗粒的分散状态是否与肺内的颗粒运动相关，以跟踪肺部暴露后给定纳米颗粒的沉积和移位。CytoViva显微镜的使用将为我们提供视觉定位和定量灌注颗粒沉积在肺中的位置（巨噬细胞vs.上皮/间质空间）的能力。本研究提出的问题对纳米技术/毒理学界非常重要。也就是说，高度争论的问题，是否分散状态的纳米粒子悬浮液（暴露前）是重要的，将在拟议的研究中回答。

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.