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.
This study will examine how the dispersion status of nanoparticles correlates with both the in vitro and in vivo bioactivity/toxicity of the particle. Furthermore, this study will also assess how the deposition and movement of the nanoparticle in the lung could be dependent upon both the dispersion media used as well as the degree of dispersion of the nanoparticle solution.
|Sager, Tina; Wolfarth, Michael; Keane, Michael et al. (2016) Effects of nickel-oxide nanoparticle pre-exposure dispersion status on bioactivity in the mouse lung. Nanotoxicology 10:151-61|
|Sager, Tina M; Wolfarth, Michael; Leonard, Stephen S et al. (2016) Role of engineered metal oxide nanoparticle agglomeration in reactive oxygen species generation and cathepsin B release in NLRP3 inflammasome activation and pulmonary toxicity. Inhal Toxicol 28:686-697|