Braakhuis Hedwig M, Giannakou Christina, Peijnenburg Willie J G M, Vermeulen Jolanda, van Loveren Henk, Park Margriet V D Z
a Department of Toxicogenomics , Maastricht University , Maastricht , the Netherlands .
b National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands , and.
Nanotoxicology. 2016 Aug;10(6):770-9. doi: 10.3109/17435390.2015.1127443. Epub 2016 Jan 26.
To study the effects of nanomaterials after inhalation, a large number of in vitro lung models have been reported in literature. Although the in vitro models contribute to the reduction of animal studies, insufficient data exists to determine the predictive value of these in vitro models for the in vivo situation. The aim of this study was to determine the correlation between in vitro and in vivo data by comparing the dose metrics of silver nanoparticles in an in vitro lung model of increasing complexity to our previously published in vivo inhalation study. In vivo, the previously published study showed that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation. The results of the present study show that particle surface area is a suitable dose metric to describe the effects of silver nanoparticles when using a simple monolayer of lung epithelial cells. The dose metric shifted from particle surface area to particle mass when adding an increasing number of macrophages. In addition, a co-culture of endothelial cells, epithelial cells and macrophages on a Transwell® insert correlated less well to the in vivo results compared to the epithelial monolayer. We conclude that for studying the acute pulmonary toxicity of nanoparticles simple in vitro models using an epithelial monolayer better predict the in vivo response compared to complex co-culture models.
为了研究吸入纳米材料后的影响，文献中报道了大量体外肺模型。尽管体外模型有助于减少动物研究，但仍缺乏足够的数据来确定这些体外模型对体内情况的预测价值。本研究的目的是通过比较在一个复杂性不断增加的体外肺模型中银纳米颗粒的剂量指标与我们之前发表的体内吸入研究结果，来确定体外和体内数据之间的相关性。在体内，之前发表的研究表明，以颗粒表面积表示的肺泡剂量是描述吸入后银纳米颗粒毒性的最合适剂量指标。本研究结果表明，当使用简单的肺上皮细胞单层时，颗粒表面积是描述银纳米颗粒效应的合适剂量指标。当添加越来越多的巨噬细胞时，剂量指标从颗粒表面积转变为颗粒质量。此外，与上皮单层相比，在Transwell®小室上进行内皮细胞、上皮细胞和巨噬细胞的共培养与体内结果的相关性较差。我们得出结论，与复杂的共培养模型相比，使用上皮单层的简单体外模型在研究纳米颗粒的急性肺毒性方面能更好地预测体内反应。
