Comparative study of nanoparticle uptake and impact in murine lung, liver and kidney tissue slices

To determine responses to nanoparticles in a more comprehensive way, current efforts in nanosafety aim at combining the analysis of multiple endpoints and comparing outcomes in different models. To this end, here we used tissue slices from mice as 3Dex vivomodels and performed for the first time a comparative study of uptake and impact in liver, lung, and kidney slices exposed under the same conditions to silica, carboxylated and amino-modified polystyrene. In all organs, only exposure to amino-modified polystyrene induced toxicity, with stronger effects in kidneys and lungs. Uptake and distribution studies by confocal microscopy confirmed nanoparticle uptake in all slices, and, in line with what observedin vivo,preferential accumulation in the macrophages. However, uptake levels in kidneys were minimal, despite the strong impact observed when exposed to the amino-modified polystyrene. On the contrary, nanoparticle uptake and accumulation in macrophages were particularly evident in lung slices. Thus, tissue digestion was used to recover all cells from lung slices at different exposure times and to determine by flow cytometry detailed uptake kinetics in lung macrophages and all other cells, confirming higher uptake by the macrophages. Finally, the expression levels of a panel of targets involved in inflammation and macrophage polarization were measured to determine potential effects induced in lung and liver tissue. Overall, this comparative study allowed us to determine uptake and impact of nanoparticles in real tissue and identify important differences in outcomes in the organs in which nanoparticles distribute.