Hippocampal organotypic cultures as ex vivo model for tissue response to upconverting nanoparticles

In the last few years, rare-earth-doped upconverting nanoparticles (UCNPs) have been widely used in different life sciences due to their unique properties. Nanoparticles have become a multifunctional and promising new approach to neurobiological disorders and have shown extraordinary application potential to overcome problems related to conventional treatment strategies. This study evaluated the internalization mechanisms, bio-distribution, and neurotoxicity of NaYF4:20%Yb3+,2%Er3+ UCNPs in rat organotypic hippocampal slices. TEM results showed that UCNPs were easily internalized by hippocampal cells and co-localized with selected organelles inside neurons and astrocytes. Moreover, we found that UCNPs were taken into the neurons via clathrin- and caveolae-mediated endocytosis. Propidium iodide staining and TEM analysis did not confirm the adverse effects of UCNPs on hippocampal slice viability and morphology. Therefore, UCNPs may be a potent tool for bio-imaging and testing new therapeutic strategies for brain diseases in the future.