The role of mitochondria in nanoparticle-specific stem cell toxicity

Abstract

proliferation at 10-50 µg/ml and 100-250 µg/ml respectively, depending on the duration of exposure. COOH-PS NPs did not significantly affect cell viability at the concentrations tested (up to 250 µg/ml), but interfered with cellular metabolism. PVP-Ag and TiO2 NPs strongly affected cell cycle dynamics, although particle-specific effects were osberved in cell proliferation and cell cycle phase distributions. Responses depended on exposure conditions, again empasizing the importance of studying the interaction between physicolochemical characterization, uptake and effects. Underlying these changes, NP exposure induced mitochondrial swelling, membrane depolarization and network structure alterations as determined by TEM, JC-10 assay and Mitotracker CMXRos Red imaging, respectively. Furthermore, absence of endoplasmic reticulum dilations and presence of lipid droplets were detected via TEM after 48 h exposure to PVP-Ag and TiO 2 NPs. Our preliminary results suggest that TiO 2 NPs and mostly PVP-Ag NPs harm stem cell functioning while COOH-PS NPs showed less adverse effects at the cell cycle level. The detected subcellular changes were different for different particles, showing the increasing need of comparing different particle types, in relation to their physicochemical characteristics. For the tested exposures, we hypothesise that mito-chondria operate as a signalling hub, guiding the activation of downstream transcriptional processes and stem cell dynamics.