Cytotoxic effects of surface-modified quantum dots on neuron-like PC12 cells cultured inside microfluidic devices

Abstract

This paper describes the cytotoxic effects of surface-modified quantum dots (QDs) on neuron-like PC12 cells under localized exposure conditions. PC12 cells were cultured and differentiated on a two-compartment microfluidic neuronal device with the aim of preferentially isolating axons from their cell bodies and thus providing localized exposure of cell bodies or axons to QDs. In addition, we used two distinct ligands for surface modification of QDs: mercaptopropionic acid (MPA) and cetyltrimethylammonium bromide/trioctylphosphine oxide (CTAB/TOPO). The results showed that CTAB/TOPO-QDs were toxic to neurons, whereas MPA-QDs were non-toxic. Through general morphological observation, we observed remarkable alterations in the morphology of the neurons induced by CTAB/TOPO-QDs such as cell shrinkage and axonal degeneration. Furthermore, to investigate whether the axonal degeneration was a consequence of neuronal cell death or was due to a direct toxic effect of QDs on axons, preferentially isolated cell bodies and axons were locally exposed to CTAB/TOPO-QDs, followed by an analysis of intracellular reactive oxygen species (ROS) formation and nuclear changes. The results suggested that axonal degeneration could be a consequence of neuronal cell death as well as of direct axonal toxicity. An estimation of the amount of ROS in neurons exposed to CTAB/TOPO-QDs further suggested that oxidative stress could be a leading cause of axonal degeneration and consequent toxicity. In addition, nuclear condensation was observed to be a consequence of QD toxicity.