Multiwalled carbon nanotubes inhibit fluorescein extrusion and reduce plasma membrane potential in in vitro human glioma cells.

In the study on the interactions of carbon nanotubes with living cells, the cell membrane deserves particular attention as it provides the first interface to initiate CNTs-cell interactions. In the present study, the inhibiting effect of multiwalled carbon nanotubes on the extrusion of fluorescein in human glioma cells was demonstrated using two procedures. To provide clues to explanation of this effect, intracellular glutathione content and reactive oxygen species production were determined as fluorescein is a specific substrate of cell membrane multidrug resistance-related protein whose transport activity requires glutathione which can be depleted under oxidative stress. The plasma membrane potential was also probed as the susceptibility of fluorescein efflux to modulation of the plasma membrane potential has been documented. Results showed a remarkable decrease in cellular glutathione level as well as an increase in reactive oxygen species production. Probe staining also indicated decreased plasma membrane potential. The data suggested that multiwalled carbon nanotubes may affect the transport activity of cell membrane multidrug resistance-related protein through reduction of intracellular glutathione content. Hypopolarization of the plasma membrane may also contribute to MWCNTs' effect. Implications of these findings are discussed.