Chemo-Radiative Stress of Plasma as a Modulator of Charge-Dependent Nanodiamond Cytotoxicity

Efficient and selective internalization of nanoscale diamonds (also termed nanodiamonds, NDs) by living cells is of fundamental importance for their bionanotechnological applications. The biocompatibility of NDs is well established and has been suggested to arise from the limited membrane perturbation during their cellular translocation. However, the latter may be affected when cells are subjected to external stress. This study shows that the oxidative stress generated by atmospheric pressure cold plasmas (APCP) alters cell sensitivity to NDs, and their cytotoxicity profile. Both positively and negatively charged NDs are nontoxic to cells, here Saccharomyces cerevisiae and human cell lines, i.e., near-normal human mammary epithelial cells (MCF-10A) and breast cancer cells (MDA-MB-468 and T47D), unless the APCP stress is introduced. A brief exposure of the cells to APCP leads to a significant increase in their ND affinity (uptake and/or surface attachment) and intracellular ROS accumulation, particularly for positively charged NDs and both yeast and cancer cells. A concomitant decrease in cell viability and yeast cell growth, reflected by longer lag phases and lower cell density after 24 h of incubation, demonstrates a considerably enhanced ND toxicity to these cells. These results suggest that chemo-radiative stress, such as that produced by plasma, may influence the toxicity of nanoparticles to different cells, with specificity achieved through controlling particle charges. Moreover, since oxidative stress is not only associated with the use of APCP but can arise unintentionally within an organism and/or in the environment, these findings may have broader implications for the use of nontoxic nanoparticles in bionanotechnology in general.