ToF-SIMS Imaging of Intracellular ³⁹K/⁴⁰Ca Changes induced by ZnO-containing Nanomaterials

We prepared ZnO-containing nanomaterials of different-sized native ZnO and isotope-enriched 68ZnO nanoparticles (NPs) with well-characterized composition and applied them to HaCaT cells for in vitro cytotoxicity study. ToF-SIMS was applied to probe spatially-resolved intracellular changes. Elevated level of intracellular Zn correlated well with decreased 39K/40Ca upon increased ZnO NPs exposure, indicating that the dissolving behavior of ZnO NPs played an important role in inducing cytotoxicity. Furthermore, the coherency of spatial distribution between elevated Zn and decreased 39K/40Ca leads us to propose the presence of local cytotoxicity effect by ZnO NPs. Similar results were obtained irrespective of the use of native or isotope-enriched ZnO NPs, indicating the negligible contribution to cytotoxicity from intrinsic Zn2+.