Single cell ICP-MS for the assessment of potential nephroprotectors against cisplatin

Abstract

The use of cisplatin chemotherapy is often limited by the occurrence of various side effects, with renal toxicity being one of the most serious. In the present work, a single cell ICP-MS (scICP-MS) methodology was optimised to evaluate the cellular uptake of cisplatin in the presence of three potential nephroprotectors such as chitosan-stabilised selenium nanoparticles (Ch-SeNPs), selenomethionine (SeMet) and methionine (Met). Human telomerase reverse transcriptase-immortalised renal proximal tubular epithelial cells (RPTEC/TERT1) and human cervical cancer cells (HeLa) were employed with this aim. In both cell lines, a decrease in the intracellular Pt levels when using SeMet and Met as coadjuvants was revealed, involving less toxicity in renal cells but no reduction in the anticancer effect after measurement of cell viability by MTT assays. In contrast, Ch-SeNPs had no effect on the internalisation of the Pt-drug but enhanced its antitumour efficacy with no additional damage to kidney cells. This would allow decreasing cisplatin doses which would in turn reduce nephrotoxicity risk. Se determination by scICP-MS was also done to study the cell uptake of the selenocompounds, in addition to transmission electron microscopy (TEM) analysis of Ch-SeNPs internalisation. The effects of both SeMet and Ch-SeNPs were confirmed despite the Pt-drug was shown to induce a decrease in cell uptake. Results were compared by two different scICP-MS settings (a conventional introduction system and a special configuration for intact cells), as well as with the classical digestion-based bulk analysis. Our results demonstrate the potential of scICP-MS for metallomic cellular studies to improve cisplatin-based therapies.