Single-cell and bulk ICP–MS investigation of accumulation patterns of Pt-based metallodrugs in cisplatin-sensitive and -resistant cell models

Abstract

In research enabling preclinical development and attaining a deeper understanding of the behavior of metallodrugs in cancer cells with acquired resistance, intracellular Pt accumulation could be considered an important biomarker and analytical focus. In this work, Pt accumulation patterns in terms of the number of cells and Pt mass in single cells were precisely defined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in a fast time-resolved analysis mode. This technique is otherwise known as single-cell (SC)-ICP-MS. By applying the nascent and validated SC-ICP-MS technique, comparisons across three Pt drugs (cisplatin, carboplatin, and oxaliplatin) in the A2780 and A2780cis ovarian cancer cell models could be made. Additional roles of transporters on top of passive diffusion and the drugs' bioactivity could be postulated. The SC-ICP-MS-based observations also served as a cross-validation point to augment preexisting research findings on Pt-resistance mechanisms. Conjectures regarding S and Fe metabolism were also derived based on an additional and direct ICP-MS analysis of endogenous elements. Overall, our work not only confirms the utility of SC-ICP-MS in chemotherapeutic research, but also provided insights into further ICP-MS-based analytical capacities to be developed.