1. Academic Validation
  2. Single-Cell and Bulk ICP-MS Investigation of Accumulation Patterns of Pt-based Metallodrugs in Cisplatin-Sensitive and -Resistant Cell Models

Single-Cell and Bulk ICP-MS Investigation of Accumulation Patterns of Pt-based Metallodrugs in Cisplatin-Sensitive and -Resistant Cell Models

  • Metallomics. 2022 Oct 22;mfac085. doi: 10.1093/mtomcs/mfac085.
Si Ying Lim 1 2 Zhi En Low 2 Regina Pei Woon Tan 2 Zhi Chiaw Lim 2 Wee Han Ang 1 2 Tetsuo Kubota 3 Michiko Yamanaka 3 Steven Pang 4 Erhan Simsek 4 Sam Fong Yau Li 1 2
Affiliations

Affiliations

  • 1 NUS Graduate School's Integrative Sciences & Engineering Programme (ISEP), National University of Singapore, University Hall, Tan Chin Tuan Wing, Singapore 119077, Singapore.
  • 2 Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
  • 3 Agilent Technologies Japan Ltd, 9-1 Takakura-machi, Hachioji-shi, Tokyo 192-8510, Japan.
  • 4 Agilent Technologies Singapore Pte Ltd, 1 Yishun Avenue 7, Singapore 768923, Singapore.
Abstract

In research enabling preclinical development and attaining a deeper understanding of the behaviour 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 pre-existing 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.

Keywords

A2780; Carboplatin; Cisplatin; Oxaliplatin; Pt chemotherapeutic drug; Single-cell ICP-MS.

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