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Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures
Audrey Galé1,2, Lukas Hofmann3, Nicola Lüdi4
1Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Abstract:
Platinum compounds such as cisplatin (cisPt) embody the backbone of combination chemotherapy protocols against advanced lung cancer. However, their efficacy is primarily limited by inherent or acquired platinum resistance, the origin of which has not been fully elucidated yet, although of paramount interest. Using single cell inductively coupled plasma mass spectrometry (SC-ICP-MS), this study quantifies cisPt in single cancer cells and for the first time in isolated nuclei. A comparison of cisPt uptake was performed between a wild type (wt) cancer cell line and related resistant sublines. In both, resistant cells, wt cells, and their nuclei, cisPt uptake was measured at different incubation times. A lower amount of cisPt was found in resistant cell lines and their nuclei compared to wt cells. Moreover, the abundance of internalized cisPt decreased with increasing resistance. Interestingly, concentrations of cisPt found within the nuclei were higher than compared to cellular concentrations. Here, we show, that SC-ICP-MS allows precise and accurate quantification of metallodrugs in both single cells and cell organelles such as nuclei. These findings pave the way for future applications investigating the potency and efficacy of novel metallodrugs developed for cancer treatment.
Insights
Platinum-based chemotherapy, like cisplatin (cisPt), faces resistance in lung cancer. This study used SC-ICP-MS to show resistant cells internalize less cisPt, with higher concentrations found in nuclei, aiding new drug development.
Area of Science:
- Oncology
- Analytical Chemistry
- Cell Biology
Background:
- Platinum compounds, such as cisplatin (cisPt), are crucial in advanced lung cancer chemotherapy.
- Platinum resistance significantly limits the efficacy of these vital cancer treatments.
- The precise mechanisms underlying platinum resistance remain incompletely understood.
Purpose of the Study:
- To quantify cisplatin (cisPt) in single cancer cells and isolated nuclei using SC-ICP-MS.
- To compare cisPt uptake between wild-type (wt) and platinum-resistant cancer cell lines.
- To investigate the distribution of cisPt within cellular compartments in relation to resistance levels.
Main Methods:
- Single cell inductively coupled plasma mass spectrometry (SC-ICP-MS) for precise metallodrug quantification.
- Culturing of wild-type (wt) and platinum-resistant cancer cell lines.
- Measurement of intracellular and intranuclear cisPt concentrations at various incubation times.
Main Results:
- Resistant cell lines and their nuclei exhibited lower cisPt uptake compared to wt cells.
- Internalized cisPt levels decreased proportionally with increasing platinum resistance.
- Nuclear cisPt concentrations were found to be higher than overall cellular concentrations.
Conclusions:
- SC-ICP-MS enables accurate quantification of metallodrugs in single cells and organelles like nuclei.
- Reduced cisPt uptake in resistant cells contributes to treatment limitations.
- This methodology supports the development and evaluation of novel metallodrugs for cancer therapy.
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