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Article

Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures

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Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
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Department for BioMedical Research DBMR, University of Bern, 3008 Bern, Switzerland
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Institute of Nanotechnology and Advanced Materials & Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel
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Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP), University of Bern, 3012 Bern, Switzerland
*
Authors to whom correspondence should be addressed.
Academic Editor: Giovanni Natile
Int. J. Mol. Sci. 2021, 22(17), 9468; https://doi.org/10.3390/ijms22179468
Received: 2 August 2021 / Revised: 27 August 2021 / Accepted: 30 August 2021 / Published: 31 August 2021
(This article belongs to the Special Issue The Discovery and Development of Cisplatin)
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. View Full-Text
Keywords: NSCLC; cisplatin; chemotherapy; single cell ICP-MS; cisplatin resistance; nuclear uptake NSCLC; cisplatin; chemotherapy; single cell ICP-MS; cisplatin resistance; nuclear uptake
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MDPI and ACS Style

Galé, A.; Hofmann, L.; Lüdi, N.; Hungerbühler, M.N.; Kempf, C.; Heverhagen, J.T.; von Tengg-Kobligk, H.; Broekmann, P.; Ruprecht, N. Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures. Int. J. Mol. Sci. 2021, 22, 9468. https://doi.org/10.3390/ijms22179468

AMA Style

Galé A, Hofmann L, Lüdi N, Hungerbühler MN, Kempf C, Heverhagen JT, von Tengg-Kobligk H, Broekmann P, Ruprecht N. Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures. International Journal of Molecular Sciences. 2021; 22(17):9468. https://doi.org/10.3390/ijms22179468

Chicago/Turabian Style

Galé, Audrey, Lukas Hofmann, Nicola Lüdi, Martin N. Hungerbühler, Christoph Kempf, Johannes T. Heverhagen, Hendrik von Tengg-Kobligk, Peter Broekmann, and Nico Ruprecht. 2021. "Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures" International Journal of Molecular Sciences 22, no. 17: 9468. https://doi.org/10.3390/ijms22179468

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