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

Galé, Audrey; Hofmann, Lukas; Lüdi, Nicola; Hungerbühler, Martin Nils; Kempf, Christoph; Heverhagen, Johannes Thomas; von Tengg-Kobligk, Hendrik; Broekmann, Peter; Ruprecht, Nico (2021). Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures. International journal of molecular sciences, 22(17) MDPI 10.3390/ijms22179468

[img]
Preview
Text
Nico_Beyond.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie

UniBE Contributor:

Lüdi, Nicola Christian; Hungerbuehler, Martin; Kempf, Christoph; Heverhagen, Johannes; von Tengg-Kobligk, Hendrik; Broekmann, Peter and Ruprecht, Nico

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1422-0067

Publisher:

MDPI

Language:

English

Submitter:

Maria de Fatima Henriques Bernardo

Date Deposited:

30 Sep 2021 12:12

Last Modified:

30 Sep 2021 12:12

Publisher DOI:

10.3390/ijms22179468

PubMed ID:

34502377

Uncontrolled Keywords:

NSCLC chemotherapy cisplatin cisplatin resistance nuclear uptake single cell ICP-MS

BORIS DOI:

10.48350/159303

URI:

https://boris.unibe.ch/id/eprint/159303

Actions (login required)

Edit item Edit item
Provide Feedback