NanoSIMS combined with fluorescence microscopy as a tool for subcellular imaging of isotopically labeled platinum-based anticancer drugs
- Author(s)
- Anton A. Legin, Arno Schintlmeister, Michael A. Jakupec, Mathea Sophia Galanski, Irene Lichtscheidl-Schultz, Michael Wagner, Bernhard K. Keppler
- Abstract
Multi-elemental, isotope selective nano-scale secondary ion mass spectrometry (NanoSIMS) combined with confocal laser-scanning microscopy was used to characterize the subcellular distribution of
15N-labeled cisplatin in human colon cancer cells. These analyses indicated predominant cisplatin colocalisation with sulfur-rich structures in both the nucleus and cytoplasm. Furthermore, colocalisation of platinum with phosphorus-rich chromatin regions was observed, which is consistent with its binding affinity to DNA as the generally accepted crucial target of the drug. Application of
15N-labeled cisplatin and subsequent measurement of the nitrogen isotopic composition and determination of the relative intensities of platinum and nitrogen associated secondary ion signals in different cellular compartments with NanoSIMS suggested partial dissociation of Pt-N bonds during the accumulation process, in particular within nucleoli at elevated cisplatin concentrations. This finding raises the question as to whether the observed intracellular dissociation of the drug has implications for the mechanism of action of cisplatin. Within the cytoplasm, platinum mainly accumulated in acidic organelles, as demonstrated by a direct combination of specific fluorescent staining, confocal laser scanning microscopy and NanoSIMS. Different processing of platinum drugs in acidic organelles might be relevant for their detoxification, as well as for their mode of action.
- Organisation(s)
- Department of Inorganic Chemistry
- Journal
- Chemical Science
- Volume
- 5
- Pages
- 3135-3143
- No. of pages
- 9
- ISSN
- 2041-6520
- DOI
- https://doi.org/10.1039/c3sc53426j
- Publication date
- 2014
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301904 Cancer research, 210001 Nanoanalytics
- Keywords
- ASJC Scopus subject areas
- General Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/95a99184-b1ce-4168-bb85-261f9e968652