JBIC Journal of Biological Inorganic Chemistry

, Volume 22, Issue 8, pp 1295–1304 | Cite as

A fluorescent oxaliplatin derivative for investigation of oxaliplatin resistance using imaging techniques

  • Ganna V. Kalayda
  • Maximilian Kullmann
  • Markus Galanski
  • Sabrina Gollos
Original Paper

Abstract

Oxaliplatin is the backbone of chemotherapy for advanced colorectal cancer and undergoes clinical trials for treatment of other tumour entities. However, acquired resistance is a major hurdle. Confocal microscopy is a useful tool to get an insight into the mechanisms of resistance but it requires fluorescent compounds. This work describes the synthesis of the novel oxaliplatin derivative (CFDA-oxPt) featuring 5(6)-carboxyfluorescein diacetate and evaluation of its applicability for the investigation of oxaliplatin resistance using imaging techniques. CFDA-oxPt was somewhat less cytotoxic than oxaliplatin in sensitive colorectal cancer cells, with EC50 values of 26 and 5.8 µM, respectively. Nevertheless, the potency of the novel complex was significantly decreased to the EC50 of 711.2 µM in oxaliplatin-resistant cells, as was the case for oxaliplatin (EC50 = 81 µM). After incubation, both nuclear and cytosolic localisation was observed. Over time CFDA-oxPt concentrated near the cell membrane and in the vesicular structures, in contrast to the platinum-free label, which was rapidly excreted. These findings suggest that CFDA-oxPt can be used to study oxaliplatin resistance and open the route to new fluorophore-tethered oxaliplatin derivatives.

Keywords

Platinum complexes Fluorescent probes Live-cell microscopy Cellular distribution 

Notes

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (JA 817/4-1). The authors are grateful to Prof. Dr. Ulrich Jaehde for helpful discussions and to Prof. Dr. Christa E. Müller for providing laboratory facilities.

Supplementary material

775_2017_1502_MOESM1_ESM.pdf (717 kb)
Supplementary material 1 (PDF 716 kb)

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Copyright information

© SBIC 2017

Authors and Affiliations

  • Ganna V. Kalayda
    • 1
  • Maximilian Kullmann
    • 1
  • Markus Galanski
    • 2
  • Sabrina Gollos
    • 3
  1. 1.Department of Clinical Pharmacy, Pharma Centre Bonn, Institute of PharmacyUniversity of BonnBonnGermany
  2. 2.Institute of Inorganic ChemistryUniversity of ViennaViennaAustria
  3. 3.Department of Pharmaceutical Chemistry, Pharma Centre Bonn, Institute of PharmacyUniversity of BonnBonnGermany

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