Karim Aljakouch1,2, Tatjana Lechtonen1,2, Hesham K. Yosef1,2, Mohamad K. Hammoud1, Wissam Alsaidi1, Carsten Kötting1, Carolin Mügge3, Robert Kourist4, Samir F. El‐Mashtoly1, Klaus Gerwert1
1Biophysics Department, Ruhr-University Bochum, Germany
2these authors contributed equally to this work
3Junior Research Group for Microbial Biotechnology, Ruhr-University Bochum, Germany
4Institute of Molecular Biotechnology, Graz University of Technology, Austria
Tóm tắt
AbstractTyrosine kinase receptors are one of the main targets in cancer therapy. They play an essential role in the modulation of growth factor signaling and thereby inducing cell proliferation and growth. Tyrosine kinase inhibitors such as neratinib bind to EGFR and HER2 receptors and exhibit antitumor activity. However, little is known about their detailed cellular uptake and metabolism. Here, we report for the first time the intracellular spatial distribution and metabolism of neratinib in different cancer cells using label‐free Raman imaging. Two new neratinib metabolites were detected and fluorescence imaging of the same cells indicate that neratinib accumulates in lysosomes. The results also suggest that both EGFR and HER2 follow the classical endosome lysosomal pathway for degradation. A combination of Raman microscopy, DFT calculations, and LC‐MS was used to identify the chemical structure of neratinib metabolites. These results show the potential of Raman microscopy to study drug pharmacokinetics.
