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Peptide-Functionalized Luminescent Iridium Complexes for Lifetime Imaging of CXCR4 Expression

Authors

  • Dr. Joeri Kuil,

    1. Division of Diagnostic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam (The Netherlands)
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    • These authors contributed equally to this work.

  • Dr. Peter Steunenberg,

    1. Supramolecular Chemistry and Technology, MIRA Institute for Biomedical Chemistry and Technical Medicine, MESA+ Institute for Nanotechnology, University of Twente, P. O. Box 217, 7500 AE Enschede (The Netherlands)
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    • These authors contributed equally to this work.

  • Dr. Patrick T. K. Chin,

    1. Netherlands Organization for Applied Scientific Research (TNO), Utrechtseweg 48, 3704 HE Zeist (The Netherlands)
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  • Joppe Oldenburg,

    1. Division of Diagnostic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam (The Netherlands)
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  • Dr. Kees Jalink,

    1. Division of Cell Biology I, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam (The Netherlands)
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  • Dr. Aldrik H. Velders,

    Corresponding author
    1. Supramolecular Chemistry and Technology, MIRA Institute for Biomedical Chemistry and Technical Medicine, MESA+ Institute for Nanotechnology, University of Twente, P. O. Box 217, 7500 AE Enschede (The Netherlands)
    • Supramolecular Chemistry and Technology, MIRA Institute for Biomedical Chemistry and Technical Medicine, MESA+ Institute for Nanotechnology, University of Twente, P. O. Box 217, 7500 AE Enschede (The Netherlands)
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  • Dr. Fijs W. B. van Leeuwen

    Corresponding author
    1. Division of Diagnostic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam (The Netherlands)
    • Division of Diagnostic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam (The Netherlands)
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Abstract

The chemokine receptor 4 (CXCR4) is over-expressed in 23 types of cancer in which it plays a role in, among others, the metastatic spread. For this reason it is a potential biomarker for the field of diagnostic oncology. The antagonistic Ac-TZ14011 peptide, which binds to CXCR4, has been conjugated to luminescent iridium dyes to allow for CXCR4 visualization. The iridium dyes are cyclometalated octahedral iridium(III) 2-phenylpyridine complexes that can be functionalized with one, two or three targeting Ac-TZ14011 peptides. Confocal microscopy and fluorescence lifetime imaging microscopy (FLIM) showed that the peptide–iridium complex conjugates can be used to visualize CXCR4 expression in tumor cells. The CXCR4 receptor affinity and specific cell binding of the mono-, di- and trimeric peptide derivatives were assessed by using flow cytometry. The three derivatives possessed nanomolar receptor affinity and could distinguish between cell lines with different CXCR4 expression levels. This yields the first example of a neutral iridium(III) complex functionalized with peptides for FLIM-based visualization of a cancer associated membrane receptor.

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