Peptide-functionalized luminescent iridium complexes for lifetime imaging of CXCR4 expression

Chembiochem. 2011 Aug 16;12(12):1897-903. doi: 10.1002/cbic.201100271. Epub 2011 Jul 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology
  • Female
  • Flow Cytometry
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / metabolism
  • Fluorescent Dyes / pharmacology
  • Gene Expression
  • Humans
  • Iridium / chemistry*
  • Iridium / metabolism
  • Kinetics
  • Ligands
  • Luminescence
  • Microscopy, Fluorescence
  • Molecular Imaging / methods*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Protein Binding
  • Pyridines / chemistry
  • Receptors, CXCR4 / chemistry
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*


  • Coordination Complexes
  • Fluorescent Dyes
  • Ligands
  • Peptides
  • Pyridines
  • Receptors, CXCR4
  • 2-phenylpyridine
  • Iridium