Inhibitor-Decorated Polymer Conjugates Targeting Fibroblast Activation Protein.
Petra DvořákováPetr BušekTomáš KnedlíkJiří SchimerTomas EtrychLibor KostkaLucie Stollinová ŠromováVladimír ŠubrPavel ŠáchaAleksi ŠedoJan KonvalinkaPublished in: Journal of medicinal chemistry (2017)
Proteases are directly involved in cancer pathogenesis. Expression of fibroblast activation protein (FAP) is upregulated in stromal fibroblasts in more than 90% of epithelial cancers and is associated with tumor progression. FAP expression is minimal or absent in most normal adult tissues, suggesting its promise as a target for the diagnosis or treatment of various cancers. Here, we report preparation of a polymer conjugate (an iBody) containing a FAP-specific inhibitor as the targeting ligand. The iBody inhibits both human and mouse FAP with low nanomolar inhibition constants but does not inhibit close FAP homologues dipeptidyl peptidase IV, dipeptidyl peptidase 9, and prolyl oligopeptidase. We demonstrate the applicability of this iBody for the isolation of FAP from cell lysates and blood serum as well as for its detection by ELISA, Western blot, flow cytometry, and confocal microscopy. Our results show the iBody is a useful tool for FAP targeting in vitro and potentially also for specific anticancer drug delivery.
Keyphrases
- cancer therapy
- poor prognosis
- drug delivery
- flow cytometry
- binding protein
- gene expression
- single cell
- long non coding rna
- childhood cancer
- squamous cell carcinoma
- cell therapy
- papillary thyroid
- mass spectrometry
- extracellular matrix
- protein protein
- gold nanoparticles
- deep learning
- drug release
- south africa
- big data
- simultaneous determination
- sensitive detection
- replacement therapy