EDB Fibronectin Specific Peptide for Prostate Cancer Targeting

Abstract

Extradomain-B fibronectin (EDB-FN), one of the oncofetal fibronectin (onfFN) isoforms, is a high-molecular-weight glycoprotein that mediates cell adhesion and migration. The expression of EDB-FN is associated with a number of cancer-related biological processes such as tumorigenesis, angiogenesis, and epithelial-to-mesenchymal transition (EMT). Here, we report the development of a small peptide specific to EDB-FN for targeting prostate cancer. A cyclic nonapeptide, CTVRTSADC (ZD2), was identified using peptide phage display. A ZD2-Cy5 conjugate was synthesized to accomplish molecular imaging of prostate cancer in vitro and in vivo. ZD2-Cy5 demonstrated effective binding to up-regulated EDB-FN secreted by TGF-β-induced PC3 cancer cells following EMT. Following intravenous injections, the targeted fluorescent probe specifically bound to and delineated PC3-GFP prostate tumors in nude mice bearing the tumor xenografts. ZD2-Cy5 also showed stronger binding to human prostate tumor specimens with a higher Gleason score (GS9) compared to those with a lower score (GS 7), with no binding in benign prostatic hyperplasia (BPH). Thus, the ZD2 peptide is a promising strategy for molecular imaging and targeted therapy of prostate cancer.

Targeting fibronectin for cancer imaging and therapy

“…A small cyclic nonapeptide ZD2 of the sequence of CTVRTSADC was recently identified using peptide phage display to target EDB. This peptide demonstrated excellent specific targeting to tumor in vivo 101 . Another class of FN-targeting ligands is the peptides that target fibronectin-fibrin complexes.…”

“…Even though limited studies have been done with a specific focus on FN-targeting optical imaging probe for in vivo cancer imaging 101, 125 , FN-targeting fluorescent probes have been developed in most studies for validating tumor targeting efficiency of the ligands. The probes also have been tested for in vivo diagnosis of other diseases, including rheumatoid arthritis, atherosclerosis, etc.…”

A New Magnetic Resonance Imaging Probe Specifically Targeting Vascular Endothelial Growth Factor Receptor 2:Synthesis, Characterization and Biological Evaluation

“…It is found that efficient accumulation of the targeted contrast agent was observed in the tumour area at 5 min, however the contrast continuously decreased faster after 5 min for SGd than VGd. Previously, the other peptides used for MRI targeting imaging, including CREKA, ZD2 and CLT1, also indicated similar findings that agents modified with targeting peptides would provide enhanced contrast and also slower contrast decrease with scanning time 2,11,21 . As illustrated in Scheme 1, the VGd, once injected via tail vein, circulated in the blood vessel and conveniently bound to the VEGFR2 highly expressed in tumours, resulting in the improved tumour uptake of VGd compared with SGd.…”

Magnetic resonance molecular imaging for non-invasive precision cancer diagnosis

“…Extradomain B-fibronectin (EDB-FN) is a cancer-related fibronectin isoform highly expressed in the ECM of various aggressive human cancers, but not in normal tissues [19, 20]. It is a marker of epithelial-to-mesenchymal transition (EMT) and plays a key role in EMT induction, cancer cell stemness, cancer proliferation, and angiogenesis.…”