Phthalocyanine-peptide conjugates for epidermal growth factor receptor targeting
Four phthalocyanine (Pc)-peptide conjugates designed to target the epidermal growth factor receptor (EGFR) were synthesized and evaluated in vitro using four cell lines: human carcinoma A431 and HEp2, human colorectal HT-29, and kidney Vero (negative control) cells. Two peptide ligands for EGFR were investigated: EGFR-L1 and -L2, bearing 6 and 13 amino acid residues, respectively. The peptides and Pc-conjugates were shown to bind to EGFR using both theoretical (Autodock) and experimental (SPR) investigations. The Pc-EGFR-L1 conjugates 5a and 5b efficiently targeted EGFR and were internalized, in part due to their cationic charge, whereas the uncharged Pc-EGFR-L2 conjugates 4b and 6a poorly targeted EGFR maybe due to their low aqueous solubility. All conjugates were nontoxic (IC50 > 100 μM) to HT-29 cells, both in the dark and upon light activation (1 J/cm2). Intravenous (iv) administration of conjugate 5b into nude mice bearing A431 and HT-29 human tumor xenografts resulted in a near-IR fluorescence signal at ca. 700 nm, 24 h after administration. Our studies show that Pc-EGFR-L1 conjugates are promising near-IR fluorescent contrast agents for CRC and potentially other EGFR overexpressing cancers. © 2012 American Chemical Society.
Publication Source (Journal or Book title)
Journal of Medicinal Chemistry
Ongarora, B., Fontenot, K., Hu, X., Sehgal, I., Satyanarayana-Jois, S., & Vicente, D. (2012). Phthalocyanine-peptide conjugates for epidermal growth factor receptor targeting. Journal of Medicinal Chemistry, 55 (8), 3725-3738. https://doi.org/10.1021/jm201544y