Abstract:
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 non-toxic (IC50 > 100 µM) to HT-29 cells, both in the
dark and upon light activation (1 J/cm
). 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.
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