title: Phthalocyanine-peptide conjugates for epidermal growth factor receptor targeting.
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 nontoxic (IC(50) > 100 μM) to HT-29 cells, both in the dark and upon light activation (1 J/cm(2)). 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.
authors.affiliation: Louisiana State University, Department of Chemistry, Baton Rouge, Louisiana 70803, USA.
authors.forename: Benson G
authors.initials: BG
authors.lastname: Ongarora
authors.forename: Krystal R
authors.initials: KR
authors.lastname: Fontenot
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Hu
authors.forename: Inder
authors.initials: I
authors.lastname: Sehgal
authors.forename: Seetharama D
authors.initials: SD
authors.lastname: Satyanarayana-Jois
authors.forename: M Graça H
authors.initials: MG
authors.lastname: Vicente
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D015179:Colorectal Neoplasms / Q000175:diagnosis; D066246:ErbB Receptors / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000378:metabolism; D054833:Isoindoles; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D014709:Vero Cells
chemical_list: D005456:Fluorescent Dyes; D007211:Indoles; D054833:Isoindoles; D008024:Ligands; D009842:Oligopeptides; D010455:Peptides; C540794:leucyl-alanyl-arginyl-leucyl-leucyl-threonine; D066246:ErbB Receptors; C013647:phthalocyanine