Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics.
Epidermal growth factor receptor (ErbB1, EGFR) is overexpressed in a variety of human cancer cells. It has been considered as a rational target for drug delivery. To identify novel ligands with specific binding capabilities to EGFR, we screened a phage display peptide library and found an enriched phage clone encoding the amino acid sequence YHWYGYTPQNVI (designated as GE11). Competitive binding assay and Scatchard analysis revealed that GE11 peptide bound specifically and efficiently to EGFR with a dissociation constant of approximately 22 nM, but with much lower mitogenic activity than with EGF. We showed that the peptides were internalized preferentially into EGFR highly expressing cells, and they accumulated in EGFR overexpressing tumor xenografts after i.v. delivery in vivo. In gene delivery studies, GE11-conjugated polyethylenimine (PEI) vectors were less mitogenic, but still quite efficient at transfecting genes into EGFR highly expressing cells and tumor xenografts. Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR.
Li
Zonghai
Z
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Medical College of Shanghai Jiao Tong University, Shanghai, China.
Zhao
Ruijiao
R
Wu
Xianghua
X
Sun
Ye
Y
Yao
Ming
M
Li
Jinjun
J
Xu
Yuhong
Y
Gu
Jianren
J
D045744:Cell Line, Tumor; D003851:Deoxyribonucleases / Q000378:metabolism; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000737:chemistry; D066246:ErbB Receptors / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007262:Infusions, Intravenous; D007454:Iodides / Q000737:chemistry; D020014:K562 Cells; D007700:Kinetics; D008024:Ligands; D009368:Neoplasm Transplantation; D018739:Oncogene Proteins v-erbB / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011485:Protein Binding; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014162:Transfection
D007454:Iodides; D008024:Ligands; D018739:Oncogene Proteins v-erbB; D019151:Peptide Library; D010455:Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; D004815:Epidermal Growth Factor; D011094:Polyethyleneimine; D066246:ErbB Receptors; D003851:Deoxyribonucleases; C022616:thiazolyl blue