Identification of a Novel Peptide Ligand of Human Transfrrin Receptor 1 for Targeted Tumor Delivery Drug

Human transferrin receptor 1 (TfR1) is expressed on malignant cells at levels several fold higher than those on normal cells and its expression can be correlated with tumor stage or cancer progression. It is a potentially rational target for drug delivery. To identify novel ligands which can recognize the TfR1 specifically, a random phage displayed 12-mer peptide library was screened and two consensus motifs of the peptides which are displayed by the positive phages RXR and RXXXR (x is any amino acid) were yield. The phage displaying peptide SPRPRHTLRLSL (designated as B18) exhibited the highest affinity to TfR1 in phage ELISA and B18 could bind to TfR1 specifically in a dose dependent manner. The flow cytometry assay and immunocellularchemistry assay showed that the B18 could bind to TfR1 positive carcinoma cells with specificity. In addition, the biodistribution assay indicated that B18 could home to TfR1 positive tumor tissue specifically. Our study suggests that the peptide exhibited by B18 is a potentially promising targeting peptide for tumor diagnosis and treatment. Keywords: TfR1, phage display, peptide, malignant cells, normal cells, tumor, cancer progression, flow cytometry assay