Abstract
Expression of various molecules on the surface of cancer cells compared to normal cells creates a platform for the generation of various drug vehicles for targeted therapy. Multiple interactions between ligands and their receptors mediated by targeting peptide-modified polymer could enable simultaneous delivery of a drug selectively to target tumor cells, thus limiting side effects resulting from non-specific drug delivery. In this study, we synthesized a novel tumor targeting system by using two key elements: (1) Bld-1 peptide (SNRDARRC), a recently reported bladder tumor targeting peptide identified by using a phage-displayed peptide library, and (2) ELP, a thermally responsive polypeptide. B(5)V(60) containing five Bld-1 peptides and non-targeted ELP(77) with a thermal phase-transition over 37 °C were analyzed to determine their bioactivities. Further studies confirmed the superior binding ability of B(5)V(60) to bladder tumor cells and the cellular accumulation of B(5)V(60) in cancer cells was dependent on the expression level of sialyl-Tn antigen (STn), a tumor-associated carbohydrate antigen. Additionally, B(5)V(60) displayed excellent localization in bladder tumor xenograft mice after intravenous injection and was strictly confined to sialyl-Tn antigen-overexpressing tumor tissue. Thus, our newly designed B(5)V(60) showed high potential as a novel carrier for STn-specific targeted cancer therapy or other therapeutic applications.