Application of Bld-1-Embedded Elastin-Like Polypeptides in Tumor Targeting

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. B₅V₆₀ containing five Bld-1 peptides and non-targeted ELP₇₇ with a thermal phase-transition over 37 °C were analyzed to determine their bioactivities. Further studies confirmed the superior binding ability of B₅V₆₀ to bladder tumor cells and the cellular accumulation of B₅V₆₀ in cancer cells was dependent on the expression level of sialyl-Tn antigen (STn), a tumor-associated carbohydrate antigen. Additionally, B₅V₆₀ 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 B₅V₆₀ showed high potential as a novel carrier for STn-specific targeted cancer therapy or other therapeutic applications.