Selection of Promiscuous Anti-Cancer Phage Proteins for Tumor Targeted Nanomedicines

Abstract

Cancer remains one of the leading causes of death and requires novel approaches in both management and treatment. Tumor targeting ligands have been identified to a variety of human cancer cell lines using phage display selection techniques and used to modify current standard of care drugs and drug delivery systems with some success. However, there are still serious limitations in their use. One limitation of using targeted chemotherapy is the heterogeneity of tumor cells, both within the same tumor and across distant lesions. This heterogeneity can complicate identification of specific targeting ligands that will be effective for treating not only the primary tumor, but distant metastatic lesions. Work described below addresses the issue of tumor cell heterogeneity by using a novel, multi-target biopanning (screening) scheme involving landscape phage display libraries to select promiscuous cancer cell binding ligands. The pan-cancer binding ligands were shown to be similar to those selected previously against a variety of cancer types in addition to the cancer cell lines screened in this study. Phage displaying the fusion peptides GSLEEVSTL and GEFDELMTM were used to modify liposomal doxorubicin and the modified liposomes showed an increase of cytotoxicity of up to 8.1-fold in several lung and pancreatic cancer cell lines. Results indicate that a multi-target cell phage screening can be used effectively in heterogeneous tumor cell populations for identification of promiscuous cancer cell binding ligands.