Figure 1: Selection of peptides that target tumor blood vessels using in vivo phage display. Peptide or antibody libraries are expressed as fusion proteins with a coat protein (pIII) of a bacteriophage, and the fused proteins are displayed on the surface of the virion. A phage-displayed peptide library was injected through the tail vein of tumor-bearing mice. Eight minutes after injection, the mice were perfused through the heart. Phage recovered from the tumor was amplified and reinjected in mice for another four rounds. Tumor-targeting phages were further identified by in vivo tumor-homing assay, synthetic peptide binding and competition assay, and immunohistochemical staining. The identified peptides can be used as ligands to recognize cell surface markers or tumor antigens to develop targeted therapy. SCID mice bearing human cancer xenografts were successfully treated with ligand-conjugated antiangiogenic targeting liposomes.