Novel challenges in exploring peptide ligands and corresponding tissue-specific endothelial receptors

The structural and molecular diversity of vascular endothelium may depend on the functional state and tissue localisation of its cells. Tumour vasculature expresses a number of molecular markers that distinguish it from normal vasculature. In cancer, the determinant of specific tumour vasculature heterogeneity is, in part, dictated by dysregulated expression of tumour-derived angiogenic factors. The identification of molecular 'addresses' on the surface of tumour vasculature has significantly contributed to the selection of targets, which have been used for delivering therapeutic and imaging agents in cancer. Cytotoxic drug, pro-apoptotic peptides, protease inhibitors, and gene therapy vectors have been successfully linked to peptides and delivered to tumour sites with an improved experimental therapy. Different diagnostic and therapeutic compounds can be efficiently targeted to specific receptors on vascular endothelial cells; the development of ligand-directed vector tools may promote systemic targeted gene delivery. Here, we review the very recent advances in the identification of peptide ligands and their corresponding tissue-specific endothelial receptors through the phage display technology with emphasis on ligand-directed delivery of therapeutic agents and targeted gene therapy.