HUNTER-KILLER PEPTIDES AND METHODS OF USE

摘要

The present invention provides homing conjugates containing an antimicrobial peptide and a tumor homing molecule, wherein the tumor homing molecule comprises a dimer of two endothelium-homing peptide monomers, wherein the conjugate homes to and is internalized by a tumor cell type or tissue comprising angiogenic endothelial cells and exhibits high toxicity thereto, wherein the high toxicity is due to disruption of mitochondrial membranes, and wherein the antimicrobial peptide has low mammalian cell toxicity when not linked to said tumor homing molecule. The present invention is based, in part, on the discovery that dimerization of endothelium-homing peptide monomer confers greatly increased cytotoxic activity on the conjugate. Based on this discovery, the invention further provides methods of inducing selective toxicity in vivo in an angiogenic endothelial tissue or cell type as well as methods of treating an individual having cancer by administering an effective amount of a homing conjugate of the invention also are provided.