Abstract: The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. The present invention provides methods to deliver a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors. The method involves tethering the drug to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage.

Abstract: Compositions and methods are provided for delivering cytotoxic compounds, such as natural curcumoids and synthetic curcumin analogs, specifically to cancer cells and to blood vessels that nourish solid tumors. The compositions include a cytotoxic drug tethered to a protein, such as factor VIIa, which can bind with high affinity to a receptor, such as tissue factor, expressed on the surface of cancer cells and vascular endothelial cells within the tumor microenvironment. Upon binding, the drug-protein-receptor complex is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage. The compositions and methods may increase the efficacy of the cytotoxic agets and decrease their side effects by delivering the agents to specific target cells, such as cancer cells, vascular endothelial cells in a tumor, and metastatic foci anywhere in the body, providing the target cells express surface bound tissue factor.

Abstract: The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. The present invention provides methods to deliver a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors. The method involves tethering the drug to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage.