NOVEL CURCUMINOID-FACTOR VIIA CONSTRUCTS AS SUPPRESSORS OF TUMOR GROWTH AND ANGIOGENESIS

摘要

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 involve s 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. The present invention furth er provides for the synthesis of novel curcuminoid-tether-linker-factor VIIa compositions and for methods of delivery of effective doses of the novel compositions to target tumor or endothelial cells in a patient.