Energy-activated targeted cancer therapy

Abstract

The present invention is drawn to delivery systems for administering a therapy to a target tissue or target composition in a mammalian subject, using an ultrasonic energy-activated targeted agent. The claimed energy-activated targeted therapy is useful in the treatment of specifically selected target tissues, such as vascular endothelial tissue, the abnormal vascular walls of tumors, solid tumors of the head and neck, tumors of the gastrointestinal tract, tumors of the liver, tumors of the breast, tumors of the prostate, tumors of the lung, nonsolid tumors, malignant cells of the hematopoietic and lymphoid tissue and other lesions in the vascular system or bone marrow, and tissue or cells related to autoimmune and inflammatory disease.

1 . An ultrasonic energy-activated targeted delivery system that is selectively targeted to a target tissue, comprising: 
 (a) an ultrasonic energy-activated agent that absorbs energy and destroys a target tissue to which it is bound; and    (b) a ligand conjugated to the ultrasonic energy-activated agent, the ligand binding to a receptor on the target tissue with specificity, so that binding of the ligand to a non-target tissue is minimized.    
     
     
         2 . The delivery system of  claim 1 , wherein the energy-activated agent comprises a prodrug.  
     
     
         3 . The delivery system of  claim 1 , wherein the ligand comprises an antibody that binds to the receptor.  
     
     
         4 . The delivery system of  claim 1 , wherein the receptor is selected from the group consisting of a vascular endothelium antigen, an antigen that is specific for an abnormal vascular wall of a tumor and an antigen that is specific for a non-vascular tumor tissue.  
     
     
         5 . The delivery system of  claim 1 , wherein the ligand is selected from the group consisting of a target-specific antibody, a target-specific antibody fragment, a target-specific peptide and a target-specific polymer.  
     
     
         6 . The delivery system of  claim 1 , wherein the ligand and the receptor comprise a binding pair selected from the group consisting of a biotin-streptavidin, a chemokine-chemokine receptor, a growth factor-growth factor receptor and an antigen-antibody.  
     
     
         7 . The delivery system of  claim 1 , wherein the ligand is a target-specific antibody specific to an antigen selected from the group consisting of tumor surface antigen, tumor endothelial antigen, non-tumor endothelial antigen and tumor vessel wall antigen.  
     
     
         8 . The delivery system of  claim 1 , wherein the target tissue is selected from the group consisting of a vascular endothelial tissue, an abnormal vascular wall of a tumor, a solid tumor in one of the head, the neck, the gastrointestinal tract, the liver, the breast, the prostate, and the lung, a nonsolid tumor, malignant cells in hematopoietic tissue, malignant cells in lymphoid tissue, lesions in a vascular system, diseased bone marrow, cells afflicted by an autoimmune disease and cells afflicted with an inflammatory disease.  
     
     
         9 . The delivery system of  claim 1 , wherein the agent is selected from the group consisting of indocyanine green, methylene blue, toluidine blue, aminolevulinic acid, phthalocyanines, porphyrins, purpurins, texaphyrins, chlorins, bacteriochlorins, merocyanines, psoralens, benzoporphyrin derivatives (BPD), porfimer sodium and protoporphyrin IX.  
     
     
         10 . The delivery system of  claim 1 , wherein the agent is selected from the group consisting of a gallium-porphyrin complex, protoporphyrin, hematoporphyrin, daunorubicin and adriamycin.  
     
     
         11 . An ultrasonic energy-activated targeted delivery system, comprising: 
 (a) an ultrasonic energy-activated agent that absorbs energy and destroys a target tissue to which it is bound;    (b) a liposome delivery system; and    (b) a ligand that binds to a receptor on a target tissue with specificity;    wherein the ligand is separately conjugated to the ultrasonic energy-activated agent and to the liposomes of the liposome delivery system to provide dual targeting of the agent to the target tissue.    
     
     
         12 . The delivery system of  claim 11 , wherein the energy-activated agent comprises a prodrug.  
     
     
         13 . The delivery system of  claim 11 , wherein the ligand comprises an antibody that binds to the receptor.  
     
     
         14 . The delivery system of  claim 11 , wherein the receptor is selected from the group consisting of a vascular endothelium antigen, an antigen that is specific for an abnormal vascular wall of a tumor and an antigen that is specific for a non-vascular tumor tissue.  
     
     
         15 . The delivery system of  claim 11 , wherein the ligand is selected from the group consisting of a target-specific antibody, a target-specific antibody fragment, a target-specific peptide and a target-specific polymer.  
     
     
         16 . The delivery system of  claim 11 , wherein the ligand and the receptor comprise a binding pair selected from the group consisting of a biotin-streptavidin, a chemokine-chemokine receptor, a growth factor-growth factor receptor and an antigen-antibody.  
     
     
         17 . The delivery system of  claim 11 , wherein the ligand is a target-specific antibody specific to an antigen selected from the group consisting of tumor surface antigen, tumor endothelial antigen, non-tumor endothelial antigen and tumor vessel wall antigen.  
     
     
         18 . The delivery system of  claim 11 , wherein the target tissue is selected from the group consisting of a vascular endothelial tissue, an abnormal vascular wall of a tumor, a solid tumor in one of the head, the neck, the gastrointestinal tract, the liver, the breast, the prostate, and the lung, a nonsolid tumor, malignant cells in hematopoietic tissue, malignant cells in lymphoid tissue, lesions in a vascular system, diseased bone marrow, cells afflicted by an autoimmune disease and cells afflicted with an inflammatory disease.  
     
     
         19 . The delivery system of  claim 11 , wherein the agent is selected from the group consisting of indocyanine green, methylene blue, toluidine blue, aminolevulinic acid, phthalocyanines, porphyrins, purpurins, texaphyrins, chlorins, bacteriochlorins, merocyanines, psoralens, benzoporphyrin derivatives (BPD), porfimer sodium and protoporphyrin IX.  
     
     
         20 . The delivery system of  claim 11 , wherein the agent is selected from the group consisting of a gallium-porphyrin complex, protoporphyrin, hematoporphyrin, daunorubicin and adriamycin.