Silk-elastin like protein polymers for embolization and chemoembolization to treat cancer

Abstract

A chemoembolic agent is disclosed that includes an injectable, recombinantly synthesized silk-elastin like protein copolymer and one or more chemotherapeutic agents. Upon injection, the chemoembolic agent blocks the tumor vasculature, including the capillary bed, and may optionally release chemotherapeutic agents. The chemoembolic agent may be used to treat cancer, including hepatocellular carcinoma.

We claim: 
     
         1 . An injectable embolic agent comprising at least one silk-elastin like protein copolymer. 
     
     
         2 . An embolic agent according to  claim 1 , wherein the agent is a liquid at 18-23° C. and wherein the agent transforms to a cross-linked hydrogel at 37° C. 
     
     
         3 . An embolic agent according to  claim 1 , wherein the at least one silk-elastin like protein copolymer is produced using recombinant methods. 
     
     
         4 . An embolic agent according to  claim 1 , wherein the at least one silk-elastin like protein copolymer comprises one or more of 
       
         
           
                 
               
                   (SEQ ID NO: 3) 
                 
                   MDPVVLQRRDWENPGVTQLVRLAAHPPFASDPMGAGSGAG 
                 
                     
                 
                   AGS[(GVGVP) 4 GKGVP(GVGVP) 3 (GAGAGS) 4 ] 12 (GVGVP) 4 GKG 
                 
                     
                 
                   VP(GVGVP) 2 (GAGAGS) 2 GAMDPGRYQDLRSHHHHHH 
                 
                   and 
                 
                     
                 
                   (SEQ ID NO: 4) 
                 
                   MDPVVLQRRDWENPGVTQLNRLAAHPPFASDPM[GAGS(GA 
                 
                     
                 
                   GAGS) 2 (GVGVP) 4 GKGVP(GVGVP) 11 (GAGAGS) 5 GA] 6 GAMDP 
                 
                     
                 
                   GRYQDLRSHHHHHH. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . An embolic agent according to  claim 1 , wherein the at least one silk-elastin like protein copolymer comprises one or more matrix metalloprotease cleavage sites. 
     
     
         6 . An embolic agent according to  claim 2 , wherein the agent has a viscosity of equal to or less than 1000 cP at 18-23° C. 
     
     
         7 . An embolic agent according to  claim 2 , wherein the agent has a viscosity of equal to or less than 150 cP at 18-23° C. 
     
     
         8 . An embolic agent according to  claim 2 , wherein the stiffness of the cross-linked hydrogel is approximately at least approximately 1×10 5  Pa. 
     
     
         9 . An embolic agent according to  claim 1 , wherein the agent contains a contrast-agent. 
     
     
         10 . An injectable chemoembolic agent comprising at least one silk-elastin like protein copolymer and at least one chemotherapeutic agent. 
     
     
         11 . An injectable chemoembolic agent according to  claim 10 , wherein at least one chemotherapeutic agent comprises a biologic compound. 
     
     
         12 . An injectable chemoembolic agent according to  claim 10 , wherein the agent is a liquid at 18-23° C. and wherein the agent transforms to a cross-linked hydrogel at 37° C. 
     
     
         13 . An injectable chemoembolic agent according to  claim 10 , wherein the at least one silk-elastin-like protein copolymer is produced using recombinant methods. 
     
     
         14 . An injectable chemoembolic agent according to  claim 10 , wherein the at least one silk-elastin-like protein copolymer comprises one or more of 
       
         
           
                 
               
                   (SEQ ID NO: 3) 
                 
                   MDPVVLQRRDWENPGVTQLVRLAAHPPFASDPMGAGSGAG 
                 
                     
                 
                   AGS[(GVGVP) 4 GKGVP(GVGVP) 3 (GAGAGS) 4 ] 12 (GVGVP) 4 GKG 
                 
                     
                 
                   VP(GVGVP) 2 (GAGAGS) 2 GAMDPGRYQDLRSHHHHHH  
                 
                   and 
                 
                     
                 
                   (SEQ ID NO: 4) 
                 
                   MDPVVLQRRDWENPGVTQLNRLAAHPPFASDPM[GAGS(GA 
                 
                     
                 
                   GAGS) 2 (GVGVP) 4 GKGVP(GVGVP) 11 (GAGAGS) 5 GA] 6 GAMDP 
                 
                     
                 
                   GRYQDLRSHHHHHH. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         15 . An injectable chemoembolic agent according to  claim 10 , wherein the at least one silk-elastin-like protein copolymer comprises one or more matrix metalloprotease cleavage sites. 
     
     
         16 . An injectable chemoembolic agent according to  claim 12 , wherein the agent has a viscosity of equal to or less than 1000 cP at 18-23° C. 
     
     
         17 . An injectable chemoembolic agent according to  claim 12 , wherein the agent has a viscosity of equal to or less than 150 cP at 18-23° C. 
     
     
         18 . An injectable chemoembolic agent according to  claim 10 , wherein the stiffness of the cross-linked hydrogel is at least approximately 1×10 5  Pa. 
     
     
         19 . An injectable chemoembolic agent according to  claim 10 , wherein the at least one chemotherapeutic agent is effective in treating hepatocellular carcinoma. 
     
     
         20 . An injectable chemoembolic agent according to  claim 10 , wherein the at least one chemotherapeutic agent comprises one or more of a drug targeting vascular endothelial growth factor and vascular endothelial growth factor receptor.