Method And Composition For The Treatment Of Cancer By The Enzymatic Conversion Of Soluble Radioactive Toxic Precipitates In The Cancer

Abstract

The invention features compositions and methods for treating or alleviating a symptom of cancer. The compositions and methods of the invention direct supra-lethal doses of radiation, called Hot-Spots, to virtually all cancer cell types.

1 . A reagent comprising a cell targeting agent which augments cellular uptake of the reagent linked to a platform building material, wherein said platform building material detaches from said cell targeting agent upon uptake of the reagent into the cell and forms an aqueous insoluble nano-platform. 
     
     
         2 . The reagent of  claim 1 , wherein said cell targeting agent is linked to the platform building material by a carrier moiety. 
     
     
         3 . The reagent of  claim 2 , wherein said carrier moiety is a protein, a polysaccharide, a polymer, a dendrimer, a liposome, a nanoparticle or a polymeric micelle. 
     
     
         4 . The reagent of  claim 3 , wherein said polymer is a synthetic polymer or a biopolymer. 
     
     
         5 . The reagent of  claim 4 , wherein said biopolymer is a polylysine. 
     
     
         6 . The reagent of  claim 1 , wherein said platform building material further comprises an additional molecular structure. 
     
     
         7 . The reagent of  claim 6 , wherein said additional molecular structure is capable of specifically binding a second reagent. 
     
     
         8 . The reagent of  claim 6 , wherein said additional molecular structure is a polypeptide, a peptide, a lectin, a small molecule or an organic functional group. 
     
     
         9 . The reagent of  claim 1 , wherein said cell targeting agent is a polypeptide, a cell surface ligand, a peptide or a small molecule. 
     
     
         10 . The reagent of  claim 9 , wherein said polypeptide is an antibody or fragment thereof. 
     
     
         11 . The reagent of  claim 10 , wherein said antibody is an EGF receptor antibody or a transferrin receptor antibody. 
     
     
         12 . The reagent of  claim 9 , wherein said polypeptide is a viral protein. 
     
     
         13 . The reagent of  claim 12 , wherein said viral protein is a human immunodeficiency virus (HIV) 1 TAT protein, a functionally effective portion of (HIV) 1 TAT protein, or VP22. 
     
     
         14 . The reagent of  claim 9 , wherein said cell surface ligand is transferrin, epidermal growth factor or an interleukin. 
     
     
         15 . The reagent of  claim 9 , wherein said peptide is a peptide hormone or an arginine-glycine-aspartic acid peptide. 
     
     
         16 . The reagent of  claim 15 , wherein said peptide hormone is oxytocin, growth hormone releasing hormone, glucagon, gastrin, secretin, somatostatin, prolactin, follicle stimulating hormone, insulin, or growth hormone. 
     
     
         17 . The reagent of  claim 9 , wherein said small molecule is a hormone, a nucleic acid, a peptidomimetic, a carbohydrate, a lipid, a nicotinic acetylcholine receptor agonist or folic acid or analogue or derivative thereof. 
     
     
         18 . The reagent of  claim 17 , wherein said hormone is estrogen, calciferol, or testosterone. 
     
     
         19 . The reagent of  claim 1 , wherein said platform building material is an indoxyl, a porphyrin, a polymer, a dendrimer, an opio-melanin or a polysaccharide. 
     
     
         20 . The reagent of  claim 19 , wherein said polymer is a HPMA derivative. 
     
     
         21 . The reagent of  claim 19 , wherein said polysaccharide is dextran, gum Arabic, cellulose or chitin. 
     
     
         22 . The reagent of  claim 19 , wherein said indoxyl is a substituted indoxyl. 
     
     
         23 . The reagent of  claim 22 , wherein said substituted indoxyl is a mono-indoxyl, a bis-indoxyl or a poly-indoxyl. 
     
     
         24 . The reagent of  claim 19 , wherein said indoxyl forms indigo, a linear indigo polymer or a polyindigo lattice. 
     
     
         25 . A reagent comprising a targeting moiety and an isotope-trapping moiety. 
     
     
         26 . The reagent of  claim 25 , wherein said targeting moiety is capable of binding to an aqueous insoluble nano-platform. 
     
     
         27 . The reagent of  claim 25 , wherein said targeting moiety is an organic functional group, a polypeptide, a peptide, or a lectin. 
     
     
         28 . The reagent of  claim 27 , wherein said polypeptide is an enzyme, an antibody or a fragment thereof. 
     
     
         29 . The reagent of  claim 28 , wherein said enzyme is a mutant enzyme. 
     
     
         30 . The reagent of  claim 29 , wherein said mutant enzyme is a mutant β-lactamase. 
     
     
         31 . The reagent of  claim 28 , wherein said enzyme is a β-lactamase, an arginine decarboxylase, an ornithine decarboxylase, a chloramphenicol acetyltransferase, or a UDP-N-acetylglucosamine enolpyruvoyltransferase. 
     
     
         32 . The reagent of  claim 27 , wherein said organic functional group is a hydrazide, a ketone, a mercaptan, or a maleimidyl. 
     
     
         33 . The reagent of  claim 25 , wherein said isotope trapping moiety is an organic functional group, a polypeptide, a peptide, or a lectin. 
     
     
         34 . The reagent of  claim 33 , wherein said polypeptide is an enzyme, an antibody or a fragment thereof. 
     
     
         35 . The reagent of  claim 34 , wherein said enzyme is a mutant enzyme. 
     
     
         36 . The reagent of  claim 35 , wherein said mutant enzyme is a mutant β-lactamase. 
     
     
         37 . The reagent of  claim 34 , wherein said enzyme is a β-lactamase, an arginine decarboxylase, an ornithine decarboxylase, a chloramphenicol acetyltransferase, UDP-N-acetylglucosamine enolpyruvoyltransferase, nitroreductase, glycosidases, carboxypeptidase A, alkaline phosphatase, or a sulfatase. 
     
     
         38 . The reagent of  claim 33 , wherein said organic functional group is a hydrazide, a ketone, a mercaptan, or a maleimidyl. 
     
     
         39 . A kit packaged in one or more containers comprising:
 a. a reagent comprising a cell targeting agent which augments cellular uptake of the reagent linked to a platform building material, wherein said platform building material detaches from said cell targeting agent upon uptake of the reagent into the cell and forms an aqueous insoluble nano-platform; and   b. a bi-specific reagent comprising a targeting moiety capable of binding to the aqueous insoluble nano-platform and an isotope trapping moiety.   
     
     
         40 . The kit of  claim 39 , further comprising a radiolabeled aqueous soluble reagent. 
     
     
         41 . The kit of  claim 39 , further comprising a cell-killing reagent. 
     
     
         42 . The kit of  claim 39 , wherein the reagent according to (a) further comprises an additional molecular structure. 
     
     
         43 . The kit of  claim 39 , wherein the targeting moiety according to (b) binds said additional molecular structure. 
     
     
         44 . A method of alleviating a symptom of cancer comprising administering to a subject suffering from said cancer:
 a. a reagent comprising a cell targeting agent which augments cellular uptake of the reagent linked to a platform building material, wherein said platform building material detaches from said cell targeting agent upon uptake of the reagent into the cell and forms an aqueous insoluble nano-platform;   b. a bi-specific reagent comprising a targeting moiety capable of binding to the aqueous insoluble nano-platform and an isotope trapping moiety; and   c. a radiolabeled aqueous soluble reagent.   
     
     
         45 . The method of  claim 44 , further comprising administering a cell-killing reagent prior to the administration of (b). 
     
     
         46 . The method of  claim 44 , further comprising administering a cell-killing reagent after the administration of (b). 
     
     
         47 . The method of  claim 44 , further comprising administering a cell-killing reagent concurrently with the administration of (b). 
     
     
         48 . The method of  claim 44 , wherein said cancer is breast cancer, skin cancer, prostate cancer, lung cancer, colon cancer, liver cancer, cervical cancer, brain cancer, ovarian cancer, pancreatic cancer, or stomach cancer.