Targeted Self-Assembly of Functionalized Carbon Nanotubes on Tumors

Abstract

Provided herein are single wall nanotube constructs to which are convalently linked a plurality of a bifunctional chelator, a therapeutic or a diagnostic radionuclide chelated to each bifunctional chelator and a plurality of morpholino oligonucleotides conjugated to the single wall nanotube. Also provided are single wall nanotube complexes which have the morpholino oligonucleotides on the single wall nanotube constructs hybridized to other morpholino oligonucleotides. The other morpholino oligonucleotides are each conjugated to a therapeutic antibody.

What is claimed is: 
     
         1 . A single wall nanotube construct, comprising:
 a plurality of a bifunctional chelator covalently linked to a single wall nanotube;   a therapeutic or a diagnostic radionuclide chelated to each bifunctional chelator; and   a plurality of morpholino oligonucleotides conjugated to the single wall nanotube.   
     
     
         2 . The single wall nanotube construct of  claim 1 , wherein each of the plurality of morpholino oligonucleotides has a sequence consisting of SEQ ID NO: 2. 
     
     
         3 . The single wall nanotube construct of  claim 2 , wherein each of the plurality of morpholino oligonucleotides is complementary to a morpholino oligonucleotide sequence consisting of SEQ ID NO: 1. 
     
     
         4 . The single wall nanotube construct of  claim 1 , wherein the bifunctional chelator is (4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid or diethylenetriaminepentaacetic acid (DTPA). 
     
     
         5 . The single wall nanotube construct of  claim 1 , wherein the therapeutic radionuclide is actinium-225, astatine-211, technetium-99, lutetium-177, gallium-68, holmium-166, bismuth-212, bismuth-213, yttrium-90, copper-67, samarium-117, samarium-153, iodine-123, or iodine-131. 
     
     
         6 . The single wall nanotube construct of  claim 5 , wherein the therapeutic radionuclide is actinium-225. 
     
     
         7 . The single wall nanotube construct of  claim 1 , wherein the diagnostic radionuclide is indium-111, yttrium-86, copper-64, iodine-124, iodine-125, or iodine-131. 
     
     
         8 . The single wall nanotube construct of  claim 1 , wherein the construct is soluble. 
     
     
         9 . A single wall nanotube complex, comprising:
 the single wall nanotube complex of  claim 1 ; and   a plurality of other morpholino oligonucleotides each conjugated to a therapeutic antibody and hybridized to one of the plurality of morpholino oligonucleotides comprising the single wall nanotube complex.   
     
     
         10 . The single wall nanotube complex of  claim 9 , wherein each of the plurality of morpholino oligonucleotides has a sequence consisting of SEQ ID NO: 1. 
     
     
         11 . The single wall nanotube complex of  claim 10 , wherein the therapeutic antibody is a monoclonal antibody. 
     
     
         12 . The single wall nanotube complex of  claim 11 , wherein the monoclonal antibody is an anti-CD20, anti-CD33, or anti-A33 antibody or a single chain variable fragment (scFv) or fragment antigen-binding (Fab) fragment thereof. 
     
     
         13 . The single wall nanotube complex of  claim 9 , wherein the therapeutic antibody is selective for a cancer. 
     
     
         14 . The single wall nanotube complex of  claim 13 , wherein the cancer is a lymphoma, a leukemia or a colon cancer.