Single wall nanotube constructs and uses therefor
The present invention provides soluble single wall nanotube constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble single wall carbon nanotube via a DNA or other oligomer platform attached to the single wall carbon nanotube. These soluble single wall carbon nanotube constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble single wall carbon nanotube constructs.
1. A method of treating a pathophysiological state in a subject, comprising:
administering a soluble single wall carbon nanotube (SWNT) construct functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereon, wherein the SWNT construct has a structure of SWNT-(DNA 1,2 -(cDNA 1 -peptide) m -(cDNA 2 -M*tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)) n ) x , such that cDNA 1 is linked to the peptide, cDNA 2 is linked to DOTA and DNA 1,2 is linked to the SWNT; and,
wherein cDNA 1 and cDNA 2 independently are non-identical oligomers and DNA 1,2 is an oligomer with a sequence complementary to cDNA 1 and cDNA 2 ; and,
wherein said DNA 1,2 is the sequence shown in SEQ ID NO: 1, said cDNA 1 is the sequence shown in SEQ ID NO: 2, and said cDNA 2 is the sequence shown in SEQ ID NO: 3; and,
wherein said peptide is an antibody or a targeting cyclic RGD or an NGR peptide ligand, M* is a radionuclide, x is 1 to 300; and m and n are independently 1 to 300; and
wherein, upon targeting cells associated with the pathophysiological state with said targeting moiety, said payload has a therapeutic effect against said cells or elicits a therapeutic effect from said cells thereby treating the pathophysiological state in the subject.
2. The method of claim 1 , wherein said antibody is rituximab, trastuzumab, or antinucleolin.
3. The method of claim 1 , wherein said radionuclide is actinium-225, astatine-211, indium-111, technetium-99, lutetium-177, gallium-68, holmium-166, bismuth-212, bismuth-213, yttrium-86, yttrium-90, copper-64, copper-67, samarium-117, samarium-153, iodine-123, iodine-124, iodine-125, or iodine-131.
4. The method of claim 1 , wherein the peptide is a targeting therapeutic antibody and the radionuclide is a diagnostic radionuclide, the method further comprising:
imaging a location of said therapeutic antibody after administering the soluble single wall carbon nanotube (SWNT) construct.
5. The method of claim 4 , wherein the therapeutic targeting antibody is rituximab and the diagnostic radionuclide is yttrium-86.
6. The method of claim 1 , wherein said cells associated with the pathophysiological state are cancer cells, vascular endothelial cells or activated T cells.