Single wall nanotube constructs and uses thereof
The present invention provides soluble single wall nanotube (SWNT) 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 SWNT via a DNA or other oligomer platform attached to the SWNT. These soluble SWNT 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 SWNT constructs.
1. A soluble SWNT construct having the structure SWNT-(DNA 1,2 (cDNA 1 -peptide) m -(cDNA 2 -M*tetraazacyclododecane-1,4,7,10-tetra acetic 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 or a contrast agent, x is 1 to 300; and m and n are independently 1 to 300.
2. The soluble SWNT of claim 1 , wherein said antibody is rituximab, trastuzumab, or antinucleolin.
3. The soluble SWNT of claim 1 , wherein said M* 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 soluble SWNT of claim 1 , wherein M* is a diagnostic radionuclide yttrium-86 or indium-111 or a gadolinium contrast agent.
5. The soluble SWNT of claim 1 having the structure SWNT-(DNA 1,2 -(cDNA 1 -rituximab) m -(cDNA 2 - 86 Y-tetraazacyclododecane-1,4,7,10-tetra acetic acid (DOTA) n ) x .
6. A method of locating or diagnosing a cancer in a subject, comprising:
administering the soluble SWNT construct of claim 1 to the subject, wherein said peptide is a targeting antibody or other targeting cyclic RGD or an NGR peptide ligand and M* is a diagnostic radionuclide or contrast agent; wherein, upon targeting cells comprising the cancer with the peptide and localizing the radionuclide or contrast agent thereto, the cancer cells are detectable in the subject, thereby locating or diagnosing the cancer.