Helical polycarbodiimide polymers and associated imaging, diagnostic, and therapeutic methods

Abstract

Described herein are suspensions of helical polycarbodiimide polymers that ‘cloak’ nanotubes, thereby effecting control over nanotube emission, providing a new mechanism of environmental responsivity, and enabling precise control over sub-cellular localization. The helical polycarbodiimide polymers described herein are water soluble, easily modifiable, and have unique architectures that facilitate their application in radiopharmaceutical delivery and imaging methods, in therapeutics and therapeutic delivery methods, and their use as sensors—both in conjunction with carbon nanotubes, and without nanotubes.

1 . A suspension of helical-polymer-encapsulated carbon nanotubes, wherein the helical polymer is a polycarbodiimide. 
     
     
         2 . The suspension of  claim 1 , wherein the carbon nanotubes are single-walled carbon nanotubes (SWCNTs). 
     
     
         3 . The suspension of  claim 1 , wherein the helical polymer comprises a clickable polymer scaffold. 
     
     
         4 . The suspension of  claim 1 , wherein the polycarbodiimide comprises one or more monomeric species selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         5 . The suspension of  claim 1 , wherein the suspension is an aqueous suspension. 
     
     
         6 . The suspension of  claim 1 , wherein at least a plurality of the helical-polymer-encapsulated carbon nanotubes in the suspension are in van der Waals contact at a center-to-center distance between adjacent nanotubes sufficient to exhibit inter-nanotube Förster resonance energy transfer (INFRET). 
     
     
         7 . The suspension of  claim 6 , wherein the center-to-center distance is from 1 nm to 4 nm. 
     
     
         8 . The suspension of  claim 6 , wherein the dispersed helical-polymer-encapsulated carbon nanotubes in van der Waals contact are not irreversibly bound. 
     
     
         9 . The suspension of  claim 6 , comprising (i) a first set of nanotubes each encapsulated by a helical polymer having at least a first substituent functional group, and (ii) a second set of nanotubes each encapsulated by a helical polymer having at least a second substituent functional group, wherein the first substituent functional group and the second substituent functional group imbue the first and second sets of encapsulated nanotubes with sufficiently strong coulombic attraction to each other to form reversible fluorescent aggregates in the suspension. 
     
     
         10 . The suspension of  claim 1 , wherein the helical polymer comprises functional side chains. 
     
     
         11 . The suspension of  claim 10 , wherein the functional side chains comprise one or more members selected from the group consisting of a primary amine, a carboxylic acid, a guanidine group, an oligoethylene glycol, a methoxy-polyethylene glycol (PEG), a hydroxyl-PEG, a folic acid, a trimethoprim, a peptide, an alkyne peptide, an adenosine triphosphate (ATP) peptide, and an opioid. 
     
     
         12 . The suspension of  claim 1 , wherein the helical polymer comprises one or more aromatic groups incorporated in its monomer substituents. 
     
     
         13 . The suspension of  claim 12 , wherein the one or more aromatic groups promote multi-valent π-π interactions between the polymer and the graphitic sidewall of the carbon nanotubes. 
     
     
         14 . The suspension of  claim 1 , wherein the functional side chains comprise a targeting group. 
     
     
         15 . A biomolecular imaging probe and/or sensor comprising the suspension of  claim 1 . 
     
     
         16 . An imaging method comprising:
 administering the suspension of  claim 1  to a biological sample;   exposing the biological sample comprising the administered suspension to excitation light; and   detecting light emitted by suspension or fluorescent aggregates formed by one or more components of the suspension.   
     
     
         17 . The method of  claim 16 , further comprising disrupting the fluorescent aggregates to reverse the emission of light. 
     
     
         18 . The method of  claim 17 , further comprising alternating between cycles of light emission and no light emission by re-aggregating and disrupting, respectively, the fluorescent aggregates for high resolution biomolecular imaging. 
     
     
         19 . The method of  claim 16 , wherein the detecting step comprises obtaining images of cellular nuclei of the biological sample. 
     
     
         20 . A method of treating a disease or disorder, the method comprising administering the suspension of  claim 1  to a subject, wherein the functional side chains of the helical polymer comprises a therapeutic. 
     
     
         21 . The method of  claim 20 , wherein the therapeutic comprises an opiate. 
     
     
         22 . A method for pretargeted radioimmunotherapy (PRIT), the method comprising administering a polycarbodiimide functionalized with an antibody, labeled with a radionuclide. 
     
     
         23 . The method of  claim 22 , wherein the radionuclide comprises a metallic lanthanide. 
     
     
         24 . The method of  claim 22 , wherein the radionuclide is attached to the polycarbodiimide via a chelator. 
     
     
         25 . The method of  claim 22 , wherein the radionuclide comprises  89 Zr. 
     
     
         26 . The suspension of  claim 1 , wherein the suspension is a stable suspension in aqueous solution or in serum. 
     
     
         27 - 71 . (canceled)