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

a polymer and polymer technology, applied in the field of compositions comprising polycarbodiimide polymers, can solve the problems of limiting the ability to measure (e.g., via imaging) the kinetics of dynamic self-assembly and disassembly of photoluminescent nanotubes into live cell nuclei, and achieves the effects of convenient radiopharmaceutical delivery, convenient modification, and precise control of sub-cellular localization

Inactive Publication Date: 2016-03-10
MEMORIAL SLOAN KETTERING CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes a new type of polymer that can control the emission of nanotubes, allowing for better control over the environment and more precise localization within the body. These polymers are water-soluble, easy to modify, and have unique structures that make them useful in a variety of applications, such as delivering molecules and treating diseases. They can also be used to deliver radionuclides or radionuclide-chelating agents. Overall, this patent introduces a new technology for controlling nanotube emission and offers new possibilities for research and development.

Problems solved by technology

However, such uses require the ability to simultaneously modulate nanotube fluorescence and to biocompatibly derivatize the nanotube surface using noncovalent methods.
However, encapsulation with biopolymers can produce higher background signal (e.g., DNA can produce high oxidation current and subsequently higher background currents) or provide inadequate control of coating the nanotube and therefore affect optical response (e.g., protein denaturation in unfavorable conditions).
Moreover, the above-mentioned synthetic polymers do not provide controllable and / or tunable properties, which limit the ability to measure (e.g., via imaging) the kinetics of dynamic self-assembly and disassembly and translocation of photoluminescent nanotubes into live cell nuclei.

Method used

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

Examples

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example 1

Helical Polycarbodiimide Cloaking of Carbon Nanotubes

[0136]In the examples described herein, a platform of helical polycarbodiimide polymers was synthesized to ‘cloak’ the nanotubes which affected control over nanotube emission, provided a new mechanism of environmental responsivity, and enabled precise control over sub-cellular localization. The helical polymers exhibited ordered surface coverage on the nanotubes, allowed systematic modulation of nanotube optical properties, and produced up to 12-fold differences in photoluminescence efficiency. The polymers facilitated controllable and reversible inter-nanotube Förster resonance energy transfer, allowing kinetic measurements of dynamic self-assembly and disassembly. Tailored polycarbodiimide substituent groups also enabled sub-cellular targeting for imaging, including stable translocation of photoluminescent nanotubes within live cell nuclei.

[0137]Synthetic helical polymers mimic the basic structural motifs of vital biomolecules s...

example 2

Synthesis of Helical Polycarbodiimide Polymers, for Use in Therapeutic and Diagnostic Applications

[0149]A synthesis scheme and molecular structures for helical polycarbodiimide polymers described herein are presented in FIGS. 12A-12C.

[0150]For synthesis of urea derivatives, a primary amine compound (RNH2) (1.0 equiv) was diluted in anhydrous dichloromethane and added to an isocyanate compound (RNCO) (1.2 equiv) in dichloromethane, stirred at low temperature, and kept cold in an ice bath. The reaction mixture was stirred at room temperature or refluxed overnight until the completion of the reaction. The solvent was removed in a rotary evaporator and crude white solid was purified by recrystallization in ethanol at 4° C. and dried to obtain white crystalline solid.

[0151]For synthesis of carbodiimide monomers, triethyl amine (2.5 equiv) was added to a suspension of dibromotriphenylphosphorane (1.2 mol equiv) in dichloromethane at low temperature and the reaction mixture was stirred at ...

example 3

Nanoscale Sensors for Quantitative Redox Potential Measurement

[0155]Reduction potential (or Redox) is a physical concept used to measure the tendency of chemical compounds (couples) to transfer electrons during a reaction, and by extension the chemical potential energy in a system or couple. The direction, regulation, and capacity for cellular activity depends upon the state of these redox reactions, quantifiable with an electric potential voltage, for phenomena as diverse as energy production, biosynthesis, gene expression, signaling and detoxification. Redox Biology currently remains largely qualitative. Recent linkage between perturbations in redox state and cancerous transformation, cell growth and division, cell viability, drug efficacy, and numerous pathologies have increased interest in quantitative Redox Biology.

[0156]In certain embodiments, the compositions described herein allow for a Single-Walled Carbon Nanotube (SWCNT) based optical sensor for this purpose. Current art ...

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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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to and the benefit of, and incorporates herein by reference in its entirety, U.S. Provisional Patent Application No. 62 / 038,235.GOVERNMENT SUPPORT[0002]This work was supported by National Institutes of Health grant DP2-HD07569.FIELD OF THE INVENTION[0003]This invention relates generally to compositions comprising polycarbodiimide polymers, and related imaging, diagnostic, and therapeutic methods.BACKGROUND[0004]Carbon nanotubes have several features which demonstrate their potential for biomedical applications including cellular sensing and imaging. For example, carbon nanotubes can be metallic or semiconducting depending on their structure, which is due to the symmetry and unique electronic structure of graphene. Thus, the electronic structure and diameter of the carbon nanotube will determine the spectral characteristics seen in absorption, fluorescence, Raman scattering, etc. Moreover, the environmental...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K51/06A61K47/48A61K51/10A61K51/12C01B31/02G01N33/58
CPCA61K51/065C01B31/0253A61K47/48876G01N33/582A61K51/1251A61K51/1096A61K47/48192A61K47/59A61K47/6927C01B32/168G01N33/542G01N33/587
Inventor HELLER, DANIEL A.BUDHATHOKI-UPRETY, JANUKA
Owner MEMORIAL SLOAN KETTERING CANCER CENT
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