Targeted nanoparticles

Patent metadata

Field	Value
Publication number	US-9468681-B2
Application number	US-201313782458-A
Country	US
Kind code	B2
Filing date	Mar 1, 2013
Priority date	Mar 1, 2013
Publication date	Oct 18, 2016
Grant date	Oct 18, 2016

Abstract

Described herein are carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a boronic acid, configured to present the polymer containing a boronic acid to an environment external to the nanoparticle. Targeted versions of the described nanoparticles are also described, as are related compositions, methods and systems.

First claim

What is claimed:

1. A targeted nanoparticle comprising a mucic acid-containing polymer, a therapeutic agent, and a polymer containing a nitrophenylboronic acid, said nitrophenylboronic acid being coupled to the mucic acid-containing polymer with a reversible covalent linkage, said targeted nanoparticle being configured to present the polymer containing the nitrophenylboronic acid to an environment external to the targeted nanoparticle, wherein the polymer containing the nitrophenylboronic acid is conjugated to a targeting ligand at its terminal end opposite the targeted nanoparticle, wherein the targeted nanoparticle has one molecule of targeting ligand per targeting nanoparticle.

2. The targeted nanoparticle of claim 1 wherein the mucic acid-containing polymer contains structural units comprising

3. The targeted nanoparticle of claim 1 wherein the polymer containing a nitrophenylboronic acid is

wherein Functional group 2 comprises —B(OH) 2 , —OCH 3 , —OH, —COOH, aldehyde, amine, or azide, and
wherein s=20-300.

4. The targeted nanoparticle of claim 1 wherein the targeting ligand is an antibody, transferrin, a ligand for a cellular receptor, a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.

5. The targeted nanoparticle of claim 1 wherein the therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

6. The targeted nanoparticle of claim 5 , wherein the polynucleotide is interfering RNA.

7. The targeted nanoparticle of claim 5 , wherein the small molecule chemotherapeutic agent is selected from camptothecin, an epothilone, a taxane and a polynucleotide or any combination thereof.

8. The targeted nanoparticle of claim 2 wherein the therapeutic agent is any one of camptothecin, an epothilone, a taxane, a polynucleotide or any combination thereof; the polymer containing nitrophenylboronic acid is

wherein Functional group 2 comprises —B(OH) 2 , —OCH 3 , —OH, —COOH, aldehyde, amine, or azide, and
wherein s=20-300, and the targeting ligand comprises any one of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.

9. The targeted nanoparticle of claim 2 wherein the therapeutic agent is camptothecin, the polymer containing nitrophenylboronic acid is

wherein Functional group 2 comprises —B(OH) 2 , —OCH 3 , —OH, —COOH, aldehyde, amine, or azide, and
wherein s=20-300, and the targeting ligand comprises an antibody.

10. A method of producing a targeted nanoparticle comprising conjugating a nanoparticle comprising a polymer containing a polyol with a polymer containing a nitrophenylboronic acid and conjugating the polymer containing the nitrophenylboronic acid to a targeting ligand, wherein the resulting targeted nanoparticle has no more than one molecule of targeting ligand per targeting nanoparticle.

11. The method of claim 10 , wherein
a. the polymer containing a polyol has contains structural units comprising

b. the polymer containing a nitrophenylboronic acid is

wherein Functional group 2 comprises —B(OH) 2 , —OCH 3 , —OH, —COOH, aldehyde, amine, or azide, and
c. the targeting ligand is an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.

12. The method of claim 10 , wherein the targeted nanoparticle further comprises a small molecule chemotherapeutic agent selected from camptothecin, an epothilone, a taxane and a polynucleotide or any combination thereof.

13. A kit for producing a targeted nanoparticle comprising a targeted nanoparticle comprising a polymer containing a polyol, a polymer containing a nitrophenylboronic acid, a targeting ligand, and instructions for producing a targeted nanoparticle having no more than one molecule of targeting ligand per targeted nanoparticle.

14. The kit of claim 13 wherein,
a. the polymer containing a polyol comprising a structural of:

b. the polymer containing a nitrophenylboronic acid is

wherein Functional group 2 comprises —B(OH) 2 , —OCH 3 , —OH, —COOH, aldehyde, amine, or azide, and
c. the targeting ligand is an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.

15. The kit of claim 13 , further comprising a small molecule chemotherapeutic agent selected from camptothecin, an epothilone, a taxane and a polynucleotide or any combination thereof.

16. A composition comprising the targeted nanoparticle of claim 1 and a suitable vehicle and/or excipient.

17. The composition of claim 16 , wherein the composition is a pharmaceutical composition and the suitable vehicle and/or excipient is a pharmaceutically acceptable vehicle and/or excipient.

18. The composition of claim 17 , wherein the targeted nanoparticle further comprises 10 B as part of at least one polymer containing a nitrophenylboronic acid the composition being formulated for in vivo boron neutron activation therapy.

19. A method to deliver a therapeutic agent to a target, the method comprising contacting the target with the targeted nanoparticle of claim 1 .

20. The method of claim 19 , wherein the target is a cancer cell within the body of a mammal.

21. A system to deliver a therapeutic agent to a target, the system comprising at least one polymer containing a polyol and at least one polymer containing a nitrophenylboronic acid capable of reciprocal binding through a reversible covalent linkage, the at least one polymer containing a polyol and the at least one polymer containing a nitrophenylboronic acid to be assembled with the therapeutic agent in the targeted nanoparticle of claim 1 to be used to deliver the therapeutic agent to the target.

22. A method to administer a therapeutic agent to an individual, the method comprising administering to the individual the targeting nanoparticle of claim 1 comprising the therapeutic agent.

23. A system for administering a therapeutic agent to an individual, the system comprising at least one polymer containing a polyol and at least one polymer containing a nitrophenylboronic acid capable of reciprocal binding through a reversible covalent linkage, the at least one polymer containing a polyol and polymer contain

Assignees

• California Inst Of Techn

Inventors

• Davis Mark E
• Han Han

Classifications

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• A61K31/727

  Heparin; Heparan · CPC title

• A61K47/48215

  Human Necessities · mapped topic

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title