Carrier nanoparticles and related compositions, methods and systems

Patent metadata

Field	Value
Publication number	US-9610355-B2
Application number	US-201615137453-A
Country	US
Kind code	B2
Filing date	Apr 25, 2016
Priority date	Aug 13, 2008
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

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 and related compositions, methods and systems.

First claim

What is claimed is:

1. A polymer conjugate comprising a polymer containing a polyol and a polymer containing a phenylboronic acid,
wherein the polymer containing a phenylboronic acid is conjugated to the polymer containing a polyol with a reversible borate ester linkage, and
wherein the polymer containing the polyol is a product of coupling a compound of Formula A with a compound of Formula B;

wherein
the compound of Formula A is:

in which
the spacer is independently selected from any organic group;
the amino acid is selected from any organic group bearing a free amine and a free carboxylic acid group;
n is 1-20; and
Z 1 is independently selected from —NH 2 , —OH, —SH, and —COOH; and

the compound of Formula B is:

in which
q is a number from 1 to 20;
p is a number from 20 to 200; and
L is a leaving group.

2. The polymer conjugate of claim 1 , wherein A is:

wherein n is a number from 1 to 20.

3. The polymer conjugate of claim 1 , wherein compound of Formula B is:

4. The polymer conjugate of claim 3 , wherein the polymer containing the polyol comprises units of the formula:

5. The polymer conjugate of claim 4 , wherein n is 1 and q is 1.

6. The polymer conjugate of claim 1 , wherein compound of Formula B is:

7. The polymer conjugate of claim 6 , wherein the polymer containing the polyol comprises units of the formula:

8. The polymer conjugate of claim 7 , wherein n is 1 and p is 1.

9. The polymer conjugate of claim 1 , wherein the polymer containing a phenylboronic acid comprises at least one terminal phenylboronic acid group and has the general formula:

wherein
R 3 and R 4 are independently (CH 2 CH 2 O) t , where t is from 2 to 2000;
X 1 is —NH—C(═O)—, —S—S—, —C(═O)—NH—, —O—C(═O)— or —C(═O)—O—;
Y 1 is a phenyl group;
r=1; a=0; and b=1; and
wherein Functional group 1 and Functional group 2 independently comprise a —B(OH) 2 , —OCH 3 , —COOH, —NH 2 , or —OH group.

10. The polymer conjugate of claim 2 , wherein the polymer containing a phenylboronic acid comprises at least one terminal phenylboronic acid group and has the general formula:

wherein
R 3 and R 4 are independently (CH 2 CH 2 O) t , where t is from 2 to 2000;
X 1 is —NH—C(═O)—, —S—S—, —C(═O)—NH—, —O—C(═O)— or —C(═O)—O—;
Y 1 is a phenyl group;
r=1; a=0; and b=1; and

wherein Functional group 1 and Functional group 2 independently comprise a —B(OH) 2 , —OCH 3 , —COOH, —NH 2 , or —OH group.

11. The polymer conjugate of claim 9 , wherein Functional group 2 comprises a —B(OH) 2 , —OCH 3 , —OH, or —COOH group.

12. The polymer conjugate of claim 9 , wherein the polymer containing a phenylboronic acid is:

wherein t is a number from 200 to 300.

13. The polymer conjugate of claim 10 , wherein the polymer containing a phenylboronic acid is:

wherein t is a number from 2 to 2000.

14. The polymer conjugate of claim 9 , in which the polymer conjugate is in the form of a nanoparticle.

15. The polymer conjugate of claim 10 , in which the polymer conjugate is in the form of a nanoparticle.

16. The nanoparticle of claim 14 , further comprises a therapeutic agent.

17. The nanoparticle of claim 15 , further comprises a therapeutic agent.

18. The nanoparticle of claim 14 , further comprising a chemotherapeutic agent, a polynucleotide, a nucleotide, aptamers, polypeptide, protein, polysaccharide, antibody, or antibody fragment.

19. The nanoparticle of claim 15 , wherein the small molecule chemotherapeutic is camptothecin, an epothilone, taxol or a combination thereof.

20. The nanoparticle of claim 14 , wherein the phenylboronic acid that is coupled to the polymer containing a polyol with a reversible covalent linkage is further conjugated to at least one targeting ligand.

21. The nanoparticle of claim 15 , wherein the phenylboronic acid that is coupled to the polymer containing a polyol with a reversible covalent linkage is further conjugated to at least one targeting ligand, each targeting ligand being conjugated to the terminal portion of the polymer containing a phenylboronic acid.

22. The nanoparticle of claim 20 , wherein at least one of the targeting ligand is a protein, an monosaccharide, peptide, polysaccharide, a small molecule, or an antibody.

23. The nanoparticle of claim 21 , where the targeting ligand is folic acid.

24. The nanoparticle of claim 21 , wherein the targeting ligand is transferrin.

25. A method to deliver a therapeutic agent to a target, the method comprising contacting the target with the nanoparticle of claim 20 .

26. A method to deliver a therapeutic agent to a target, the method comprising contacting the target with the nanoparticle of claim 21 .

27. The method of claim 25 , wherein the target is a cancer cell within the body of a mammal.

28. The method of claim 26 , wherein the target is a cancer cell within the body of a mammal.

29. The nanoparticle of claim 20 , wherein the therapeutic agent is conjugated to the polymer containing the polyol.

30. The nanoparticle of claim 21 , wherein the therapeutic agent is conjugated to the polymer containing the polyol.

31. The nanoparticle of claim 20 , wherein the therapeutic agent is conjugated to the polymer containing the phenylboronic acid.

32. The nanoparticle of claim 21 , wherein the therapeutic agent is conjugated to the polymer containing the phenylboronic acid.

Assignees

• California Inst Of Techn

Inventors

• Davis Mark E
• Alabi Akinleye

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C12N2310/351

  Conjugate · CPC title

• C08G69/48

  Polymers modified by chemical after-treatment · CPC title