Carrier nanoparticles and related compositions, methods and systems

Patent metadata

Field	Value
Publication number	US-9334367-B2
Application number	US-201514805831-A
Country	US
Kind code	B2
Filing date	Jul 22, 2015
Priority date	Aug 13, 2008
Publication date	May 10, 2016
Grant date	May 10, 2016

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 nanoparticle comprising a polyol-containing polymer, a boronic acid-containing polymer, and at least one targeting ligand molecule;
wherein the boronic acid-containing polymer having a structure of 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)—, —C(═O)—NH—CH 2 —, —C(═O)—NH—, —S—S—, —O—C(═O)— or —C(═O)—O—;
Y 1 is an alkylene with a carbon number of at least 1 or is an aromatic group;
Functional group 2 independently comprises —OCH 3 , —OH, —B(OH) 2 , —COOH, —NH 2 , or —(X 1 )—(Y 1 )—B(OH) 2 ;
r is 1;
a is 0; and
b is 1; and
said boronic acid-containing polymer being coupled to the polyol-containing polymer with reversible borate ester linkages formed between the —B(OH) 2 of the boronic acid-containing polymer and vicinal diols of the polyol-containing polymer;
said targeted nanoparticle being configured to present the boronic acid-containing polymer to an environment external to the nanoparticle; and
wherein the boronic acid-containing polymer is conjugated to the at least one targeting ligand molecule by coupling with the or Functional group 2.

2. The nanoparticle of claim 1 , wherein the polyol-containing polymer comprises mucic acid.

3. The nanoparticle of claim 1 , wherein the polyol-containing polymer further comprises polyethylene glycol linkages of formula:

where n is where n is from 1 to 20 at each occurrence.

4. The nanoparticle of claim 1 , wherein the polyol-containing polymer further comprises amidines groups, primary amine groups, secondary amine groups, tertiary amine groups, imidazolium groups, or protonated derivatives thereof.

5. The nanoparticle of claim 1 , wherein the polyol-containing polymer comprises mucic acid, polyethylene glycol linkages having 1 to 20 ethylene glycol moieties, and protonated amidine groups.

6. The nanoparticle of claim 1 , wherein Y 1 is phenyl.

7. The nanoparticle of claim 1 , wherein t is from 100 to 300.

8. The nanoparticle of claim 1 , wherein Functional group 2 independently comprises —COOH, —NH 2 , —OH, or —B(OH) 2 .

9. The nanoparticle of claim 1 wherein:
the polyol-containing polymer comprises mucic acid, polyethylene glycol linkages having 1 to 20 ethylene glycol moieties, and protonated amidine groups;
Y 1 is phenyl;
t is 20 to 300; and
Functional group 2 comprises —OH, —B(OH) 2 , —COOH, or —NH 2 .

10. The nanoparticle of claim 9 , wherein the nanoparticle is coupled to more than one targeting ligand molecules per nanoparticle.

11. The nanoparticle of claim 10 , wherein the targeting ligand molecule comprises an antibody, an antibody fragment, transferrin, folic acid, 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.

12. The nanoparticle of claim 10 , wherein the targeting ligand molecule comprises a small molecule, protein, protein fragment, peptide, full antibody, antibody fragment, monosaccharide, polysaccharide, nucleotide, or polynucleotide.

13. The nanoparticle of claim 10 , further comprising a therapeutic agent incorporated therein or coupled thereto.

14. The nanoparticle of claim 13 , wherein the therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

15. The nanoparticle of claim 13 , wherein the therapeutic agent is genomic DNA, cDNA, mRNA, siRNA, shRNA, miRNA, an antisense oligonucleotide, a viruses, or a chimeric polynucleotide.

16. The nanoparticle of claim 15 , wherein the therapeutic agent is an interfering RNA.

17. The nanoparticle of claim 13 , wherein the therapeutic agent comprises camptothecin, doxorubicin, or taxol.

18. An aqueous solution or dispersion of a plurality of nanoparticles of claim 10 .

19. The aqueous solution of dispersion of claim 18 , wherein each nanoparticle further comprises a therapeutic agent incorporated therein or coupled thereto.

20. The aqueous solution of dispersion of claim 19 , wherein therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

21. The aqueous solution of dispersion of claim 19 , wherein therapeutic agent is an interfering RNA.

22. The nanoparticle of claim 9 , wherein the nanoparticle is coupled to one targeting ligand molecule per nanoparticle.

23. The nanoparticle of claim 22 , wherein the targeting ligand molecule comprises an antibody, an antibody fragment, transferrin, folic acid, 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.

24. The nanoparticle of claim 22 , wherein the targeting ligand molecule comprises a small molecule, protein, protein fragment, peptide, full antibody, antibody fragment, monosaccharide, polysaccharide, nucleotide, or polynucleotide.

25. The nanoparticle of claim 22 , further comprising a therapeutic agent incorporated therein or coupled thereto.

26. The nanoparticle of claim 22 , wherein the therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

27. The nanoparticle of claim 25 , wherein the therapeutic agent is genomic DNA, cDNA, mRNA, siRNA, shRNA, miRNA, an antisense oligonucleotide, a viruses, or a chimeric polynucleotide.

28. The nanoparticle of claim 25 , wherein the therapeutic agent is an interfering RNA.

29. The nanoparticle of claim 25 , wherein the therapeutic agent comprises camptothecin, doxorubicin, or taxol.

30. An aqueous solution or dispersion of a plurality of nanoparticles of claim 22 .

31. The aqueous solution of dispersion of claim 30 , wherein each nanoparticle further comprises a therapeutic agent incorporated therein or coupled thereto.

32. The aqueous solution of dispersion of claim 30 , wherein therapeutic agent is a small molecule chemotherapeutic agent or a polynucleotide.

33. The aqueous solution of dispersion of claim 30 , wherein therapeutic agent is an interfering RNA.

Assignees

• California Inst Of Techn

Inventors

• Davis Mark E
• Alabi Akinleye

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K49/00

  Preparations for testing in vivo · CPC title