Functionalized chromophoric polymer dots and bioconjugates thereof

Patent metadata

Field	Value
Publication number	US-10191060-B2
Application number	US-201013508981-A
Country	US
Kind code	B2
Filing date	Nov 9, 2010
Priority date	Nov 9, 2009
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

Abstract

The present invention provides, among other aspects, functionalized chromophoric polymer dots comprising a hydrophobic core and a hydrophilic cap, and bioconjugates thereof. Also provided are improved methods for preparing functionalized chromophoric polymer dots. Methods for in vivo imaging and molecular labeling are also disclosed.

First claim

What is claimed is:

1. A functionalized chromophoric polymer dot (Pdot) comprising:
a core and a cap, wherein said core comprises a chromophoric polymer, and said cap comprises a functionalization agent bearing one or more reactive functional groups, with the proviso that less than 100% of the cap is an organo silicate and the proviso that said cap does not encapsulate said core.

2. The functionalized chromophoric polymer dot (Pdot) of claim 1 , having a hydrophobic core and a hydrophilic cap, the Pdot comprising:
(a) the chromophoric polymer; and
(b) an amphiphilic molecule, having a hydrophobic moiety and a hydrophilic moiety, the hydrophilic moiety attached to the one or more reactive functional groups,

wherein:
the chromophoric polymer is embedded within the hydrophobic core of the Pdot;
a hydrophobic portion of the amphiphilic molecule is embedded within the hydrophobic core of the Pdot;
the hydrophilic cap comprises a hydrophilic portion of the amphiphilic molecule; and
the reactive functional group is located in the hydrophilic cap.

3. The functionalized chromophoric polymer dot of claim 1 , wherein the polymer dot comprises a blend of chromophoric polymers.

4. The functionalized chromophoric polymer dot of claim 1 , wherein the chromophoric polymer is a semiconducting polymer.

5. The functionalized chromophoric polymer dot of claim 4 , wherein the polymer dot comprises a blend of semiconducting polymers.

6. The functionalized chromophoric polymer dot of claim 5 , wherein the blend of semiconducting polymers includes a fluorene-benzothiadiazole-thiophen semiconducting polymer.

7. The functionalized chromophoric polymer dot of claim 2 , wherein the weight ratio of the amphiphilic molecule to chromophoric polymer is from about 1% to about 50%.

8. The functionalized chromophoric polymer dot of claim 7 , wherein the weight ratio of the amphiphilic molecule to chromophoric polymer is from about 5% to about 25%.

9. The functionalized chromophoric polymer dot of claim 2 , wherein the hydrophilic moiety of the amphiphilic molecule comprises a polyalkylene glycol.

10. The functionalized chromophoric polymer dot of claim 9 , wherein the polyalkylene glycol is a polyethylene glycol.

11. The functionalized chromophoric polymer dot of claim 2 , wherein the amphiphilic molecule is an amphiphilic polymer.

12. The functionalized chromophoric polymer dot of claim 11 , wherein the amphiphilic polymer is an amphiphilic, comb-like polymer.

13. The functionalized chromophoric polymer dot of claim 11 , wherein the amphiphilic polymer is a polyethylene glycol-grafted polystyrene.

14. The functionalized chromophoric polymer dot of claim 13 , wherein the polyethylene glycol moiety of the amphiphilic polymer is attached to one or more carboxyl groups.

15. The functionalized chromophoric polymer dot of claim 11 , wherein the amphiphilic polymer is a poly(styrene-co-maleic anhydride).

16. The functionalized chromophoric polymer dot of claim 11 , wherein the amphiphilic polymer is a semiconducting polymer.

17. The functionalized chromophoric polymer dot of claim 11 , wherein the amphiphilic polymer is a non-semiconducting polymer.

18. The functionalized chromophoric polymer dot of claim 2 , wherein the hydrophilic moiety of the amphiphilic polymer is attached to more than one reactive functional group.

19. The functionalized chromophoric polymer dot of claim 1 , wherein the one or more reactive functional group is selected from the group consisting of a carboxyl, amino, mercapto, azido, alkyne, aldehyde, hydroxyl, carbonyl, sulfate, sulfonate, phosphate, cyanate, succinimidyl ester, strained alkyne, azide, diene, alkene, tetrazine, strained alkene, cyclooctyne, phosphine groups, and any derivative thereof.

20. The functionalized chromophoric polymer dot of claim 19 , wherein the one or more reactive functional group is an alkyne, azido, strained alkyne, diene, alkene, tetrazine, strained alkene, cyclooctyne, phosphine or other moiety capable of being conjugated to a molecule via a bioorthogonal reaction.

21. The functionalized chromophoric polymer dot of claim 20 , wherein the bioorthogonal reaction is a click chemistry reaction.

22. The functionalized chromophoric polymer dot of claim 1 , wherein a biological molecule is conjugated to a reactive functional group on the surface of the polymer dot.

23. The functionalized chromophoric polymer dot of claim 22 , wherein the biological molecule comprises a molecule selected from the group consisting of a synthetic or naturally occurring protein, a glycoprotein, a polypeptide, an amino acid, a nucleic acid, a carbohydrate, a lipid, a fatty acid, and any combination thereof.

24. The functionalized chromophoric polymer dot of claim 23 , wherein the biological molecule is a polypeptide, an antibody, an aptamer, or a nucleic acid.

25. The functionalized chromophoric polymer dot of claim 1 , wherein the polymer dot is further conjugated to one or more non-reactive chemical groups.

26. The functionalized chromophoric polymer dot of claim 25 , wherein the non-reactive chemical group is a water soluble polymer.

27. The functionalized chromophoric polymer dot of claim 26 , wherein the water soluble polymer is polyethylene glycol.

28. The functionalized chromophoric polymer dot of claim 1 , further comprising an optically inactive polymer chemically cross-linked to the core.

29. The functionalized chromophoric polymer dot of claim 1 , further comprising a second chromophoric polymer chemically cross-linked to the core.

30. The functionalized chromophoric polymer dot of claim 28 , comprising an optically inactive polymer chemically cross-linked to the chromophoric polymer, wherein the chromophoric polymer is a semiconducting polymer.

31. The functionalized chromophoric polymer dot of claim 28 , wherein the optically inactive polymer is an amphiphilic polymer.

32. The functionalized chromophoric polymer dot of claim 28 , wherein the optically inactive polymer comprises a functional group suitable for conjugation to a biological molecule.

33. The functionalized chromophoric polymer dot of claim 32 , further comprising a biological molecule conjugated to the chromophoric polymer dot, wherein:
the biological molecule comprises an amine group;
the functional group is a carboxyl group; and
the amine group is cross-linked to the carboxyl group.

34. The functionalized chromophoric polymer dot of claim 31 , wherein the amphiphilic polymer is a semiconducting polymer.

35. The functionalized chromophoric polymer dot of claim 31 , wherein the amphiphilic polymer comprises a hydrophilic moiety, and wherein the hydrophilic moiety of the amphiphilic polymer is attached to more than one reactive functional group.

36. A functionalized chromophoric polymer dot (Pdot) comprising:
a hydrophobic core comprising a chromophoric polymer; and
a hydrophilic cap, comprising a functionalization agent bearing one or more reactive functional groups,
wherein at least a portion of an exterior surface of the functionalized chromophoric polymer dot is a surface of said hydrophobic core, with the proviso that less than 100% of the cap is an organo silicate.

37. The functionalized

Assignees

• Chiu Daniel T
• Wu Changfeng
• Mcneill Jason
• Yu Jiangbo
• Univ Washington
• Clemson Univeristy

Inventors

• Chiu Daniel T
• Wu Changfeng
• Mcneill Jason
• Yu Jiangbo

Classifications

• C09K11/06

  containing organic luminescent materials · CPC title

• G01N33/587 Primary

  Nanoparticles · CPC title

• C08L65/00 Primary

  Compositions of macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain (C08L7/00 - C08L57/00, C08L61/00 take precedence); Compositions of derivatives of such polymers · CPC title

• C09K2211/1483

  containing nitrogen and sulfur as heteroatoms · CPC title

• G01N33/582

  with fluorescent label · CPC title