Fluorescent conjugated polymers with a bodipy-based backbone and uses thereof

Patent metadata

Field	Value
Publication number	US-9623123-B2
Application number	US-201615217133-A
Country	US
Kind code	B2
Filing date	Jul 22, 2016
Priority date	Dec 23, 2008
Publication date	Apr 18, 2017
Grant date	Apr 18, 2017

Abstract

The present invention provides various fluorescent conjugated polymers with a BODIPY-based backbone. The invention also provides methods of using the polymers of the invention, such as for imaging and detection of cells, tumors, bacteria and viruses.

First claim

The invention claimed is:

1. A method of enhancing medical imaging comprising administering an effective amount of a polymer to a subject in need of medical imaging and obtaining an image, wherein the amount of the polymer is sufficient to enhance an image compared to an image obtained in absence of the polymer; wherein the polymer is according to formula (I):

wherein each -A- is independently selected from

or

wherein each -AR- is independently selected from arylene or heteroarylene;
wherein each R 3 is independently selected from R, alkyl, aryl or heteroaryl
wherein each R 2 and R 4 are independently selected from alkyl or H;
wherein each R 1 and R 5 are independently selected from hydrogen, alkyl,
or

wherein each R 0 is —F, —OR, —R, aryl, heteroaryl,

or

wherein each R is independently selected from —H, —(CH 2 ) m R 10 , —(CH 2 ) m COO(CH 2 ) p CH 3 , —(CH 2 ) m SO 3 Na, —(CH 2 ) m PO 3 Na, —(CH 2 ) m N(CH 3 ) 3 + Br − , —(CH 2 ) m COH(CH 2 ) p CH 3 , —(CH 2 ) m OR 10 , —(CH 2 )OR 8 , —CH 2 CH 2 (OCH 2 CH 2 ) m OR 10 , —CH 2 CH 2 (OCH 2 CH 2 ) m OR 8 , —CH 2 CH 2 (OCH 2 CH 2 ) m SR 8 , or

and
wherein each R 8 is independently selected from a carbohydrate residue;
and wherein each R 10 is independently selected from hydrogen, alkyl, heteroalkyl, hydroxy, amino, ammonic acid, thiol, carboxylic acid, nitrile, azide, ethynylene, halo, and tosylate;
wherein m is from 0 to 100;
wherein n is from 2 to 300 and
wherein p is from 0 to 20.

2. The method of claim 1 , wherein the image is deep-tissue image.

3. The method of claim 1 , wherein the image is of a tumor or a cancer cell.

4. The method of claim 3 , wherein the polymer is further functionalized with a cancer-homing peptide.

5. A method of detecting the presence of a target in a sample comprising contacting the sample with a polymer which binds to the target and detecting fluorescence of the polymer; wherein the polymer is according to formula (I):

wherein each -A- is independently selected from

or

wherein each -AR- is independently selected from arylene or heteroarylene;
wherein each R 3 is independently selected from R, alkyl, aryl or heteroaryl
wherein each R 2 and R 4 are independently selected from alkyl or H;
wherein each R 1 and R 5 are independently selected from hydrogen, alkyl,
or

wherein each R 0 is —F, —OR, —R, aryl, heteroaryl,

or

wherein each R is independently selected from —H, —(CH 2 ) m R 10 , —(CH 2 ) m COO(CH 2 ) p CH 3 , —(CH 2 ) m SO 3 Na, —(CH 2 ) m PO 3 Na, —(CH 2 ) m N(CH 3 ) 3 + Br − , —(CH 2 ) m COH(CH 2 ) p CH 3 , —(CH 2 ) m OR 10 , —(CH 2 )OR 8 , —CH 2 CH 2 (OCH 2 CH 2 ) m OR 10 , —CH 2 CH 2 (OCH 2 CH 2 ) m OR 8 , —CH 2 CH 2 (OCH 2 CH 2 ) m SR 8 , or

and
wherein each R 8 is independently selected from a carbohydrate residue;
and wherein each R 10 is independently selected from hydrogen, alkyl, heteroalkyl, hydroxy, amino, ammonic acid, thiol, carboxylic acid, nitrile, azide, ethynylene, halo, and tosylate;
wherein m is from 0 to 100;
wherein n is from 2 to 300 and
wherein p is from 0 to 20.

6. The method of claim 5 , wherein the sample is in a subject.

7. The method of claim 5 , wherein the target is selected from the group consisting of bacteria and viruses.

8. The method of claim 7 , wherein the target is influenza.

9. The method of claim 8 , wherein the target is human influenza.

10. The method of claim 7 , wherein the polymer is functionalized with α2,6-sialic acid.

11. The method of claim 8 , wherein the target is avian influenza.

12. The method of claim 11 , wherein the polymer is functionalized with α2,3-sialic acid.

13. The method of claim 7 , wherein the target is E. coli.

14. The method of claim 13 , wherein the polymer is functionalized with α-mannose.

15. The method of claim 7 , wherein the target is Clostridium spp.

16. The method of claim 15 , wherein the polymer is functionalized with β-lactosamine.

17. The method of claim 5 , wherein the target is a tumor or a cancer cell.

18. The method of claim 17 , wherein the polymer is functionalized with a cancer-homing peptide.

19. A method of monitoring drug delivery comprising administering a polymer to a subject and detecting fluorescence of the polymer in the subject, wherein the polymer is further functionalized with an active agent; wherein the polymer is according to formula (I):

wherein each -A- is independently selected from

or

wherein each -AR- is independently selected from arylene or heteroarylene;
wherein each R 3 is independently selected from R, alkyl, aryl or heteroaryl
wherein each R 2 and R 4 are independently selected from alkyl or H;
wherein each R 1 and R 5 are independently selected from hydrogen, alkyl,
or

wherein each R 0 is —F, —OR, —R, aryl, heteroaryl,

or

wherein each R is independently selected from —H, —(CH 2 ) m R 10 , —(CH 2 ) m COO(CH 2 ) p CH 3 , —(CH 2 ) m SO 3 Na, —(CH 2 ) m PO 3 Na, —(CH 2 ) m N(CH 3 ) 3 + Br − , —(CH 2 ) m COH(CH 2 ) p CH 3 , —(CH 2 ) m OR 10 , —(CH 2 )OR 8 , —CH 2 CH 2 (OCH 2 CH 2 ) m OR 10 , —CH 2 CH 2 (OCH 2 CH 2 ) m OR 8 , —CH 2 CH 2 (OCH 2 CH 2 ) m SR 8 , or

and
wherein eac

Assignees

• Univ Michigan Tech

Inventors

• Liu Haiying

Classifications

• G01N33/575

  for cancer · CPC title

• A61K49/0054 Primary

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title

• G01N2021/6439

  with indicators, stains, dyes, tags, labels, marks · CPC title

• G01N2333/33

  from Clostridium (G) · CPC title

• A61K31/74

  Synthetic polymeric materials · CPC title