Multifunctional nanoplatforms for fluorescence imaging and photodynamic therapy developed by post-loading photosensitizer and fluorophore to polyacrylamide nanoparticles

Patent metadata

Field	Value
Publication number	US-10568963-B2
Application number	US-201213566411-A
Country	US
Kind code	B2
Filing date	Aug 3, 2012
Priority date	Oct 21, 2009
Publication date	Feb 25, 2020
Grant date	Feb 25, 2020

Abstract

A composition comprising PAA nanoparticles containing a post loaded tetrapyrollic photosensitizer and a postloaded imaging agent and methods for making and using same.

First claim

What is claimed is:

1. A composition comprising a plurality of polyacrylamide nanoparticles, at least some of said nanoparticles having a tetrapyrollic photosensitizer for photodynamic therapy postloaded onto the nanoparticle after nanoparticle formation, and at least some of said nanoparticles containing an imaging agent, said tetrapyrollic photosensitizer having the structural formula:

R 1 and R 2 are each independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, —C(O)R a or —COOR a or —CH(CH 3 )(OR a ) or —CH(CH 3 )(O(CH 2 ) n XR a ) where R a is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted cycloalkyl; where R 2 may be —CH═CH 2 , —CH(OR 20 )CH 3 , —C(O)Me, —C(NR 21 )CH 3 or —CH(NHR 21 )CH 3
where X is an aryl or heteroaryl group;
n is an integer of 0 to 6;
where R 20 is methyl, butyl, heptyl, docecyl or 3,5-bis(trifluoromethyl)-benzyl; and
R 21 is 3,5,-bis(trifluoromethyl)benzyl;
R 1a and R 2a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;
R 3 and R 4 are each independently hydrogen or substituted or unsubstituted alkyl;
R 3a and R 4a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;
R 5 is hydrogen or substituted or unsubstituted alkyl;
R 6 and R 6a are each independently hydrogen or substituted or unsubstituted alkyl, or together form ═O;
R 7 is a covalent bond, alkylene, azaalkyl, or azaaraalkyl or ═NR 20 where R 20 in ═NR 20 is 3,5-bis(tri-fluoromethyl)benzyl or —CH 2 X—R 1 or —YR 1 where Y is an aryl or heteroaryl group;
R 8 and R 8a are each independently hydrogen or substituted or unsubstituted alkyl or together form ═O;
R 9 and R 10 are each independently hydrogen, or substituted or unsubstituted alkyl and R 9 may be —CH 2 CH 2 COOR 2 where R 2 is an alkyl group that may optionally substituted with one or more fluorine atoms;
each of R 1 -R 10 , when substituted, is substituted with one or more substituents each independently selected from Q, where Q is alkyl, haloalkyl, halo, or —COOR b where R b is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, araalkyl, or OR c where R c is hydrogen, alkyl, allkenyl, alkynyl, cycloalkyl, or aryl or CONR d R e where R d and R e are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or NR f R g where R f and R g are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or ═NR h where R h is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or is an amino acid residue;
each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Q 1 , where Q 1 is alkyl, haloalkyl, halo, or —COOR b where R b is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, araalkyl, or OR c where R c is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl or CONR d R e where R d and R e are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or NR f R g where R f and R g are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or ═NR h where R h is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl, or is an amino acid residue.

2. The composition of claim 1 wherein the imaging agent is a cyanine dye.

3. The composition of claim 2 wherein the cyanine dye is postloaded onto the nanoparticle after nanoparticle formation.

4. The composition of claim 1 wherein the imaging agent is a 124 I labeled compound.

5. The composition of claim 1 wherein the imaging agent is a PET, fluorescence or MR imaging agent.

6. The composition of claim 1 wherein at least some of the nanoparticles contain a targeting moiety.

7. The composition of claim 6 wherein the targeting moiety is a peptide, folic acid or a carbohydrate.

8. The composition of claim 2 where the cyanine dye is conjugated with the nanoparticle.

9. The composition of claim 1 where the photosensitizer is

purpurinimide having an absorbance between 680 and 720 nm, bacteriopurpurinimide having an absorbance between 780 and 800 nm or mixtures thereof.

10. The composition of claim 2 where the numerical ratio of postloaded photosensitizer moieties to cyanine dye moieties is from 1 to 1 to 10 to 1.

11. The composition of claim 10 where the numerical ratio of postloaded photosensitizer moieties to cyanine dye moieties is from 2 to 1 to 4 to 1.

12. The composition of claim 2 where the cyanine dye has the structural formula:

13. The composition of claim 1 where the photosensitizer is

14. The composition of claim 1 comprising a mixture of different nanoparticles, at least one of which contains a posdtloaded photosensitizer and at least one of which contains a postloaded cyanine dye.

15. The composition of claim 14 wherein the photosensitizer is

a purpurinimide having an absorbance between 680 and 720 nm, bacteriopurpurinimide having an absorbance between 780 and 800 nm or mixtures thereof.

16. A composition according to claim 1 comprising polyacrylamide nanoparticles, containing a tetrapyrollic photosensitizer postloaded to the nanoparticles after nanoparticle formation and an imaging agent covalently bonded to the nanoparticles and a tumor targeting moiety covalently bonded to the nanoparticles.

17. The composition of claim 16 wherein the photosensitizer is a pyropheophorbide-a, a purpurinimide, or a bacteriopurpurinimde.

18. The composition of claim 16 wherein the imaging agent is a cyanine dye.

19. The composition of claim 16 wherein the imaging agent is a 124 I labeled compound.

20. The composition of claim 16 wherein the imaging agent is a PET, fluorescence or MR imaging agent.

21. The composition of claim 16 wherein the targeting moiety is selected from the group consisting of ROD and F3-Cys peptide.

22. The composition of claim 6 where the targeting moiety is a tumor targeting moiety selected from the group consisting of an RGD and F3-Cys peptide.

23. Polyacrylamide nanoparticles according to claim 1 wherein the photosensitizer is selected from the group consisting of pyropheophorbides, purpurinimides and bacteriopurpurinimides and tetrapyrollic derivatives thereof.

24. Nanoparticles according to claim 23 where the imaging agent is selected from the group consisting of a cyanine dye, an 124 I labeled compound, a PET, fluorescence and MR imaging agent.

25. Nanoparticles according to claim 24 where the nanoparticles further comprise a tumor-targeting moiety.

26. Nanoparticles according to claim 25 where the tumor targeting moiety is selected from the group consisting of pe

Assignees

• Pandey Ravindra K
• Kopelman Raoul
• Gupta Anurag
• Sajjad Munawwar
• Health Research Inc
• He Research Foundation Of State Univ Of New York
• Univ Michigan

Inventors

• Pandey Ravindra K
• Kopelman Raoul
• Gupta Anurag
• Sajjad Munawwar

Classifications

• B82Y15/00

  Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors · CPC title

• A61K41/0057 Primary

  Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent · CPC title

• A61K41/0071

  PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines · CPC title

• A61K47/6933

  the polymer being obtained by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol · CPC title

• A61K51/0451

  having four such rings, e.g. phorphine derivatives, bilirubin, biliverdine (hemin, hematin A61K51/0472) · CPC title