Dendrimer compositions for use in angiography

1. A dendrimer of formula (I):

wherein,

X is a G2 to G10 poly(amidoamine) (PAMAM) dendrimer;

L 1 and L 2 are each independently C 1 -C 12 alkylenyl, C 2 -C 12 alkenylenyl, or C 2 -C 12 alkynylenyl;

Z is a fluorophore;

Y is an oxidative stress probe;

R 1 is hydrogen or alkyl;

n is an integer from 1 to 100;

p is an integer from 0 to 100; and

m is an integer from 1 to 4000.

2. The dendrimer of claim 1 , wherein

X is a G2 to G6 PAMAM dendrimer;

L 1 and L 2 are each independently C 1 -C 6 alkylenyl, C 2 -C 6 alkenylenyl, or C 2 -C 6 alkynylenyl;

n is an integer from 1 to 10;

p is an integer from 1 to 10; and

m is an integer from 1 to 250.

3. The dendrimer of claim 1 , wherein

L 1 and L 2 are each independently C 1 -C 6 alkylenyl;

n is an integer from 1 to 5; and

p is an integer from 1 to 5.

4. The dendrimer of claim 1 , wherein Y, at each occurrence, is independently selected from the group consisting of 7-ethyl-10-hydroxycamptothecin, 4-hydroxy-2-nonenal, nitrotyrosine, 8-hydroxy-2′-deoxyguanosine, malonaldehyde, and 8-isoprostane.

5. The dendrimer of claim 1 having formula (I-a):

wherein,

X is a G2 to G10 poly(amidoamine) (PAMAM) dendrimer;

L 1 and L 2 are each independently C 1 -C 12 alkylenyl, C 2 -C 12 alkenylenyl, or C 2 -C 12 alkynylenyl;

Z is a fluorophore;

n is an integer from 1 to 100; and

m is an integer from 1 to 4000.

6. The dendrimer of claim 5 , wherein:

X is a G2 to G6 PAMAM dendrimer;

L 1 and L 2 are each independently C 1 -C 6 alkylenyl, C 2 -C 6 alkenylenyl, or C 2 -C 6 alkynylenyl;

n is an integer from 1 to 10; and

m is an integer from 1 to 250.

7. The dendrimer of claim 1 , wherein:

L 1 and L 2 are each independently C 1 -C 6 alkylenyl; and

n is an integer from 1 to 5.

8. The dendrimer of claim 1 having formula (I-b):

wherein,

X is a G2 to G10 PAMAM dendrimer;

Z is a fluorophore;

n is an integer from 1 to 100; and

m is an integer from 1 to 4000.

9. The dendrimer of claim 8 , wherein

X is a G2 to G6 PAMAM dendrimer;

n is an integer from 1 to 10; and

m is an integer from 1 to 250.

10. The dendrimer of claim 1 , wherein

X is a G4 PAMAM dendrimer;

n is 2; and

m is 62.

11. The dendrimer of claim 1 , wherein Z, at each occurrence, is independently selected from the group consisting of indocyanine green, fluorescein isothiocyanate, boron-dipyrromethene, rhodamine, and rose Bengal.

12. The dendrimer of claim 1 , wherein the dendrimer is:

wherein X is a G4 PAMAM dendrimer.

13. The dendrimer of claim 1 , wherein the dendrimer has a diameter of from about 1 nm to about 20 nm.

14. The dendrimer of claim 1 , wherein between about 0.1% and about 20% of the terminal groups of the dendrimer are covalently linked to a fluorophore.

15. A method for performing angiography on a subject in need thereof, the method comprising:

administering a composition to the subject, the composition comprising the dendrimer of claim 1 ; and

observing and/or quantifying the fluorescence emitted in the subject's eye vasculature.

16. The method of claim 15 , wherein the subject has macular degeneration (AMD), retinitis pigmentosa, optic neuritis, infection, uveitis, sarcoid, sickle cell disease, retinal detachment, temporal arteritis, retinal ischemia, choroidal ischemia, choroidal ischemia, ischemic optic neuropathy, arteriosclerotic retinopathy, hypertensive retinopathy, retinal artery blockage, retinal vein blockage, hypotension, diabetic retinopathy, macular edema, choroidal neovascularization, or a combination thereof.

17. The method of claim 15 , wherein the composition comprises a first set of dendrimers having a size of between about 2 nm and about 8 nm and a second set of dendrimers having a size about 12 nm and about 20 nm.

18. The method of claim 15 , wherein administering the composition includes injecting the composition intravenously into the vasculature of the subject.

19. The method of claim 15 , wherein the composition is administered at a dosage of between about 0.1 mg/kg and about 20 mg/kg.

20. The method of claim 15 , wherein the method is performed over a period of between about 10 seconds and about 28 days.

21. The method of claim 15 , wherein the method comprises a single administration of the composition and is performed for at least 21 days.

22. The method of claim 15 , wherein the method further comprises performing optical coherence tomography (OCT) on the subject.

23. The method of claim 15 , wherein the method further comprises identifying diseased vasculature.

24. The method of claim 23 , wherein the method further comprises identifying the disease stage of the diseased vasculature.

25. The method of claim 15 , wherein the composition further comprises a pharmaceutical acceptable carrier.

26. The method of claim 15 , wherein the method further comprises identifying the subject as in need of treatment for an eye disease.

27. The method of claim 26 , wherein the method further comprises administering an effective amount of a therapeutic agent to the subject identified as in need of treatment for an eye disease.

28. The method of claim 27 , wherein the therapeutic agent comprises triamcinolone acetonide, methyl prednisone, dexamethasone, COX-2 inhibitors, gold compound anti-inflammatory agents, salicylate anti-inflammatory agents, N-acetyl cysteine, minocycline, aflibercept, rapamycin, anti-VEGF agents, or a combination thereof.

29. A pharmaceutical composition comprising the dendrimer of claim 1 ; and a pharmaceutical acceptable carrier.

30. An angiography kit comprising:

the pharmaceutical composition of claim 29 ; and

instructions for using the pharmaceutical composition in angiography.