Compositions and methods for diagnosing or treating neutrophil-mediated inflammatory disease
Disclosed are nanoparticle compositions comprising nanoparticles prepared from denatured, cross-linked albumin and a therapeutic agent for treating a neutrophil-mediated inflammation, and methods of treating neutrophil-mediated inflammation using the compositions.
1. A method of delivering an agent to activated neutrophils comprising contacting the activated neutrophils with nanoparticles, each nanoparticle consisting of denatured, cross-linked albumin and the agent, the agent selected from a therapeutic agent and a detectable moiety, the nanoparticles selectively binding to and internalized by the activated neutrophils.
2. The method of claim 1 , wherein the neutrophil-mediated inflammatory disease is selected from sepsis, myocardial infarction, acute lung injury, stroke and ischemia-reperfusion injury.
3. The method of claim 1 , wherein delivery of the nanoparticles to activated neutrophils treats a neutrophil-mediated disease or condition.
4. The method of claim 3 , wherein the neutrophil-mediated disease or condition is a neutrophil-mediated inflammatory disease.
5. The method of claim 4 , wherein the therapeutic agent is an anti-inflammatory agent.
6. The method of claim 5 , wherein the anti-inflammatory agent is selected from anti-inflammatory glucocorticoids, NF-kB inhibitors, p38MAP kinase inhibitors, Syk/Zap kinase inhibitors and siRNAs.
7. The method of claim 6 , wherein the anti-inflammatory agent is dexamethasone or piceatannol.
8. The method of claim 1 , wherein the denatured albumin is denatured by desolvation.
9. The method of claim 8 , wherein the albumin is desolvated by treatment with ethanol.
10. The method of claim 1 , wherein the albumin is bovine serum albumin.
11. The method of claim 1 , wherein the therapeutic agent or detectable moiety is loaded within the nanoparticles or covalently conjugated to the albumin.
12. The method of claim 1 , wherein the albumin is cross-linked using glutaraldehyde.
13. The method of claim 1 , wherein the nanoparticles have a mean particle diameter of about 90 to about 110 nm.
14. The method of claim 1 , wherein the detectable moiety is a fluorescent moiety or a chromogenic moiety.
15. A composition comprising nanoparticles, the nanoparticles consisting denatured, cross-linked albumin and an agent selected from a therapeutic agent and a detectable moiety, the nanoparticles being capable of selectively binding to and being internalized by activated neutrophils.
16. The composition of claim 15 , wherein the denatured albumin is denatured by desolvation.
17. The composition of claim 16 , wherein the albumin is desolvated by treatment with ethanol.
18. The composition of claim 15 , wherein the albumin is bovine serum albumin.
19. The composition of claim 15 , wherein the therapeutic agent or detectable moiety is loaded within the nanoparticles or covalently conjugated to the albumin.
20. The composition of claim 15 , wherein the albumin is cross-linked using glutaraldehyde.
21. The composition of claim 15 , wherein the nanoparticles have a mean particle diameter of about 90 to about 110 nm.
22. The composition of claim 15 wherein the agent is a therapeutic agent.
23. The composition of claim 22 , wherein the therapeutic agent is an anti-inflammatory agent.
24. The composition of claim 23 , wherein the anti-inflammatory agent is selected from anti-inflammatory glucocorticoids, NF-kB inhibitors, p38MAP kinase inhibitors, Syk/Zap kinase inhibitors, and siRNA oligonucleotides.
25. The composition of claim 24 , wherein the anti-inflammatory agent is selected from dexamethasone and piceatannol.
26. The composition of claim 15 , wherein the detectable moiety is a fluorescent moiety or a chromogenic moiety.
27. A method of detecting or monitoring neutrophil-mediated diseases comprising contacting neutrophils with the composition of claim 15 and detecting uptake of the detectable moiety by activated neutrophils.