Nanoshells on polymers
Nano-constructs comprising nanoshells and methods of using the nano-constructs for treating or ameliorating a medical condition are provided.
1. A nano-construct comprising:
(a) a core material comprising a polymer,
(b) a nanoshell formed on the core material, and
(c) a bioactive agent,
wherein the polymer is a degradable polymer selected from the group consisting of a polyester, poly(ester amide), polyether, polyanhydride, polyorthoester or a non-degradable polymer selected from the group consisting of poly(N-(3-aminopropyl)methacrylamide), a copolymer of N-(3-aminopropyl)methacrylamide, and a combination of these, and
wherein the nanoshell comprises a metal having a thickness from about 5 nm to about 50 nm selected from the group consisting of gold, iron, magnesium, zinc, calcium, tungsten, alloys based on these metals, and combinations thereof.
2. The nano-construct of claim 1 wherein the nanoshell comprises gold.
3. The nano-construct of claim 2 wherein the gold nanoshell has a thickness between about 5 nm and about 25 nm.
4. The nano-construct of claim 1 wherein the core material has a size in the range between about 150 nm to about 2000 nm.
5. The nano-construct of claim 1 wherein the nanoshell on the core material is porous to the bioactive agent.
6. The nano-construct of claim 1 wherein the nanoshell comprises iron, magnesium, zinc, calcium, tungsten, alloys based on these metals, or combinations thereof.
7. The nano-construct of claim 1 wherein the nanoshell comprises an electrically conductive, organic material.
8. The nano-construct of claim 1 wherein the nanoshell comprises graphite or a conductive polymer.
9. The nano-construct of claim 1 wherein the nanoshell comprises poly(L-lactide), polyhydroxyalkanoate, polycaprolactone, or combinations thereof.
10. The nano-construct of claim 1 further comprising a substrate that includes the bioactive agent.
11. The nano-construct of claim 10 wherein the substrate is a small unilamellar vesicle (SUV) encapsulating the bioactive agent.
12. The nano-construct of claim 10 wherein the substrate is a liposome, polymersome, or hybrid vesicle.
13. The nano-construct of the claim 1 wherein the core material further comprises ferromagnetic or magnetic ceramic particles.
14. The nano-construct of claim 1 wherein the core material comprises a peptide, a protein, or a combination of these.
15. The nano-construct of claim 1 further comprising a targeting molecule on the surface of the nano-construct.
16. The nano-construct of claim 15 wherein the targeting molecule is a surface-conjugated ligand for receptors on an inflamed endothelium.
17. The nano-construct of claim 1 in a formulation suitable for systemic delivery or local delivery into a human being.
18. The nano-construct of claim 17 wherein the systemic delivery is injection.
19. The nano-construct of claim 17 wherein the local delivery is delivery by a device comprising a catheter.
20. The nano-construct of claim 1 wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), γ-hirudin clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and combinations of these.
21. A method of forming a nano-construct, comprising:
forming a nanoshell on a core material comprising a polymer, and incorporating at least one bioactive agent with the nanoshell or the core material, wherein the polymer is a degradable polymer or a non-degradable polymer, the non-degradable polymer is selected from the group consisting of poly(N-(3-aminopropyl)methacrylamide), a copolymer of N-(3-aminopropyl)methacrylamide, and a combination of these; and
wherein the nanoshell comprises a metal having a thickness from about 5 nm to about 50 nm selected from the group consisting of gold, iron, magnesium, zinc, calcium, tungsten, alloys based on these metals, and combinations thereof.
22. The method of claim 21 wherein the core material encapsulates at least one bioactive agent.
23. The method of claim 21 wherein the nanoshell is porous.
24. The method of claim 21 further comprising connecting the nano-construct to a substrate.
25. The method of claim 24 wherein the substrate comprises a self-assembled structure.
26. The method of claim 21 wherein the nanoshell comprises gold and has a thickness between about 5 nm and about 25 nm.
27. The method of claim 21 wherein the nanoshell consists essentially of gold and has a thickness between about 5 nm and about 25 nm.
28. The method of claim 21 wherein the core material has a size between about 150 nm and about 2000 nm.
29. The method of claim 21 wherein the core material comprises a peptide, a protein, or a combination of these.
30. The method of claim 21 wherein the nano-construct comprises a targeting molecule on the surface of the nano-construct.
31. The method of claim 29 wherein the targeting molecule is a surface-conjugated ligand for receptors on an inflamed endothelium.
32. The method of claim 21 wherein the nano-construct is in a formulation suitable for systemic delivery or local delivery into a human being.
33. The method of claim 32 wherein the systemic delivery is injection.
34. The method of claim 32 wherein the local delivery is delivery by a device comprising a catheter.
35. The method of claim 21 wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), γ-hirudin, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and combinations of these.
36. A method of treating, preventing, or ameliorating a medical condition, comprising:
delivering to a disease site in the body of a human being in need of treatment the nano-construct of claim 1 ,
wherein the nano-construct releases the bioactive agent.
37. The method of claim 36 wherein the bioactive agent is released by radiating the nano-construct with radiation, and
wherein the nano-construct converts the radiation into heat.
38. The method of claim 37 wherein the radiation uses a near infrared (NIR) electromagnetic radiation transmitted through a catheter-based fiber-optic.
39. The method of claim 37 wherein the radiation is electromagnetic and is applied outside the body of the subject.
40. The method of claim 36 wherein the delivering comprises allowing the nano-construct to extravasate through leaky vasculature in the target tissue.
41. The method of claim 36 wherein the nano-construct comprises targeting molecules on the surface of the nano-construct.
42. The method of claim 41 wherein the targeting molecules comprises surface-conjugated ligands for receptors on an inflamed endothelium.
43. The method of claim 36 wherein the nano-construct comprises a surface-disguising compound on the surface of the nano-construct that increases the circulation time of the nano-construct.
44. The method of claim 43 wherein the surface-disguising compound comprises poly(ethylene glycol).
45. The method of claim 36 wherein medical condition is one or more of atherosclerosis, tumor, a nephrosis, vulnerable plaque, diffuse atherosclerotic disease, diabetic retinopathy, aneurysm, anastomotic hyperplasia, claudication, chronic total occlusion, dysfunctional endothelium, recurring thrombus, or fibrin accumulation.
46. The method of claim 36 wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), γ-hirudin, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and combinations of these.