Nanostructure suitable for sequestering cholesterol and other molecules

Patent metadata

Field	Value
Publication number	US-9532948-B2
Application number	US-201213651935-A
Country	US
Kind code	B2
Filing date	Oct 15, 2012
Priority date	Apr 25, 2008
Publication date	Jan 3, 2017
Grant date	Jan 3, 2017

Abstract

Articles, compositions, kits, and methods relating to nanostructures, including those that can sequester molecules such as cholesterol, are provided. Certain embodiments described herein include structures having a core-shell type arrangement; for instance, a nanoparticle core may be surrounded by a shell including a material, such as a lipid bilayer, that can interact with cholesterol and/or other lipids. In some embodiments, the structures, when introduced into a subject, can sequester cholesterol and/or other lipids and remove them from circulation. Accordingly, the structures described herein may be used to diagnose, prevent, treat or manage certain diseases or bodily conditions, especially those associated with abnormal lipid levels.

First claim

What is claimed is:

1. A method for preventing, treating or managing a disease or bodily condition in a subject in need of lower cholesterol levels, comprising:
administering to a subject a therapeutically-effective amount for treating the disease or bodily condition by reducing cholesterol levels in the subject, of a composition comprising a structure comprising a nanostructure core comprising an inorganic material; a shell comprising a lipid bilayer surrounding and attached to the nanostructure core, wherein the shell comprises an apolipoprotein in order to prevent, treat or manage the disease or bodily condition.

2. The method of claim 1 , wherein the lipid bilayer comprises a phospholipid, optionally wherein the lipid bilayer comprises 50-200 phospholipids.

3. The method of claim 1 , wherein the shell comprises 1 to 6 apolipoproteins.

4. The method of claim 1 , wherein the apolipoprotein is apolipoprotein A-I, apolipoprotein A-II, or apolipoprotein E.

5. The method of claim 1 , wherein the structure has a largest cross-sectional dimension of less than or equal to about 50 nm.

6. The method of claim 1 , wherein the nanostructure core has a largest cross-sectional dimension of less than or equal to about 50 nm.

7. The method of claim 1 , wherein at least a portion of the lipid bilayer is covalently bound to the nanostructure core, and/or wherein at least a portion of the lipid bilayer is physisorbed to the nanostructure core.

8. The method of claim 1 , wherein the lipid bilayer is attached to the nanostructure core through a thiol-metal bond.

9. The method of claim 1 , wherein the nanostructure core is formed of a metal.

10. The method of claim 9 , wherein the metal is gold.

11. The method of claim 1 , wherein the core is formed of a semiconductor.

12. The method of claim 1 , wherein the nanostructure core comprises a polymer, and/or wherein the nanostructure core is substantially spherical.

13. The method of claim 1 , wherein the structure further comprises an additional bioactive agent.

14. The method of claim 1 , wherein esterified cholesterol is bound to at least a portion of the shell.

15. The method of claim 1 , wherein the structure comprises a contrast agent.

16. The method of claim 1 , wherein the disease in a subject in need of lower cholesterol levels is selected from the group consisting of a cardiovascular disease, atherosclerosis, hyperlipidemia, a cancer, inflammation, a protein storage disease, a disease of hemostasis, a rheumatic disease and a neurologic disease.

17. The method of claim 1 , wherein the structure comprises a small molecule, bound to the lipid bilayer, that targets a specific cell surface marker.

18. The method of claim 3 , wherein at least a portion of the apolipoprotein is embedded in the shell and/or wherein at least a portion of the apolipoprotein is bound to the nanostructure core, optionally by covalent bonding.

Assignees

• Univ Northwestern

Inventors

• Mirkin Chad A
• Thaxton C Shad
• Giljohann David A
• Daniel Weston

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title