Biomimetic vesicles and uses thereof

Patent metadata

Field	Value
Publication number	US-11446392-B2
Application number	US-201917057415-A
Country	US
Kind code	B2
Filing date	May 23, 2019
Priority date	May 23, 2018
Publication date	Sep 20, 2022
Grant date	Sep 20, 2022

Abstract

The present disclosure relates to unimolecular core-shell nanoparticle, nanoclusters thereof, and platelet biomimetic nanoclusters thereof. The disclosed compositions are useful for treating a subject with a disease or condition, such as a cardiovascular disease. In a further aspect, the cardiovascular disease can be a vascular stenosis or restenosis. Also described herein are methods of making and using the unimolecular core-shell nanoparticle, nanoclusters thereof, and platelet biomimetic nanoclusters thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

First claim

What is claimed is:

1. A biomimetic nanocluster comprising
a cell membrane structure comprising a first cell membrane component; and
a core structure comprising a plurality of unimolecular core-shell nanoparticles, wherein each unimolecular core-shell nanoparticle comprises a functionalized polymer, wherein the functionalized polymer comprises a core-forming segment and a shell-forming segment wherein the functionalized polymer is PAMAM-PVL-COOH, wherein a first pharmaceutical agent is attached to the core-forming polymer, the shell-forming polymer, or both the core-forming polymer and the shell-forming polymer, wherein the first pharmaceutical agent is a bromo and extraterminal (BET) protein inhibitor.

2. The biomimetic nanocluster of claim 1 , wherein the core-forming segment is a dendrimer or a hyperbranched polymer.

3. The biomimetic nanocluster of claim 1 , wherein the core-forming segment is a generation 1, generation 2, generation 3, generation 4, or a generation 5 dendrimer.

4. The biomimetic nanocluster of claim 1 , further comprising a second pharmaceutical agent.

5. The biomimetic nanocluster of claim 4 , wherein the second pharmaceutical agent is a hydrophobic pharmaceutical agent.

6. The biomimetic nanocluster of claim 4 , wherein the second pharmaceutical agent inhibits smooth muscle cell proliferation.

7. The biomimetic nanocluster of claim 1 , wherein the bromo and extraterminal (BET) protein inhibitor is JQ1, RVX208, RO6870810, FT-1101, CPI-0610, ZEN-3694, GSK525762, MK-8628, BMS-986158, INCB054329, RVX297, a derivative thereof, a pharmaceutically acceptable salt thereof, or any combination thereof.

8. The biomimetic nanocluster of claim 1 , wherein the plurality of nanoparticles is homogeneous.

9. The biomimetic nanocluster of claim 1 , wherein the plurality of nanoparticles is heterogeneous.

10. The biomimetic nanocluster of claim 1 , wherein the diameter of the nanoclusters ranges from about 50 nm to about 200 nm.

11. The biomimetic nanocluster of claim 1 , wherein the number of unimolecular core-shell nanoparticles in the plurality of unimolecular core-shell nanoparticles ranges from about 20 to about 1500.

12. The biomimetic nanocluster of claim 1 , wherein the diameter of the core-shell nanoparticle ranges from about 50 nm, to about 200 nm.

13. The biomimetic nanocluster of claim 1 , wherein the biomimetic nanocluster is capable of targeting the vascular endothelium.

14. The biomimetic nanocluster of claim 1 , wherein the first membrane component is derived from a cell-derived membrane vesicle.

15. The biomimetic nanocluster of claim 14 , wherein the cell-derived membrane vesicle is prepared from a mesenchymal stem cell, a peripheral blood mononuclear cell, a platelet, or any combination thereof.

16. A method for treating cardiovascular disease or injury in a subject comprising: administering to the subject the unimolecular core-shell nanoparticle of claim 1 .

Assignees

• Ohio State Innovation Foundation
• Wisconsin Alumni Res Found

Inventors

• Kent K Craig
• Gong Shaoqin
• Guo Lianwang
• Wang Bowen
• Chen Guojun
• Urabe Go

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K47/59

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• A61K9/5153

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61K9/5146

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• A61K31/5517

  condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam · CPC title