Biomimetic vesicles and uses thereof
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.
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 .