Self-assembled brush block copolymer-nanoparticles for drug delivery
The invention provides amphiphilic liquid crystalline brush block copolymers that can readily self-assemble to nanoparticles in aqueous solutions and also allow for encapsulation of hydrophobic pharmaceutically active molecules.
1. A block copolymer comprising:
a first block, which is of formula:
and a second block, which is of formula:
wherein
m and n are independently an integer about 3 to about 500;
A is independently selected from polynorbonene, polycyclopentene, polycyclooctene, polyacrylate, polymethacrylate, and a polysiloxane;
R 1 is a steroid moiety optionally comprising a linker; and
R 2 is a polyalkylene oxide moiety.
2. The block copolymer of claim 1 , wherein the steroid moiety comprises cholesterol, cholic acid, deoxycholic acid, or taurocholic acid.
3. The block copolymer of claim 2 , wherein the steroid moiety comprises cholesterol.
4. The block copolymer of claim 1 , wherein the linker at R 1 is
a polylactone, or an oligomer of siloxane.
5. The block copolymer of claim 1 , wherein the polyalkylene oxide moiety comprises polyethylene oxide or polyethylene oxide thiolate.
6. The block copolymer of claim 1 , wherein each A is independently polynorbonene or polyacrylate.
7. The block copolymer of claim 1 , comprising the structure:
wherein
x is an integer between about 3 and about 100;
m is an integer between about 5 and about 200; and
n is an integer between about 5 and about 100.
8. The block copolymer of claim 7 , wherein x is between about 5 and about 50.
9. The block copolymer of claim 7 , wherein m is between about 10 and about 100.
10. The block copolymer of claim 7 , wherein n is between about 15 and about 85.
11. The block copolymer of claim 1 , wherein the molecular weight of the block copolymer is about 10,000 to about 1,000,000 Da.
12. The block copolymer of claim 1 , wherein the block copolymer is in a core/shell nanoparticle form.
13. A nanoparticle comprising a block copolymer nanoparticle in a core/shell form and a hydrophobic pharmaceutically active molecule, wherein the block polymer comprises:
a first block, which is of formula:
and a second block, which is of formula:
wherein
m and n are independently an integer about 3 to about 500;
A is independently selected from polynorbonene, polycyclopentene, polycyclooctene, polyacrylate, polymethacrylate, and a polysiloxane;
R 1 is a steroid moiety optionally comprising a linker; and
R 2 is a polyalkylene oxide moiety.
14. The nanoparticle of claim 13 , wherein the hydrophobic molecule is doxorubicin, daunorubicin, vincristin, paclitaxel, docetaxel, cisplatin, camptothecin, irinotecan, 5-fluorouracil, methotrexate, or dexamethasone.
15. The nanoparticle of claim 13 , further comprising one or more metal nanoparticles.
16. The nanoparticle of claim 15 , wherein the metal nanoparticle is a gold nanoparticle, a magnetic nanoparticle, or a quantum dot.
17. The nanoparticle of claim 13 , wherein the nanoparticle is between about 5 and about 500 nm in diameter.
18. A method of delivering a pharmaceutically active molecule, comprising administering to a subject the nanoparticle according to claim 13 .
19. A process for preparing a nanoparticle of claim 13 , comprising
(a) dissolving a block copolymer in an organic solvent to obtain a copolymer solution,
wherein the block polymer comprises
a first block, which is of formula:
and a second block, which is of formula:
wherein
m and n are independently an integer about 3 to about 500;
A is independently selected from polynorbonene, polycyclopentene, polycyclooctene, polyacrylate, polymethacrylate, and a polysiloxane;
R 1 is a steroid moiety optionally comprising a linker; and
R 2 is a polyalkylene oxide moiety; and
(b) mixing the copolymer solution in an aqueous solution to form a nanoparticle.
20. The nanoparticle of claim 13 , wherein the steroid moiety comprises cholesterol, cholic acid, deoxycholic acid, or taurocholic acid.
21. The nanoparticle of claim 13 , wherein the linker at R 1 is
a polylactone, or an oligomer of siloxane.
22. The nanoparticle of claim 13 , wherein the polyalkylene oxide moiety comprises polyethylene oxide or polyethylene oxide thiolate.
23. The nanoparticle of claim 13 , wherein each A is independently polynorbonene or polyacrylate.
24. The nanoparticle of claim 13 , comprising the structure:
wherein
x is an integer between about 3 and about 100;
m is an integer between about 5 and about 200; and
n is an integer between about 5 and about 100.
25. The nanoparticle of claim 13 , wherein x is between about 5 and about 50; m is between about 10 and about 100; and n is between about 15 and about 85.
26. The nanoparticle of claim 13 , wherein the molecular weight of the block copolymer is about 10,000 to about 1,000,000 Da.