Targeted nanoparticles
Described herein are carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a nitroboronic boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing the nitroboronic acid to an environment external to the nanoparticle. Targeted versions of the described nanoparticles are also described, as are related compositions, methods and systems.
1. A polymer conjugate comprising a polymer containing a polyol and a polymer containing a nitrophenylboronic acid,
wherein the polymer containing the nitrophenylboronic acid has a linkage cleavable under reducing conditions and is conjugated to the polymer containing the polyol with a reversible borate ester linkage, and
wherein the polymer containing the polyol is derived from the coupling of a compound of Formula A with a compound of Formula B;
wherein
the compound of Formula A is:
in which
the spacer is independently selected from any organic group;
the amino acid is selected from any organic group bearing a free amine and a free carboxylic acid group;
n is 1-20; and
Z 1 is independently selected from —NH 2 , —OH, —SH, and COOH; and
the compound of Formula B is:
in which
q is a number from 1 to 20;
p is a number from 20 to 200; and
L is a leaving group.
2. A polymer conjugate comprising a polymer containing a polyol and a polymer containing a nitrophenylboronic acid,
wherein the polymer containing the nitrophenylboronic acid has a linkage cleavable under reducing conditions and is conjugated to the polymer containing the polyol with a reversible borate ester linkage, and
wherein the polymer containing the polyol is derived from the coupling of a compound of Formula A with a compound of Formula B;
wherein
the compound of Formula A is:
wherein n is a number from 1 to 20; and
the compound of Formula B is:
in which
q is a number from 1 to 20;
p is a number from 20 to 200; and
L is a leaving group.
3. The polymer conjugate of claim 1 , wherein compound of Formula B is:
4. The polymer conjugate of claim 2 , wherein the polymer containing the polyol comprises units of the formula:
5. The polymer conjugate of claim 3 , wherein n is 1 and q is 1.
6. The polymer conjugate of claim 1 , wherein compound of Formula B is:
7. The polymer conjugate of claim 2 , wherein the polymer containing the polyol comprises units of the formula:
8. The polymer conjugate of claim 7 , wherein n is 1 and p is 1.
9. The polymer conjugate of claim 1 , wherein the polymer containing the nitrophenylboronic acid that has a linkage cleavable under reducing conditions comprises at least one terminal nitrophenylboronic acid group and has the general formula:
wherein
R 3 and R 4 are independently (CH 2 CH 2 O) t , where t is from 2 to 2000;
X 1 is —S—S—;
Y 1 is a nitrophenyl group;
r=1; a=0; and b=1; and
wherein Functional group 1 and Functional group 2 independently comprise a —B(OH)2, —OCH 3 , —COOH, —NH 2 , or —OH group.
10. The polymer conjugate of claim 2 , wherein the polymer containing the nitrophenylboronic acid that has a linkage cleavable under reducing conditions comprises at least one terminal nitrophenylboronic acid group and has the general formula:
wherein
R 3 and R 4 are independently (CH 2 CH 2 O) t , where t is from 2 to 2000;
X 1 is —S—S—;
Y 1 is a nitrophenyl group;
r=1; a=0; and b=1; and
wherein Functional group 1 and Functional group 2 independently comprise a —B(OH) 2 , —OCH 3 , —COOH, —NH 2 , or —OH group.
11. The polymer conjugate of claim 9 , wherein Functional group 2 comprises a —B(OH) 2 , —OCH 3 , —OH, or —COOH group.
12. The polymer conjugate of claim 9 , wherein the polymer containing the nitrophenylboronic acid that has a linkage cleavable under reducing conditions is:
wherein t is a number from 200 to 300.
13. The polymer conjugate of claim 10 , wherein the polymer containing the nitrophenylboronic acid that has a linkage cleavable under reducing conditions is:
wherein t is a number from 2 to 2000.
14. The polymer conjugate of claim 9 , in which the polymer conjugate is in the form of a nanoparticle.
15. The polymer conjugate of claim 10 , in which the polymer conjugate is in the form of a nanoparticle.
16. The nanoparticle of claim 14 , further comprising a therapeutic agent.
17. The nanoparticle of claim 15 , further comprising a therapeutic agent.
18. The nanoparticle of claim 15 , further comprising a small molecule chemotherapeutic agent or a polynucleotide or both a small molecule chemotherapeutic agent and a polynucleotide.
19. The nanoparticle of claim 18 , wherein the polynucleotide is interfering RNA.
20. The nanoparticle of claim 18 , wherein the small molecule chemotherapeutic is camptothecin, an epothilone, a taxane or a combination thereof.
21. The nanoparticle of claim 16 , wherein the nanoparticle is further conjugated to at least one targeting ligand.
22. The nanoparticle of claim 17 , wherein the nanoparticle further conjugated to at least one targeting ligand.
23. The nanoparticle of claim 16 , where the nanoparticle is further conjugated to only a single targeting ligand.
24. The nanoparticle of claim 17 , wherein the nanoparticle is further conjugated to only a single targeting ligand.
25. The nanoparticle of claim 21 , wherein at least one of the targeting ligand is an antibody, transferrin, a ligand for a cellular receptor, a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.
26. A method to deliver a therapeutic agent to a target, the method comprising contacting the target with the nanoparticle of claim 22 .
27. The method of claim 26 , wherein the target is a cancer cell within the body of a mammal.
28. The nanoparticle of claim 16 , wherein the therapeutic agent is conjugated to the polymer containing the polyol.
29. The nanoparticle of claim 17 , wherein the therapeutic agent is conjugated to the polymer containing the polyol.
30. The nanoparticle of claim 16 , wherein the therapeutic agent is conjugated to the polymer containing the nitrophenylboronic acid.
31. The nanoparticle of claim 17 , wherein the therapeutic agent is conjugated to the polymer containing the nitrophenylboronic acid.
32. The nanoparticle of claim 22 , wherein at least one of the targeting ligand is an antibody, transferrin, a ligand for a cellular receptor, a cellular receptor protein, an aptamer, or a fragment of an antibody, transferrin, a ligand for a cellular receptor, or a cellular receptor protein.
33. The nanoparticle of claim 21 , wherein at least one of the targeting ligand is Herceptin.
34. The nanoparticle of claim 22 , wherein at least one of the targeting ligand is Herceptin.