Carrier nanoparticles and related compositions, methods and systems
Carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing a boronic acid to an environment external to the nanoparticle and related compositions, methods and systems.
1. A method of delivering a therapeutic agent to a human patient, to treat a functional disorder in a human patient's body, the method comprising administering to the human patient a plurality of nanoparticles having a targeting ligand and a therapeutic agent effective for treating the functional disorder, wherein
each nanoparticle comprises a polymer containing a polyol and a polymer containing a phenylboronic acid,
wherein the polymer containing the phenylboronic acid is conjugated to the polymer containing the polyol with a reversible borate ester linkage;
wherein the nanoparticle is configured to present the polymer containing a phenylboronic acid to an environment external to the nanoparticle;
wherein the polymer containing a polyol comprises one or more of at least one of the following structural units of Formula (I), (II), or (II):
wherein A is independently derived from
and
wherein B is derived from:
in which
q is 1-20;
p is 20-200; and
L is a leaving group; and
wherein the polymer containing a phenylboronic acid comprises at least one terminal phenylboronic 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 —NH—C(═O)—, —S—S—, —C(═O)—NH—, —O—C(═O)— or —C(═O)—O—,
Y 1 is a phenyl group,
wherein r=1, a=0 and b=1, and
wherein Functional group 1 and Functional group 2 are the same or different and independently comprise —B(OH) 2 , —OCH 3 , —(X 1 )—(Y 1 )—B(OH) 2 , —COOH, —NH 2 , or —OH.
2. The nanoparticle of claim 1 , wherein the structural unit of formula (I) is:
3. The nanoparticle of claim 1 , wherein the structural unit of formula (II) is:
4. The nanoparticle of claim 1 , wherein the structural unit of formula (III) is:
in which
n is 1-20.
5. The nanoparticle of claim 1 , wherein the polymer containing the polyol has a repeating unit of:
6. The nanoparticle of claim 2 , wherein functional group 1 and functional group 2 are the same or different and are independently selected from —B(OH) 2 , —OCH 3 , —OH.
7. The nanoparticle of claim 2 , wherein the polymer containing a phenylboronic acid is:
wherein t is a number from 200 to 300.
8. The method of claim 1 , wherein the functional disorder is a mental disorder.
9. The method of claim 1 , wherein the functional disorder is a physical disorder.
10. The method of claim 1 , wherein the therapeutic agent is a chemotherapeutic agent.
11. The method of claim 10 , wherein the chemotherapeutic agent is an epothilone, a camptothecin-based drug, taxol, or a nucleic acid, or a combination thereof.
12. The method of claim 10 , wherein the chemotherapeutic is camptothecin, an epothilone, a taxane or a combination thereof.
13. The method of claim 11 , wherein the nucleic acid is a plasmid, siRNA, shRNA, miRNA, antisense oligonucleotide, aptamer, or a combination thereof.
14. The method of claim 1 , wherein the targeting ligand is a vitamin, a protein, a monosaccharide, a peptide, a peptide aptamer, an oligopeptide, a polypeptide or fragment thereof, a polysaccharide, a polynucleotide, an antibody, or an antibody fragment.
15. The method of claim 1 , wherein the targeting ligand is transferrin, folic acid, or galactose.
16. The method of claim 14 , wherein the polynucleotide is interfering RNA.
17. The method of claim 1 , wherein the targeting ligand is a ligand for a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein.
18. The method of claim 1 , wherein the functional disorder is a mental or physical disorder, and the targeting ligand is a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein.