Cartilage-homing peptides
Peptides that home, target, migrate to, are directed to, are retained by, or accumulate in and/or binds to the cartilage of a subject are disclosed. Pharmaceutical compositions and uses for peptides or peptide-active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of a drug to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver peptide or peptide-active agent complexes to target regions, tissues, structures or cells targeted by the peptide.
1. A composition comprising a knotted peptide, the knotted peptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 327.
2. The composition of claim 1 , wherein the knotted peptide comprises:
(a) 4 or more cysteine residues; or
(b) a plurality of disulfide bridges formed between cysteine residues.
3. The composition of claim 1 , wherein the knotted peptide homes, targets, migrates to, accumulates in, binds to, is retained by, or is directed to a cartilage.
4. The composition of claim 1 , wherein the knotted peptide has a positive charge at physiological pH.
5. The composition of claim 1 , wherein the knotted peptide has a charge of at least 2 at physiological pH.
6. The composition of claim 1 , wherein the knotted peptide has an isoelectric point (pI) of greater than 7.4.
7. The composition of claim 1 , wherein the knotted peptide is linked to an active agent.
8. The composition of claim 7 , wherein the active agent comprises a therapeutic small molecule.
9. The composition of claim 8 , wherein the therapeutic small molecule comprises a steroid.
10. The composition of claim 9 , wherein the steroid comprises a corticosteroid.
11. The composition of claim 10 , wherein the corticosteroid comprises a glucocorticoid.
12. The composition of claim 11 , wherein the glucocorticoid is dexamethasone or budesonide.
13. The composition of claim 10 , wherein the corticosteroid comprises triamcinolone.
14. The composition of claim 13 , wherein the triamcinolone comprises triamcinolone acetonide.
15. The composition of claim 8 , wherein the therapeutic small molecule comprises a protease inhibitor.
16. The composition of claim 15 , wherein the protease inhibitor comprises a matrix metalloprotease 13 (MMP13) inhibitor.
17. The composition of claim 8 , wherein the therapeutic small molecule comprises an antibiotic, an anti-viral agent, an anti-fungal agent, an anti-inflammatory agent, or any combination thereof.
18. The composition of claim 17 , wherein the anti-inflammatory agent comprises a nonsteroidal anti-inflammatory drug (NSAID).
19. The composition of claim 7 , wherein the active agent comprises a peptide.
20. The composition of claim 19 , wherein the peptide comprises a cytokine, an enzyme, a growth factor, a chemokine, a neurotransmitter, an Fc region, or any combination thereof.
21. The composition of claim 7 , wherein the active agent comprises an immune modulator.
22. The composition of claim 7 , wherein the active agent comprises an antibody or an antibody fragment.
23. The composition of claim 7 , wherein the active agent comprises an anti-cytokine agent.
24. The composition of claim 7 , wherein the active agent comprises a therapeutic agent, a detectable agent, or a combination thereof.
25. The composition of claim 24 , wherein the detectable agent comprises: a fluorophore, a metal, a metal chelate, an X-ray contrast agent, a PET agent, a radioisotope, a photosensitizer, a radiosensitizer, a radionuclide chelator, or any combination thereof.
26. A pharmaceutical composition comprising the composition of claim 1 , and a pharmaceutically acceptable carrier.
27. The pharmaceutical composition of claim 26 , wherein the pharmaceutical composition is formulated for inhalation, intranasal administration, oral administration, intravenous administration, subcutaneous administration, intra-articular administration, intramuscular administration, intraperitoneal administration, administration locally into an affected area, administration into a joint, or any combination thereof.