Cartilage-homing peptides

Abstract

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.

What is claimed: 
     
         1 - 118 . (canceled) 
     
     
         119 . A method of delivering a composition to a cartilage of a subject, the method comprising administering the composition to the subject, wherein the composition comprises a peptide having:
 (a) at least 90% sequence identity to SEQ ID NO: 327 or SEQ ID NO: 240,   (b) at least 90% sequence identity to SEQ ID NO: 325 or SEQ ID NO: 238, or   (c) at least 90% sequence identity to SEQ ID NO: 416 or SEQ ID NO: 421;   wherein the peptide homes, targets, or migrates to the cartilage of the subject following administration.   
     
     
         120 . The method of  claim 119 , wherein the composition further comprises an active agent linked to the peptide. 
     
     
         121 . The method of  claim 120 , wherein the active agent comprises a therapeutic agent, a detectable agent, or a combination thereof. 
     
     
         122 . The method of  claim 121 , wherein the therapeutic agent comprises a therapeutic small molecule. 
     
     
         123 . The method of  claim 121 , wherein the therapeutic agent comprises an antibiotic, an anti-viral agent, an anti-fungal agent, an anti-inflammatory agent, a protease inhibitor, an immune modulator, an anti-cytokine agent, a tyrosine kinase inhibitor, a growth factor, a cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitor, a B-cell lymphoma 2 (BCL-2) family inhibitor, a tumor necrosis factor alpha (TNF-α) modulator, a tumor necrosis factor receptor (TNFR) family modulator, or any combination thereof. 
     
     
         124 . The method of  claim 123 , wherein the anti-inflammatory agent comprises a steroid or a nonsteroidal anti-inflammatory drug (NSAID). 
     
     
         125 . The method of  claim 124 , wherein the steroid is a corticosteroid or a glucocorticoid. 
     
     
         126 . The method of  claim 124 , wherein the steroid is triamcinolone acetonide, dexamethasone, budesonide, triamcinolone, cortisone, prednisone, prednisolone, triamcinolone hexacetonide, or methylprednisolone. 
     
     
         127 . The method of  claim 124 , wherein the NSAID is ibuprofen, naproxen, ketorolac, indomethacin, etodolac, tolemetin, celecoxib, aceclofenac, nabumetone, sulindac, or diclofenac. 
     
     
         128 . The method of  claim 123 , wherein the protease inhibitor is a matrix metalloprotease 13 (MMP13) inhibitor. 
     
     
         129 . The method of  claim 121 , wherein the therapeutic agent comprises imatinib mesylate or methotrexate. 
     
     
         130 . The method of  claim 121 , wherein the therapeutic agent comprises a therapeutic peptide. 
     
     
         131 . The method of  claim 130 , wherein the therapeutic peptide is a cytokine, an enzyme, a growth factor, a chemokine, a neurotransmitter, an Fc region, or any combination thereof. 
     
     
         132 . The method of  claim 121 , wherein the therapeutic agent comprises an antibody or an antibody fragment. 
     
     
         133 . The method of  claim 121 , 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. 
     
     
         134 . The method of  claim 119 , wherein the peptide comprises 4 or more cysteine residues and a plurality of disulfide bridges formed between cysteine residues. 
     
     
         135 . The method of  claim 119 , wherein the peptide comprises a sequence of SEQ ID NO: 327, SEQ ID NO: 325, SEQ ID NO: 240, SEQ ID NO: 238, SEQ ID NO: 416, or SEQ ID NO: 421. 
     
     
         136 . The method of  claim 119 , comprising administering the composition by inhalation, intranasally, orally, topically, intravenously, subcutaneously, intra-articularly, intramuscularly, intraperitoneally, or a combination thereof. 
     
     
         137 . The method of  claim 119 , further comprising treating a condition in the subject. 
     
     
         138 . The method of  claim 137 , wherein the condition is associated with the cartilage. 
     
     
         139 . The method of  claim 137 , wherein the condition is a type of arthritis or lupus. 
     
     
         140 . The method of  claim 137 , wherein the condition is rheumatoid arthritis, osteoarthritis, gout, pseudogout, ankylosing spondylitis, or psoriatic arthritis. 
     
     
         141 . The method of  claim 119 , further comprising detecting a condition in the cartilage. 
     
     
         142 . The method of  claim 141 , wherein the condition comprises a lesion, a degradation, a growth disturbance, a tear, an infection, an inflammation, or an injury. 
     
     
         143 . The method of  claim 142 , wherein the lesion comprises a tumor or a metastasis. 
     
     
         144 . The method of  claim 142 , further comprising surgically removing the lesion.