Polypeptide ligands for targeting cartilage and methods of use thereof

Abstract

Ligands that specifically bind to articular cartilage tissues are disclosed, including uses for targeting therapeutics towards articular cartilage tissue and new materials for articular cartilage. The ligands are effective in vivo to target therapeutic materials to articular cartilage.

1 . A substantially pure polypeptide not found in nature comprising an amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, or a conservative substitution thereof, wherein the polypeptide specifically binds a cartilage tissue. 
     
     
         2 . The polypeptide of  claim 1  wherein the sequence length is between 6 and 1000 residues. 
     
     
         3 . The polypeptide of  claim 1  comprising a therapeutic agent polypeptide. 
     
     
         4 . The polypeptide of  claim 3  wherein the therapeutic agent polypeptide is tissue inhibitor of matrix metalloproteinases-3 (TIMP-3). 
     
     
         5 . The polypeptide of  claim 1  comprising a synthetic backbone linkage. 
     
     
         6 . A substantially pure nucleic acid not found in nature that comprises a nucleic acid sequence that encodes SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:3, or a conservative substitution thereof, wherein a polypeptide encoded by the nucleic acid specifically binds to a cartilage tissue. 
     
     
         7 . The nucleic acid of  claim 6  wherein the polypeptide that is encoded comprises a therapeutic agent polypeptide. 
     
     
         8 . A vector comprising the nucleic acid of  claim 6 . 
     
     
         9 . A method of treating cartilage of a mammal comprising administering to the mammal a pharmaceutically acceptable composition that comprises the polypeptide of  claim 1 , wherein the polypeptide targets the therapeutic agent to the cartilage tissue by specifically binding cartilage tissue of the mammal. 
     
     
         10 . A delivery system for delivering a therapeutic agent comprising: a substantially purified preparation that comprises a pharmaceutically acceptable excipient, a therapeutic agent, and a polypeptide ligand not found in nature comprising an amino acid sequence in the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, and conservative substitutions thereof, wherein the polypeptide ligand specifically binds a cartilage tissue for targeted delivery of the therapeutic agent to cartilage tissues. 
     
     
         11 . The delivery system of  claim 10  wherein the therapeutic agent comprises a drug, a visualization agent, or a therapeutic polypeptide. 
     
     
         12 . The delivery system of  claim 10  comprising a fusion polypeptide that comprises the polypeptide ligand and the therapeutic agent. 
     
     
         13 . The delivery system of  claim 10  comprising a molecule that comprises covalent bonds to the polypeptide ligand and the therapeutic agent. 
     
     
         14 . The delivery system of  claim 10  wherein the polypeptide ligand is covalently bonded to a biocompatible polymer that is associated with the therapeutic agent. 
     
     
         15 . The delivery system of  claim 14  wherein the biocompatible polymer is free of amino acids. 
     
     
         16 . The delivery system of  claim 10  comprising a collection of nanoparticles having an average diameter of between about 10 nm and about 200 nm, wherein the nanoparticles comprise the therapeutic agent and the polypeptide ligand. 
     
     
         17 . A method of treating cartilage of a mammal comprising administering to the mammal a pharmaceutically acceptable composition that comprises the delivery system of  claim 13 , wherein the polypeptide targets the therapeutic agent to the cartilage tissue by specifically binding cartilage tissue of the mammal. 
     
     
         18 . The method of  claim 17  wherein the composition is administered intra-articularly.