Biospecific agents for bone

Abstract

A bone biospecific agent comprises a contrast material core, which is visible using Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The contrast material core is surrounded by a polymeric shell, which is functionalised with a bone-targeting peptide. In use, the peptide targets the biospecific agent to bone. The bone biospecific agent can be used in diagnostic imaging techniques, such as MRI and CT, and in imaging bone remodelling activities, detecting and treating pathological bone conditions and/or bone repair processes. The invention extends to the diagnosis and/or treatment of bone disease and bone pathologies using the biospecific agents.

1 - 35 . (canceled) 
     
     
         36 . A bone biospecific agent comprising a contrast material core, which is visible using Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), the contrast material core being optionally surrounded by a polymeric shell, wherein the core or polymeric shell is functionalised with a bone-targeting peptide, wherein the peptide, in use, targets the biospecific agent to bone, and wherein the peptide mimics proteins participating in the inhibition of osteoclast-osteoclast and/or osteoclast-osteoblast interactions, or recognises the mineral phase of bone. 
     
     
         37 . A biospecific agent according to  claim 36 , wherein the contrast material core comprises a magnetic material, and is an MRI contrast material. 
     
     
         38 . A biospecific agent according to  claim 36 , wherein the contrast material core comprises iron, nickel, cobalt or dysprosium or an oxide or alloy, which contains one or more of these elements. 
     
     
         39 . A biospecific agent according to  claim 36 , wherein the contrast material comprises magnetite (Fe 3 O 4 ). 
     
     
         40 . A biospecific agent according to  claim 36 , wherein the contrast material core comprises a non-magnetic material, and is both an MRI and a CT contrast material. 
     
     
         41 . A biospecific agent according to  claim 36 , wherein the contrast material core comprises gadolinium, gold, iodine or boro-sulphate. 
     
     
         42 . A biospecific agent according to  claim 36 , wherein the polymeric shell comprises a biocompatible natural or synthetic polymer including chitosan, collagen, gelatine, hyaluronic acid, poly(ethylene glycol) poly(lactic acid), poly(glycolic acid), poly(epsilon-caprolactone) or poly(acrylic acid). 
     
     
         43 . A biospecific agent according to  claim 36 , wherein the polymeric shell is derivatised with succinic anhydride. 
     
     
         44 . A biospecific agent according to  claim 36 , wherein the polymeric shell is functionalised with one, two or more species of bone-targeting peptide, which target the biospecific agent to bone. 
     
     
         45 . A biospecific agent according to  claim 36 , wherein the bone-targeting peptide targets the biospecific agent to: (i) a cell present exclusively in bone and selected from a group consisting of an osteoblast, osteocyte, osteoclast, bone cell progenitor, osteoclast progenitor and a bone lining cell; or (ii) to the bone mineral phase or hydroxyapatite. 
     
     
         46 . A biospecific agent according to  claim 36 , wherein the bone-targeting peptide comprises an amino acid sequence that mimics OPG by binding RANK, such that RANKL-induced osteoclast differentiation and activity is reduced or prevented. 
     
     
         47 . A biospecific agent according to  claim 36 , wherein the bone-targeting peptide comprises a peptide selected from SEQ ID No.1-15. 
     
     
         48 . A biospecific agent according to  claim 36 , wherein the bone-targeting peptide is attached to the polymeric shell of the bone biospecific agent by covalent bonding or by carbodiimide chemistry. 
     
     
         49 . A biospecific agent according to  claim 36 , wherein the biospecific agent comprises a bioactive compound, which is delivered to the bone due to the presence of the bone-targeting peptide. 
     
     
         50 . A biospecific agent according to  claim 49 , wherein the bioactive compound is selected from a group of molecules consisting of: a dye, electrochemical mediator, protein, peptide, chemical compound, a drug, genetic material, an oligonucleotide, DNA, RNA, small molecule, antibody, and an enzyme. 
     
     
         51 . A biospecific agent according to  claim 36 , wherein the mean diameter of the biospecific agent is 100-450 nm. 
     
     
         52 . A biolabel comprising the bone biospecific agent according to  claim 36 . 
     
     
         53 . An MRI or CT imaging method comprising the use of the bone biospecific agent according to  claim 36 . 
     
     
         54 . A method of treating, ameliorating or preventing bone disease, the method comprising administering, to a subject in need of such treatment, a therapeutically effective amount of a bone biospecific agent according to  claim 36 , optionally wherein the bone disease is selected from a group consisting of: bone resorption, treatment of bone tumour, Paget's disease, osteoarthritis, osteoporosis, osteosarcoma, osteopenia and bone metastases, including osteolytic and osteoblastic phenotypes. 
     
     
         55 . A pharmaceutical composition comprising the bone biospecific agent according to  claim 36 , and a pharmaceutically acceptable vehicle.