Polymer nanoparticles coated by magnetic metal oxide and uses thereof

Abstract

The invention provides nanoparticles consisting of a polymer which is a metal chelating agent coated with a magnetic metal oxide, wherein at least one active agent is covalently bound to the polymer, said nanoparticles may optionally further comprise at least one active agent physically or covalently bound to the outer surface of the magnetic metal oxide. Pharmaceutical compositions comprising these nanoparticles may be used, inter alia, for detection and treatment of tumors and inflammations.

1 .- 64 . (canceled) 
     
     
         65 . A nanoparticle comprising a metal chelating polymer, a magnetic metal oxide, and at least one active agent covalently bound to said polymer. 
     
     
         66 . The nanoparticle of  claim 65 , wherein said metal chelating polymer is gelatin, polymethylenimine, chitosan or polylysine. 
     
     
         67 . The nanoparticle of  claim 65 , wherein said magnetic metal oxide is an iron oxide or a ferrite derived from an iron oxide. 
     
     
         68 . The nanoparticle of  claim 67 , wherein said iron oxide is magnetite, maghemite or a mixture thereof. 
     
     
         69 . The nanoparticle of  claim 65 , wherein said at least one active agent is a fluorescent dye, a contrast agent, a peptide or peptidomimetic, a polypeptide, an antifolate drug, an antibiotic, an anti-inflammatory agent, an anthracycline chemotherapeutic agent, or any combination thereof. 
     
     
         70 . The nanoparticle of  claim 69 , wherein said fluorescent dye is rhodamine or fluorescein. 
     
     
         71 . The nanoparticle of  claim 69 , wherein said peptide or peptidomimetic is a cyclic RGD (cRGD) or an acyclic RGD. 
     
     
         72 . The nanoparticle of  claim 69 , wherein said polypeptide is TNF-related apoptosis-inducing ligand (TRAIL) or interleukin-12 (IL 12). 
     
     
         73 . The nanoparticle of  claim 69 , wherein said antifolate drug is methotrexate. 
     
     
         74 . The nanoparticle of  claim 69 , wherein said anthracycline chemotherapeutic agent is doxorubicine. 
     
     
         75 . The nanoparticle of  claim 65 , further comprising at least one additional active agent bound to an outer surface of said nanoparticle. 
     
     
         76 . The nanoparticle of  claim 75 , wherein said at least one additional active agent is covalently bound to the outer surface of the nanoparticle via a linker. 
     
     
         77 . The nanoparticle of  claim 76 , wherein said linker is derived from a polysaccharide, protein, peptide, polyamine, polyethyleneglycol, acryloyl chloride, divinyl sulfone (DVS), dicarbonyl imidazole, ethylene glycolbis(sulfosuccinimidylsuccinate), m-maleimidobenzoic acid N-hydroxysulfosuccinimide ester or any combination thereof 
     
     
         78 . The nanoparticle of  claim 75 , wherein said at least one additional active agent bound to the outer surface of the nanoparticle is a fluorescent dye, a contrast agent, a peptide or a peptidomimetic, a polypeptide, an antifolate drug, an antibiotic, an anti-inflammatory agent, an anthracycline chemotherapeutic agent or any combination thereof 
     
     
         79 . The nanoparticle of  claim 78 , wherein said peptide or peptidomimetic is a cyclic RGD (cRGD) or an acyclic RGD. 
     
     
         80 . The nanoparticle of  claim 78 , wherein said polypeptide is a cytokine, an enzyme, an antibody or a hormone. 
     
     
         81 . The nanoparticle of  claim 80 , wherein said antibody is Bevacizumab (trade name: avastin) or Infliximab (trade name: remicade). 
     
     
         82 . The nanoparticle of  claim 78 , wherein said polypeptide is TNF-related apoptosis-inducing ligand (TRAIL) or interleukin-12 (IL12). 
     
     
         83 . A pharmaceutical composition comprising a nanoparticle of  claim 65  and a pharmaceutically acceptable carrier. 
     
     
         84 . A method for detecting a tumor in an individual comprising administering to said individual a nanoparticle according to  claim 65 , wherein TRAIL, cRGD peptide, IL-12, doxorubicin, methotrexate or any combination thereof is bound to the outer surface of the nanoparticle, and a contrast agent or a fluorescent dye is covalently bound to said polymer. 
     
     
         85 . A method for inducing apoptosis, autophagy, or both in a cancer cell, comprising the step of contacting said cell with a nanoparticle of  claim 75 , wherein said at least one active agent is TRAIL, cRGD peptide, IL-12, doxorubicin, methotrexate, bevacizumab or any combination thereof, and wherein said cancer cell is a glioma cell, a cancer stem cell, a cervical carcinoma cell, a bladder carcinoma cell, a breast cancer cell, an ovarian cancer cell, or a lung cancer cell. 
     
     
         86 . The method according to  claim 85 , wherein said inducing apoptosis, autophagy, or both in a cancer cell is treating a patient afflicted with glioma, cervical carcinoma, bladder carcinoma, breast cancer, ovarian cancer or a lung cancer. 
     
     
         87 . The method of  claim 85 , further comprising the step of contacting said cell with a proteasome inhibitor. 
     
     
         88 . The method according to  claim 85 , further comprising the step of Gamma irradiating said cell. 
     
     
         89 . A method for employing X-ray imaging or magnetic resonance imaging (MRI) in a subject, comprising administering to said subject a nanoparticle according to  claim 65 , wherein said active agent is a contrast agent. 
     
     
         90 . A method for detecting inflammation in a subject comprising administering to said subject a nanoparticle according to  claim 65 , wherein said magnetic metal oxide is iron oxide, and said at least one active agent is a fluorescent dye or a contrast agent. 
     
     
         91 . A method for treating inflammation in a subject comprising administering to said subject a nanoparticle according to  claim 65 , wherein said magnetic metal oxide is iron oxide, and said at least one active agent is an anti-inflammatory agent.