US2016051708A1PendingUtilityA1

Metal Oxide Nanoparticle-Based Magnetic Resonance Imaging Contrast Agent with a Central Cavity

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Assignee: INTRON BIOTECHNOLOGY INCPriority: Apr 5, 2013Filed: Apr 5, 2013Published: Feb 25, 2016
Est. expiryApr 5, 2033(~6.7 yrs left)· nominal 20-yr term from priority
Inventors:Kwang Yeol LeeMin Sik KimTaek Hoon KimNgoc Phan Vu
H01M 4/8652H01M 4/9016H01M 4/52B01J 20/28016B01J 20/06B01J 35/0013B01J 23/8892A61K 49/1818A61K 49/186H01M 4/50H01M 4/364A61K 49/1875A61K 49/06A61K 39/395A61K 47/30A61K 9/16Y02E60/50Y02E60/10
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Claims

Abstract

The present invention relates to a magnetic resonance imaging (MRI) contrast agent, particularly an MRI contrast agent derived from nanoparticle that is porous first metal-doped second metal oxide nanoparticle with a central cavity, and a method for producing the same. The MRI contrast agent made in accordance with the present invention can be used not only as a drug-delivery agent for therapy but also as an MRI contrast agent for diagnosis.

Claims

exact text as granted — not AI-modified
1 . A nanoparticle-based MRI contrast agent comprising a porous metal oxide nanoparticle with a central cavity and being used not only as a drug-delivery agent but also as an MRI contrast agent. 
     
     
         2 . The nanoparticle-based MRI contrast agent according to  claim 1 , wherein the porous metal oxide is paramagnetic or superparamagnetic metal oxides. 
     
     
         3 . The nanoparticle-based MRI contrast agent according to  claim 2 , wherein the paramagnetic or superparamagnetic metal oxides are at least one selected from the group consisting of iron oxide, chromium oxide, gadolinium oxide, cobalt oxide and nickel oxide. 
     
     
         4 . The nanoparticle-based MRI contrast agent according to  claim 1 , wherein the central cavity has at least one shape selected from the group consisting of octahedral, cross-shaped, urchin-shaped, and cubic. 
     
     
         5 . The nanoparticle-based MRI contrast agent according to  claim 2 , wherein the paramagnetic or superparamagnetic metal oxides comprise the doped metal ions different from the metal of the paramagnetic or superparamagnetic metal oxides. 
     
     
         6 . A method for producing an MRI contrast agent derived from nanoparticle that is porous first metal-doped second metal oxide nanoparticle with a central cavity, comprising the following steps:
 A) synthesizing first metal oxide nanoparticles under inert gas environment;   B) forming an epitaxial layer of second metal oxide on the surface of first metal oxide nanoparticles under inert gas environment;   C) maintaining the formation of the layer of second metal oxide under dry air environment;   D) removing the first metal oxide phase by treatment with acidic liquid at high temperature to form first metal oxide-doped second metal oxide nanoparticles having a central cavity; and   E) coating the nanoparticles with a biocompatible polymer.   
     
     
         7 . The method for producing an MRI contrast agent according to  claim 6 , wherein the first metal oxide is at least one selected from the group consisting of manganese oxide, cobalt oxide and zinc oxide. 
     
     
         8 . The method for producing an MRI contrast agent according to  claim 7 , wherein the first metal oxide is synthesized with at least one shape selected from the group consisting of octahedral, cross-shaped, urchin-shaped, and cubic. 
     
     
         9 . The method for producing an MRI contrast agent according to  claim 6 , wherein the second metal oxide is paramagnetic or superparamagnetic metal oxides. 
     
     
         10 . The method for producing an MRI contrast agent according to  claim 9 , wherein the paramagnetic or superparamagnetic metal oxides are at least one selected from the group consisting of iron oxide, chromium oxide, gadolinium oxide, cobalt oxide and nickel oxide. 
     
     
         11 . The method for producing an MRI contrast agent according to  claim 6 , wherein the layer of second metal oxide has a porous structure. 
     
     
         12 . The method for producing an MRI contrast agent according to  claim 6 , wherein the layer of second metal oxide comprises the doped first metal ions. 
     
     
         13 . The method for producing an MRI contrast agent according to  claim 6 , wherein the acidic liquid used in removing the first metal oxide phase is at least one selected from the group consisting of organic acids such as oleic acid and palmitic acid, and acidic buffers. 
     
     
         14 . The method for producing an MRI contrast agent according to  claim 6 , wherein the first metal oxide-doped second metal oxide nanoparticles are formed with a central cavity having at least one shape selected from the group consisting of octahedral, cross-shaped, urchin-shaped, and cubic. 
     
     
         15 . The method for producing an MRI contrast agent according to  claim 6 , wherein the biocompatible polymer is at least one selected from the group consisting of biopolymers such as chitosan, elastin, hyaluronic acid, alginate, gelatin, collagen, and cellulose; and synthetic polymers such as polyethylene glycol (PEG), polyethylene oxide (PEO), polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid (PLGA), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), polydioxanone (PDO), poly(L-lactide-co-caprolactone), poly(ester urethane) (PEU), poly(L-lactide-co-D-lactide), poly(ethylene-co-vinyl alcohol), poly(acrylic acid) (PAA), poly(vinyl alcohol) (PVA), polyvinylpyrrolidone (PVP), polystyrene (PS) and polyaniline (PAN). 
     
     
         16 . The method for producing an MRI contrast agent according to  claim 15 , wherein the biocompatible polymer can be modified by conjugation with targeting moieties or diagnostic moieties. 
     
     
         17 . The method for producing an MRI contrast agent according to  claim 16 , wherein the targeting moiety can be selected from the group consisting of antibodies, antibody fragments, aptamers, and various ligands binding to receptors displayed on the surface of target cell. 
     
     
         18 . The method for producing an MRI contrast agent according to  claim 16 , wherein the diagnostic moiety can be selected from the group consisting of diagnostic imaging moieties such as fluorophores, optical reporters and quantum dots; computed tomography (CT) probes such as iodine-based compounds and gold nanoparticles; and nonmetallic radioisotopes such as indium (In), technetium (Tc) and fluorine (F). 
     
     
         19 . A nanoparticle-based MRI contrast agent prepared by the method of  claim 6 . 
     
     
         20 . The nanoparticle-based MRI contrast agent according to  claim 19 , wherein the nanoparticle is a porous metal oxide nanoparticle. 
     
     
         21 . The nanoparticle-based MRI contrast agent according to  claim 20 , wherein the porous metal oxide is paramagnetic or superparamagnetic metal oxides. 
     
     
         22 . The nanoparticle-based MRI contrast agent according to  claim 21 , wherein the paramagnetic or superparamagnetic metal oxides are at least one selected from the group consisting of iron oxide, chromium oxide, gadolinium oxide, cobalt oxide and nickel oxide. 
     
     
         23 . The nanoparticle-based MRI contrast agent according to  claim 21 , wherein the paramagnetic or superparamagnetic metal oxides are formed with a central cavity having at least one shape selected from the group consisting of octahedral, cross-shaped, urchin-shaped, and cubic. 
     
     
         24 . The nanoparticle-based MRI contrast agent according to  claim 21 , wherein the paramagnetic or superparamagnetic metal oxides comprise the doped metal ions different from the metal of the paramagnetic or superparamagnetic metal oxides. 
     
     
         25 . A first metal oxide-doped second metal oxide nanoparticles comprising a central cavity prepared by the method of  claim 6 . 
     
     
         26 . The first metal oxide-doped second metal oxide nanoparticles according to  claim 25 , wherein the second metal oxide is paramagnetic or superparamagnetic metal oxides. 
     
     
         27 . The first metal oxide-doped second metal oxide nanoparticles according to  claim 26 , wherein the paramagnetic or superparamagnetic metal oxides are at least one selected from the group consisting of iron oxide, chromium oxide, gadolinium oxide, cobalt oxide and nickel oxide. 
     
     
         28 . The first metal oxide-doped second metal oxide nanoparticles according to  claim 25 , wherein the central cavity have at least one shape selected from the group consisting of octahedral, cross-shaped, urchin-shaped, and cubic. 
     
     
         29 . The first metal oxide-doped second metal oxide nanoparticles according to  claim 25 , wherein the second metal oxide comprises the doped metal ions different from the metal of the second metal oxides. 
     
     
         30 . Adsorbent nanoparticle comprising first metal oxide-doped second metal oxide nanoparticles of  claim 25 . 
     
     
         31 . Catalyst support comprising first metal oxide-doped second metal oxide nanoparticles of  claim 25 . 
     
     
         32 . Catalyst comprising first metal oxide-doped second metal oxide nanoparticles of  claim 25 . 
     
     
         33 . Electrode comprising first metal oxide-doped second metal oxide nanoparticles of  claim 25 . 
     
     
         34 . Battery component comprising first metal oxide-doped second metal oxide nanoparticles of  claim 25 .

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