Functionalized Magnetic Nanoparticles and Methods of Use Thereof

Abstract

The present disclosure provides compositions comprising 2-deoxyglucose-functionalized magnetic nanoparticles. The compositions are useful in various applications, which are also provided.

1 . A pharmaceutical composition comprising:
 a) a functionalized magnetic nanoparticle (MNP) comprising at least one functional moiety, wherein the at least one functional moiety comprises 2-deoxyglucose, and wherein the functionalized MNP exhibits differential affinity and/or metabolic uptake into a mammalian tissue;   wherein the magnetic nanoparticle comprises a magnetic core particle and a biocompatible substrate, and wherein the 2DG is linked to the biocompatible substrate;   wherein the 2DG is linked to the biocompatible substrate via the 1-OH oxygen, the 3-OH oxygen, the 4-OH oxygen of 2DG, or via a carbon atom of 2DG; and   b) a pharmaceutically acceptable carrier.   
     
     
         2 . (canceled) 
     
     
         3 . The composition of  claim 1 , wherein the biocompatible substrate is dextran, an iron-dextran complex, a polysaccharide, polyethylene glycol, a polyethylene oxide, starch, a phospholipid, a poloxamer, a poloxamine, a silicone, a polyvinyl alcohol, or albumin. 
     
     
         4 - 6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein the functionalized MNP has a diameter of from about 10 nm to about 300 nm. 
     
     
         8 . The composition of  claim 1 , wherein said functionalized magnetic nanoparticle is capable, when injected into the bloodstream of a mammalian subject, of crossing the blood-brain barrier of said subject. 
     
     
         9 . The composition of  claim 1 , wherein the tissue is a diseased tissue. 
     
     
         10 . The composition of  claim 9 , wherein the level of metabolic uptake of the functionalized MNP by the diseased tissue is less than the level of metabolic uptake of the functionalized MNP by normal tissue. 
     
     
         11 . The composition of  claim 10 , wherein the diseased tissue is a plaque associated with Alzheimer's Disease, a tissue affected by Huntington's Disease, a tissue affected by Parkinson's Disease, a diseased cardiac tissue, a tissue affected by amyotrophic lateral sclerosis. 
     
     
         12 . The composition of  claim 9 , wherein the level of metabolic uptake of the functionalized MNP by the diseased tissue is greater than the level of metabolic uptake of the functionalized MNP by normal tissue. 
     
     
         13 . The composition of  claim 12 , wherein the tissue is a cancerous tissue. 
     
     
         14 . The composition of  claim 12 , wherein the tissue is an epileptigenic tissue. 
     
     
         15 . The composition of  claim 1 , wherein the functionalize MNP comprises at least a second functional moiety. 
     
     
         16 . The composition of  claim 15 , wherein the second functional moiety comprises a therapeutic agent. 
     
     
         17 . A method of detecting a tissue in a living mammalian subject, the method comprising
 a) administering to a mammalian subject a composition according to  claim 1 , wherein the functionalized MNP exhibits differential affinity for, and/or metabolic uptake into, a tissue in the mammalian subject; and   b) detecting the presence of the functionalized MNP in association with the tissue.   
     
     
         18 . The method of  claim 17 , wherein the tissue is a diseased tissue. 
     
     
         19 . The method of  claim 18 , wherein the level of metabolic uptake of the functionalized MNP by the diseased tissue is less than the level of metabolic uptake of the functionalized MNP by normal tissue. 
     
     
         20 . The method of  claim 19 , wherein the diseased tissue is a plaque associated with Alzheimer's Disease, a tissue affected by Huntington's Disease, a tissue affected by Parkinson's Disease, a diseased cardiac tissue, and a tissue affected by amyotrophic lateral sclerosis. 
     
     
         21 . The method of  claim 18 , wherein the level of metabolic uptake of the functionalized MNP by the diseased tissue is greater than the level of metabolic uptake of the functionalized MNP by normal tissue. 
     
     
         22 . The method of  claim 21 , wherein the tissue is a cancerous tissue or an epileptic lesion. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 17 , wherein the functionalized MNP further comprises at least a second functional moiety. 
     
     
         25 . The method of  claim 24 , wherein the second functional moiety comprises a therapeutic agent. 
     
     
         26 . The method of  claim 17 , wherein said detecting comprises magnetic resonance imaging or computed tomography. 
     
     
         27 . (canceled) 
     
     
         28 . A method of treating a disease in an individual, the method comprising administering a composition according to  claim 16  to the individual, wherein the functionalized MNP exhibits differential affinity for, and/or differential metabolic uptake into, a diseased tissue associated with the disease, and wherein the therapeutic agent treats the disease. 
     
     
         29 . The method of  claim 28 , wherein the diseased tissue is an epileptic lesion, and the therapeutic agent is an anti-seizure agent. 
     
     
         30 . The method of  claim 28 , wherein the diseased tissue is a tissue affected by Parkinson's Disease, and wherein the therapeutic agent is L-DOPA. 
     
     
         31 . The method of  claim 30 , wherein the diseased tissue is a tissue affected by Alzheimer's Disease, and wherein the therapeutic agent is donepezil HCl, rivastigmine, galantamine, memantine, or tacrine. 
     
     
         32 . The method of  claim 28 , wherein the diseased tissue is a cancerous tissue, and the therapeutic agent is an anti-cancer agent. 
     
     
         33 - 35 . (canceled)