Gadolinium expressed lipid nanoparticles for magnetic resonance imaging

Abstract

Lipid nanoparticles expressing metal ions and methods for using the compositions for magnetic resonance imaging.

1 . A nanoparticle, comprising:
 (a) a lipid;   (b) a polyalkylene-containing lipid; and   (c) a lipid-containing metal chelator,   wherein the nanoparticle is not a liposome.   
     
     
         2 . The nanoparticle of  claim 1 , wherein the lipid is selected from the group consisting of phospholipids, sphingolipids, cholesterol and steroid derivatives, bile acids and derivatives, cardilipin, acyl-glycerides and derivatives, glycolipids, acyl-peptides, and fatty acids. 
     
     
         3 . (canceled) 
     
     
         4 . The nanoparticle of  claim 1 , wherein the lipid is a phospholipid is selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); dipalmitoyl phosphatidylcholine; dimysristoyl phosphatidyl choline;
 dioleoyl phosphatidyl choline; trans-esterified phospholipids derived from eggs, soybean, flaxseed, and the like; and phosphatidylcholine substituted with phosphatidyl ethanolamine, phosphatidylglycerol, phosphatidyl serine, and phosphatidic acids.   
     
     
         5 . The nanoparticle of  claim 1 , wherein the polyalkylene-containing lipid is selected from the group consisting of polyoxyethylene-containing lipids and polyoxypropylene-containing lipids. 
     
     
         6 . The nanoparticle of  claim 1 , wherein the polyalkylene-containing lipid is a phospholipid functionalized with polyethylene glycol. 
     
     
         7 . (canceled) 
     
     
         8 . The nanoparticle of  claim 6 , wherein the phospholipid functionalized with polyethylene glycol is N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG-2000-DSPE). 
     
     
         9 . The nanoparticle of  claim 1 , wherein the lipid-containing metal chelator is selected from the group consisting of DSPE-BOPTA, DSPE-DO3A, DSPE-DOTA, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetyl (DSPE-DTPA), tetraazacyclododecane, tetraacety(gadodiamide)-PE, and lipid-functionalized-[N,N-bis[2-[bis(carboxymethyl)amino]-ethyl]-glycinato-(5″)]. 
     
     
         10 - 14 . (canceled) 
     
     
         15 . The nanoparticle of  claim 1  further comprising a targeting moiety. 
     
     
         16 . The nanoparticle of  claim 15 , wherein the targeting moiety is selected from the group consisting of a protein, a polypeptide, a peptide, an antibody or fragment thereof, a small molecule, a sugar or polysaccharide or derivative thereof, and a nucleic acid. 
     
     
         17 - 20 . (canceled) 
     
     
         21 . The nanoparticle of  claim 1  further comprising a chelated metal ion. 
     
     
         22 . (canceled) 
     
     
         23 . The nanoparticle of  claim 21  wherein the chelated metal ion is a paramagnetic metal ion. 
     
     
         24 . The nanoparticle of  claim 23 , wherein the paramagnetic metal ion is selected from the group consisting of Gd 3+ , Cu 2+ , Fe 3+ , Fe 2+ , and Mn 2+ . 
     
     
         25 . The nanoparticle of  claim 21 , wherein the chelated metal ion is an ion of a radio-isotope. 
     
     
         26 . The nanoparticle of  claim 25 , wherein the ion of a radio-isotope is selected from the group consisting of ions of  68 Ga,  55 Co,  86 Y,  90 Y,  177 Lu, and  111 In. 
     
     
         27 . A composition, comprising a carrier and a plurality of the nanoparticles of  claim 21 . 
     
     
         28 - 29 . (canceled) 
     
     
         30 . A method for imaging of tissues, comprising administering to a subject to be imaged an effective amount of the composition of  claim 23 . 
     
     
         31 . The method of  claim 30 , wherein the composition is administered subcutaneously or intravenously. 
     
     
         32 . (canceled) 
     
     
         33 . The method of  claim 30 , wherein the tissue is selected from the group consisting of lymphoid, cardiovascular, liver, kidney, brain, heart, muscle, and gastrointestinal tract tissues, and other tissues accessible by the lymphatic or vascular (blood) systems. 
     
     
         34 - 36 . (canceled) 
     
     
         37 . A method for delivering a radio-cancer therapeutic agent to a cancer cell, comprising administering to a cancer cell an effective amount of the composition of  claim 25 . 
     
     
         38 . The method of  claim 37 , wherein the composition is administered subcutaneously or intravenously. 
     
     
         39 . (canceled)