Magnetic and fluorescent reverse nanoassemblies

Abstract

Disclosed are magnetic and fluorescent nanoassemblies having reverse architectures. Especially, the nanoassemblies include an organic fluorescent inner core and magnetic nanoparticles contacting the surface of the fluorescent core. The nanoassemblies may further be coated by a polymer adsorbed at its surface, the polymer being optionally functionalized. Also described is a process for manufacturing the nanoassemblies, as well as use of the nanoassemblies, especially for multimodal imaging; in vitro and/or in vivo diagnostics through multimodal imaging; ex vivo sensing and/or extraction; and/or therapy.

1 - 15 . (canceled) 
     
     
         16 . A nanoassembly comprising
 one organic fluorescent inner core comprising fluorescent organic molecules, and   magnetic nanoparticles contacting the surface of said fluorescent inner core;   
       provided that the nanoassembly does not comprise silica, functionalized silica, doped silica, grafted silica or a combination thereof. 
     
     
         17 . The nanoassembly according to  claim 16 , wherein the fluorescent organic molecules are compounds of Formula I, 
       
         
           
           
               
               
           
         
         wherein: 
         L represents a spacer selected from (i), (ii) and (iii) 
       
       
         
           
           
               
               
           
         
         X represents O, CH 2  or NR 8 , wherein R 8  represents H, alkyl or alkene; 
         X′ represents O or NR 9 , wherein R 9  represents H, alkyl or alkene; 
         n represents an integer selected from 1, 2, 3 and 4; 
         R 1  represents —CO 2 H or —P(O) (OH) 2 ; and 
         R 2 , R 3 , R 4 , R 5 , R 6  and R 7  represent each independently an optionally functionalized group selected from alkyl and ester and poly(ethylene glycol). 
       
     
     
         18 . The nanoassembly according to  claim 16 , wherein the magnetic nanoparticles are superparamagnetic nanoparticles selected from the group consisting of γ-Fe 2 O 3  and Fe 3 O 4 . 
     
     
         19 . The nanoassembly according to  claim 16 , having a hydrodynamic diameter ranging from 20 to 700 nm. 
     
     
         20 . The nanoassembly according to  claim 16 , wherein the fluorescent inner core comprises a number of organic fluorescent molecule ranging from 1×10 4  to 1×10 7 . 
     
     
         21 . The nanoassembly according to  claim 16 , comprising a number of magnetic nanoparticles ranging from 1×10 2  to 1×10 6 . 
     
     
         22 . The nanoassembly according to  claim 16 , comprising at least one polymer adsorbed at the surface of the nanoassembly. 
     
     
         23 . The nanoassembly according to  claim 22 , wherein the polymer is an ionic polymer. 
     
     
         24 . The nanoassembly according to  claim 22 , wherein the polymer is a polyelectrolyte. 
     
     
         25 . The nanoassembly according to  claim 22 , wherein the polymer is of Formula II, 
       
         
           
           
               
               
           
         
         wherein: 
         m represents a positive integer ranging from 20 to 150; 
         x, y and z represent each independently a percentage of m, ranging from 0% to 100% of m, wherein x+y+z is equal to 100% of m; 
         X represents —COOH, alkyl, aryl, —CO-alkyl, poly(ethylene glycol), or -poly(ethylene glycol)-OMe; Y represents —(C═O)—O-L-R 8 , —(C═O)—S-L-R 8 , —(C═O)—NH(-L-R 8 ) or —(C═S)—NH(-L-R 8 ), wherein:
 L 1  represents a spacer selected from alkyl, alkene, aryl, arylalkyl, poly(ethylene glycol) and poly(propylene glycol) linking groups having 1 to 150 chain atoms, wherein the linking group can be optionally interrupted or terminated by one or more —O—, —S—, —NR 9 —, —CO—, —NHCO—, —CONH— or a combination thereof, wherein R 9  is H or alkyl; and 
 R 8  represents a reactive group selected from N 3 , amino, alkylamino, COOH, amide, maleimide, alkene, alkyne, SH, OH, ester, activated ester, activated carboxylic acid, halo, nitro, nitrile, isonitriles, acrylamide, aldehyde, ketone, acetal, ketal, anhydride, glutaric anhydride, succinic anhydride, maleic anhydride, thiocyanate, isothiocyanate, isocyanate, hydrazide, hydrazine, hydrazone, ether, oxide, cyanate, diazo, diazonium, sulfide, disulfide, sulfoxide, sulfone, sulfonic acid, sulfinic acid, sulfate, sulfenic acid, amidine, imide, imidate, nitrone, hydroxylamine, oxime, hydroxamic acid, thiohydroxamic acid, allene, ortho ester, sulfite, enamine, ynamine, urea, pseudourea, semicarbazide, carbodiimide, carbamate, imine, acetylene, olefin, polyene, alkylacrylate, oxetane, ammonium, oxonium, phosphonium, sulfonium, positively charged and neutral metal complex; and 
 
         Z represents —(C═O)—O-L 2 -R 10 , —(C═O)—S-L 2 -R 10 , —(C═O)—NH(-L 2 -R 10 ) or —(C═S)—NH(-L 2 -R 10 ) wherein:
 L 2  represents a single bond or a spacer selected from alkyl, alkene, aryl, arylalkyl, poly(ethylene glycol) and poly(propylene glycol) linking groups having 1 to 150 chain atoms, wherein the linking group can be optionally interrupted or terminated by one or more —O—, —S—, —NR 9 —, —CO—, —NHCO—, —CONH— or a combination thereof, wherein R 9  is H or alkyl; optionally additionally comprising a residue of a reactive group through which L 2  is bonded to R 10 ; and 
 R 10  represents a bioactive group selected from amino acid, peptide, protein, antibody, affinity protein, enzyme, polysaccharide, dextran, benzylguanine, lipid, lipid assembly, fatty acid, nucleoside, nucleotide, oligonucleotide, hapten, aptamer, ligand, antibiotic, substrate, biotin, avidin, streptavidin, synthetic polymer, poly(ethylene glycol), poly(propylene glycol), polymeric microparticle, nanoparticle, fluorophore, chromophore, radioisotope, macrocyclic complexes of radioisotope, and combinations thereof. 
 
       
     
     
         26 . The nanoassembly according to  claim 22 , wherein the polymer is poly(acrylic acid). 
     
     
         27 . A process for manufacturing nanoassemblies according  claim 16 , comprising injecting a solution of fluorescent organic molecules into a dispersion of magnetic nanoparticles under stirring. 
     
     
         28 . The process according to  claim 27 , comprising a subsequent step of addition of at least one polymer. 
     
     
         29 . The process according to  claim 28 , further comprising a subsequent step of functionalization of the polymer by a bioactive group. 
     
     
         30 . A pharmaceutical composition comprising nanoassemblies according to  claim 16 , in combination with at least one pharmaceutically acceptable vehicle. 
     
     
         31 . Use of nanoassemblies according to  claim 16 , to extract and detect molecules and/or biological targets from physiological medium.