Labelled silica-based nanomaterial with enhanced properties and uses thereof

Abstract

The present invention relates to labelled silica-based nanoparticles with enhanced properties, to process for preparing them and to uses thereof.

1 . A method for making a nanoparticle comprising a core and a first label, comprising the steps of:
 (a) providing a first label bound to a first molecule comprising silane thereby forming a silane functionalized label;   (b) providing a first solution comprising free silicon-containing molecules;   (c) mixing the silane functionalized label and the first solution to form a first mixed solution;   (d) reducing the pH of the first mixed solution thereby allowing conditions for the formation of covalent bonds among the silicon-containing molecules to form silica within which the first label is covalently bound, thereby nucleating the core; and   (e) allowing sufficient time for the core to grow until stopped.   
     
     
         2 . The method of  claim 1 , wherein step (d) includes adding an ion-exchange resin to the first mixed solution, thereby to reduce the pH. 
     
     
         3 . The method of  claim 1 , wherein the silane comprises APTES, APTMS, MPTMS, and/or MPTES. 
     
     
         4 . The method of  claim 1 , wherein the method further comprises:
 (f) mixing the grown core with a second solution comprising free silicon-containing molecules to form a second mixed solution;   (g) reducing the pH of the second mixed solution thereby growing a shell; and   (h) allowing sufficient time for the shell to grow until stopped.   
     
     
         5 . The method of  claim 4 , wherein the second solution further comprises a second label. 
     
     
         6 . The method of  claim 4 , wherein steps (f) through (h) are repeated one or more times, and wherein the second solution comprises a label different than the first or preceding labels during each repeat. 
     
     
         7 . The method of  claim 4 , further comprising the steps of (i) optionally adding a functionalizing agent surrounding the shell to form a functionalized shell, and (j) tuning one or more properties of the nanoparticle by grafting one or more surface molecules to the shell or, if present to the functionalized shell. 
     
     
         8 . The method of  claim 7 , wherein the functionalizing agent comprises silanes, maleimides, thiols, and/or amines. 
     
     
         9 . The method of  claim 7 , wherein the surface molecules comprise a polymer, protein, antibody, antigen, sugar, PEG, organic molecule, and/or enzyme. 
     
     
         10 . The method of  claim 1 , wherein the free silicon-containing molecules comprise sodium trisilicate, sodium orthosilicate, sodium pyrosilicate, or hydrates thereof. 
     
     
         11 . The method of  claim 1 , wherein growth of the core and/or the shell is stopped by depletion of a constituent, addition of a quenching reagent, changing temperature, and/or changing pH. 
     
     
         12 - 44 . (canceled)