Method for preparing surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media

Abstract

Water-dispersible nanoparticles are prepared by applying a coating of a multiply amphipathic dispersant to the surface of a hydrophobic nanoparticle comprised of a semiconductive or metallic material. The multiply amphipathic dispersant has two or more hydrophobic regions and two or more hydrophilic regions, and is typically polymeric. Preferred polymeric dispersants are comprised of (1) a hydrophobic backbone with hydrophilic branches, (2) a hydrophilic backbone with hydrophobic branches, or (3) a backbone that may be either hydrophobic or hydrophilic, and substituted with both hydrophilic and hydrophobic branches. Monodisperse populations of water-dispersible nanoparticles are also provided, as are conjugates of the water-dispersible nanoparticles with affinity molecules such as peptides, oligonucleotides, and the like.

1 . A method for preparing a population of water-dispersible nanoparticles, comprising:
 (a) admixing (i) an amphipathic dispersant comprised of a polymer having two or more hydrophobic regions and two or more hydrophilic regions, with (ii) a plurality of hydrophobic nanoparticles, in (iii) a nonaqueous solvent, to provide an admixture of dispersant and nanoparticles in solution;   (b) subjecting the admixture to conditions effective to cause adsorption of the dispersant by the nanoparticles; and   (c) transferring the dispersant-coated nanoparticles prepared in step (b) to an aqueous medium.   
     
     
         2 . The method of  claim 1 , wherein the hydrophilic regions contain ionizable groups. 
     
     
         3 . The method of  claim 2 , wherein prior to step (b), the admixture is treated with an ionizing agent effective to ionize the ionizable groups. 
     
     
         4 . The method of  claim 3 , wherein the ionizable groups are acidic groups and the ionizing agent is a base. 
     
     
         5 . The method of  claim 4 , wherein the base is a nitrogenous base or an inorganic hydroxide. 
     
     
         6 . The method of  claim 1 , wherein step (b) comprises removal of the solvent from the admixture. 
     
     
         7 . The method of  claim 1 , wherein step (c) comprises adding water to the dried admixture. 
     
     
         8 . The method of  claim 1 , wherein the number ratio of the amphipathic dispersant to the plurality of nanoparticles in step (a) is in the range of approximately 50:1 to approximately 5000:1. 
     
     
         9 . The method of  claim 1 , further including crosslinking the amphipathic dispersant adsorbed to the nanoparticles.