Method for preparing surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media
View Patent ↗Water-dispersible nanoparticles are prepared by applying a coating of a amphipathic dispersant to the surface of a hydrophobic nanoparticle comprised of a semiconductive or metallic material. The amphipathic dispersant 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 a hydrophobic backbone and a plurality of alkyl acrylamide side chains, wherein the alkyl group of each acrylamide side chain has more than four carbon atoms, (ii) a plurality of hydrophobic nanoparticles, wherein the nanoparticles are provided with a water-insoluble organic coating thereon, and (iii) a nonaqueous solvent, to provide an admixture of dispersant, discrete, hydrophobic nanoparticles, and solvent;
(b) subjecting the admixture to conditions effective to cause adsorption of the dispersant onto the water-insoluble organic coating on each of the hydrophobic nanoparticles, thereby providing a plurality of discrete, dispersant-coated nanoparticles; and
(c) transferring the plurality of dispersant-coated nanoparticles prepared in step (b) to an aqueous medium to provide a population of water-dispersible nanoparticles.
2. The method of claim 1 , wherein the polymer further comprises two or more hydrophilic regions that 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 admixture is treated with a base effective to ionize acidic groups.
5. The method of claim 4 , wherein the admixture is treated with 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 (a) comprises admixing the amphipathic dispersant and plurality of nanoparticles in a number ratio in the range of approximately 50:1 to approximately 5000:1.
8. The method of claim 1 , further including crosslinking the amphipathic dispersant adsorbed to the nanoparticles.
9. The method of claim 1 , wherein the plurality of hydrophobic nanoparticles comprises semiconductor nanocrystals.
10. The method of claim 1 , wherein the hydrophobic backbone of the polymer represents about 25 wt. % to about 90 wt. % of the polymer.
11. The method of claim 1 , further comprising admixing the hydrophobic nanoparticles with an amphipathic dispersant comprising a polymer having a hydrophobic backbone and a combination of hydrophobic and hydrophilic side chains.
12. The method of claim 11 , wherein step (a) comprises admixing the hydrophobic nanoparticles with an amphipathic dispersant, the dispersant comprising a polymer containing at least one ethylenically unsaturated C 3 -C 6 carboxylic acid monomer residue and a plurality of hydrophobic side chains.
13. The method of claim 1 , wherein step (a) comprises admixing the hydrophobic nanoparticles with an amphipathic dispersant that comprises a polymer with hydrophilic regions that comprise an ionizable moiety selected from the group consisting of a carboxylic acid, sulfonic acid, phosphonic acid and an amine substituent.
14. The method of claim 1 ,
wherein the polymer further contains a plurality of carboxylic acid groups.
15. The method of claim 1 , wherein the water-insoluble organic coating comprises a compound selected from a trialkyl phosphine, a trialkyl phosphine oxide and hexyldecylamine.
16. The method of claim 1 , wherein the amphipathic dispersant has a molecular weight of about 1000 to 5000.
17. The method of claim 1 , wherein the hydrophilic regions represent about 30 wt. % to 75 wt. % of the amphipathic dispersant.
18. The method of claim 1 , wherein the alkyl group of each acrylamide side chain has six or more carbon atoms.
19. The method of claim 18 , wherein the alkyl group of each acrylamide side chain has 6 to 12 carbon atoms.
20. The method of claim 1 , wherein the alkyl group of each acrylamide side chain has eight or more carbon atoms.
21. The method of claim 1 , wherein the plurality of side chains comprises octylacrylamide.
22. The method of claim 1 ,
wherein the polymer comprises acrylic acid and octylacrylamide side chains or methacrylic acid and octylacrylamide side chains.