Nanoparticles and nanoparticle compositions
The invention provides multivalent surface-crosslinked micelle (SCM) particles, crosslinked reverse micelle (CRM) particles, and methods of making and using them. The SCM particles can be used, for example, to inhibit a virus or bacteria from binding to a host cell. The inhibition can be used in therapy for the flu, cancer, or AIDS. The CRM particles can be used, for example, to prepare metal nanoparticles or metal alloy nanoparticles, or they can be used in catalytic reactions.
1. An organic particle comprising a plurality of non-polymeric crosslinked amphiphiles;
wherein the non-polymeric crosslinked amphiphile comprises one or more nonpolar (C 6 -C 60 )alkyl or (C 6 -C 50 )fluoroalkyl chains and one or more polar head groups;
the nonpolar chains are located on the exterior of the particle and the polar head groups are oriented toward the interior of the particle; and
the amphiphiles are covalently crosslinked to each other near the head groups through thioether groups comprising an ammonium group bonded thereto.
2. The organic particle of claim 1 , wherein the particle comprises one or more metal salts or metal particles within the organic particle.
3. The organic particle of claim 2 , wherein the metal salt comprises AuCl 4 − , PtCl 6 2− , PdCl 4 2− , or a combination thereof.
4. The organic particle of claim 1 , wherein the particle comprises one or more catalytically active groups oriented toward the interior of the particle.
5. The organic particle of claim 4 , wherein the catalytically active groups are chosen from a carboxylic acid, sulfonic acid, amine, thiol, or a combination thereof.
6. The organic particle of claim 1 , comprising about 10 to about 150 of the non-polymeric crosslinked amphiphiles.
7. The organic particle of claim 1 , wherein the non-polar tail groups comprise an ester, imine, boronate, disulfide, salt bridge, or a combination thereof linking a portion of the tail to a head group of the amphiphile or another portion of the tail that is linked to the head group of the amphiphile.
8. The organic particle of claim 1 , wherein the non-polar tail groups of the amphiphile comprises one or more (C 6 -C 22 )alkyl groups, (C 6 -C 22 )fluoroalkyl groups, or a combination thereof.
9. The organic particle of claim 1 , wherein the particle is in the form of a liposome comprising a bilayer of the amphiphiles, and the bilayer comprises one or more water compartments between the bilayer of the amphiphiles.
10. The organic particle of claim 1 , wherein the particle comprises one or more cargo molecules within the particle or at the surface of the particle.
11. The organic particle of claim 10 , wherein the cargo molecules comprise one or more of a drug, an organic nanoparticle, an inorganic nanoparticle, a fluorophore, a diagnostic agent, and a catalyst.
12. The organic particle of claim 1 , wherein the crosslinking is cleavable by heat, by a change in pH, by a reducing agent, or by a combination thereof.
13. A delivery system comprising a plurality of the organic particles of claim 1 and a pharmaceutically acceptable diluent or carrier.
14. A therapeutic method comprising:
administering to a patient in need of therapy an effective amount of the delivery system of claim 13 , wherein the crosslinking of the particles encapsulates one or more drugs, such that the crosslinking of the particles is cleaved in vivo and the drug is thereby released into the body of the patient.
15. A method for preparing the organic particle comprising the crosslinked non-polymeric organic amphiphiles of claim 1 , the method comprising:
combining a plurality of non-polymeric amphiphiles, water, and an organic solvent, to form a noncovalently-associated self-assembled structure, wherein the non-polymeric amphiphile comprises a polar head group and a non-polar tail group;
combining the self-assembled structure with a crosslinking agent, wherein
a) the crosslinking agent comprises two or more thiol groups and the polar head group of the non-polymeric amphiphile comprises two or more alkenyl groups,
b) the crosslinking agent comprises two or more alkenyl groups and the polar head group of the non-polymeric amphiphile comprises two or more thiol groups,
inducing thiol-ene addition between the alkenyl groups and the thiol groups to covalently crosslink the amphiphiles to each other near the head groups through the formation of thioether groups to form the organic particle.
16. The method of claim 15 , wherein the crosslinking agent comprises two or more thiol groups and the polar head group of the non-polymeric amphiphile comprises two or more alkenyl groups.
17. The method of claim 15 , wherein the crosslinking agent comprises two thiol groups and the polar head group of the non-polymeric amphiphile comprises a triallylammonium group.
18. The method of claim 15 , wherein the amphiphiles are in the presence of one or more cargo molecules, and the cargo molecules are encapsulated in the hydrophilic core upon formation of the self-assembled structure.
19. A method of forming a metal nanoparticle comprising:
contacting a metal salt and a plurality of particles of claim 1 in an aqueous/organic solvent mixture, thereby extracting metal ions of the metal salt into the organic solvent, wherein the metal ions migrate to the interior of the particle, to provide a crosslinked organic particle encapsulating metal ions; and
contacting the crosslinked organic particle encapsulating metal ions with a reducing agent, thereby reducing the metal ions in the interior of the crosslinked organic particle, to provide the metal nanoparticle.
20. The method of claim 19 , wherein more than one type of metal salt is contacted with the crosslinked organic particle and the metal nanoparticle formed is an alloy.
21. The organic particle of claim 1 , wherein the ammonium group has the structure: