Gold Nanoparticle Conjugates and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2016017065-A1
Application number	US-201514867165-A
Country	US
Kind code	A1
Filing date	Sep 28, 2015
Priority date	Aug 22, 2007
Publication date	Jan 21, 2016
Grant date	—

Abstract

The disclosure generally relates to formation of polymers grafted to or polymerized from the surface of gold nanoparticles. The polymers are functionalized to include therapeutic agents and/or targeting agents at their surface, thereby allowing both therapeutic and targeting compounds to be directed to specific cells in a patient.

First claim

What is claimed is:

1 . A method of making a gold nanoparticle conjugate comprising:
contacting a trithiocarbonate of the following formula

with an alkene of the following formula

to produce a polymer of the following formula

and
contacting the polymer with a gold nanoparticle to form the gold nanoparticle conjugate,
wherein R 1 , R 2 , R 3 , and R 4 are each independently selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, acylamino, substituted acylamino, alkylamino, substituted alkylamino, alkylsulfinyl, substituted alkylsulfinyl, alkylsulfonyl, substituted alkylsulfonyl, alkylthio, substituted alkylthio, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryloxy, substituted aryloxy, aryloxycarbonyl, substituted aryloxycarbonyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, dialkylamino, substituted dialkylamino, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroalkyloxy, substituted heteroalkyloxy, heteroaryloxy and substituted heteroaryloxy.

2 . The method of claim 1 , wherein the gold nanoparticle conjugate has the following formula

represents the surface of the gold nanoparticle.

3 . The method of claim 1 , wherein the trithiocarbonate and alkene are contacted under non-reducing conditions.

4 . The method of claim 1 , wherein the polymer and gold nanoparticle are contacted under non-reducing conditions.

5 . The method of claim 1 , wherein the polymer and gold nanoparticle are associated through more than one sulfur atom.

6 . The method of claim 1 , wherein the gold nanoparticle conjugate further comprises a functional group.

7 . The method of claim 6 , wherein the functional group is selected from the group consisting of carboxylic acids and carboxylic acid salt derivatives, acid halides, sulfonic acids and sulfonic acid salts, anhydride derivatives, hydroxyl derivatives, amine and amide derivatives, silane derivations, phosphate derivatives, nitro derivatives, succinimide and sulfo-containing succinimide derivatives, halide derivatives, alkene derivatives, morpholine derivatives, cyano derivatives, epoxide derivatives, ester derivatives, carbazole derivatives, azide derivatives, alkyne derivatives, acid containing sugar derivatives, glycerol analogue derivatives, maleimide derivatives, protected acids and alcohols, and acid halide derivatives.

8 . The method of claim 1 , wherein the gold nanoparticle conjugate further comprises a therapeutic agent covalently bonded to the polymer.

9 . The method of claim 1 , wherein the gold nanoparticle conjugate further comprises a targeting agent covalently bonded to the polymer.

10 . A method of making a gold nanoparticle conjugate comprising:
contacting a compound of the following formula

with an alkene of the following formula

to produce a polymer of the following formula

and
contacting the polymer with a gold nanoparticle to form the gold nanoparticle conjugate,
wherein R 1 , R 2 , R 3 , and R 4 are each independently selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, acylamino, substituted acylamino, alkylamino, substituted alkylamino, alkylsulfinyl, substituted alkylsulfinyl, alkylsulfonyl, substituted alkylsulfonyl, alkylthio, substituted alkylthio, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryloxy, substituted aryloxy, aryloxycarbonyl, substituted aryloxycarbonyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, dialkylamino, substituted dialkylamino, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroalkyloxy, substituted heteroalkyloxy, heteroaryloxy and substituted heteroaryloxy.

11 . The method of claim 10 , wherein the compound is a dithioester, xanthate, or dithiocarbamate.

12 . The method of claim 10 , wherein the gold nanoparticle conjugate has the following formula

represents the surface of the gold nanoparticle.

13 . The method of claim 10 , wherein the compound and alkene are contacted under non-reducing conditions.

14 . The method of claim 10 , wherein the polymer and gold nanoparticle are contacted under non-reducing conditions.

15 . The method of claim 10 , wherein the polymer and gold nanoparticle are associated through more than one sulfur atom.

16 . The method of claim 10 , wherein the gold nanoparticle conjugate further comprises a functional group.

17 . The method of claim 16 , wherein the functional group is selected from the group consisting of carboxylic acids and carboxylic acid salt derivatives, acid halides, sulfonic acids and sulfonic acid salts, anhydride derivatives, hydroxyl derivatives, amine and amide derivatives, silane derivations, phosphate derivatives, nitro derivatives, succinimide and sulfo-containing succinimide derivatives, halide derivatives, alkene derivatives, morpholine derivatives, cyano derivatives, epoxide derivatives, ester derivatives, carbazole derivatives, azide derivatives, alkyne derivatives, acid containing sugar derivatives, glycerol analogue derivatives, maleimide derivatives, protected acids and alcohols, and acid halide derivatives.

18 . The method of claim 10 , wherein the gold nanoparticle conjugate further comprises a therapeutic agent covalently bonded to said polymer.

19 . The method of claim 10 , wherein the gold nanoparticle conjugate further comprises a targeting agent covalently bonded to said polymer.

Assignees

• Colorado School Of Mines

Inventors

• Boyes Stephen G
• Rowe Misty D
• Hotchkiss Jay

Classifications

• A61K49/1818

  particles, e.g. uncoated or non-functionalised microparticles or nanoparticles · CPC title

• A61K47/58

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/0054

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title