Gold nanoparticle conjugates and uses thereof
Inventors
Boyes, Stephen G. • Rowe, Misty D. • Hotchkiss, Jay
Assignees
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Publication Number
US-9175015-B2
Publication Date
2015-11-03
Expiration 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.
Core Innovation
The invention relates to multifunctional gold nanoparticle conjugates in which a polymer is grafted onto a gold nanoparticle surface under non-reducing conditions and through more than one sulfur atom. The conjugate architecture supports polymer grafting while enabling subsequent attachment of functional agents.
The polymer grafting relies on sulfur-containing functional groups and RAFT-CTA chemistries, including dithioesters, trithiocarbonates, xanthates, and dithiocarbamates. The document presents permissible functional groups and linkers for further diversification of the resulting gold nanoparticle conjugates, including NAOS-containing copolymers and DATC-based RAFT chain transfer agents.
The invention further enables post-functionalization with therapeutic and targeting agents, and optionally imaging. The document describes that controlling polymer architecture, including brush versus mushroom configuration, modulates accessibility and loading/localization on the gold nanoparticle surface, with representative conjugation examples including folic acid, RGD, paclitaxel, and methotrexate.
Claims Coverage
The independent claim covers a gold nanoparticle conjugate defined by Formula (II) and a polymer grafted to the gold nanoparticle under non-reducing conditions through more than one sulfur atom. The claim set refines the grafting linkage and allows broad selections of functional groups, and certain dependent claims further add therapeutic, targeting, pharmaceutical composition, and optional imaging use contexts.
Non-reducing sulfur-based polymer grafting to gold nanoparticle surface
A gold nanoparticle conjugate comprising a polymer grafted onto a gold nanoparticle, the gold nanoparticle having the structure of Formula (II), wherein the surface of a gold nanoparticle is grafted to the polymer under non-reducing conditions and through more than one sulfur atom.
Thiocarbonylthio grafting linkage for polymer attachment
The gold nanoparticle conjugate is defined where the polymer contains a thiocarbonylthio moiety and the gold nanoparticle is grafted to the polymer via that thiocarbonylthio moiety.
RAFT chain transfer agent selection defining sulfur-containing polymer structure
A gold nanoparticle conjugate where the polymer includes one of specific chain transfer agents: dithioester, xanthate, dithiocarbamate, or trithiocarbonate.
Broad selectable functional group classes for further conjugation
A gold nanoparticle conjugate in which a functional group attached is selected from specified classes of functional groups including various acid, sulfonic acid, derivative, and other substituted organic groups.
Overall claim coverage centers on polymer grafted to gold nanoparticles under non-reducing, multi-sulfur attachment, with RAFT-CTA-defined sulfur-containing polymer architectures and broadly selectable functional groups. Dependent claims further specify particular grafting linkages and add therapeutic, targeting, and optional imaging contexts.
Stated Advantages
The conjugate architecture supports polymer grafting while enabling subsequent attachment of functional agents.
Controlling polymer architecture, including brush versus mushroom configuration, modulates accessibility and loading/localization on the gold nanoparticle surface.
In vitro testing indicates low cytotoxicity.
Agent-targeting efficacy testing is described.
Documented Applications
Post-functionalization with therapeutic agents and targeting agents, and optionally imaging.
Representative targeting and therapeutic conjugation examples include folic acid, RGD, paclitaxel, and methotrexate.
Grafting onto gold nanorods and gold nanoparticles.
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