US 8,574,549 B2Granted

Nanoparticle contrast agents for diagnostic imaging

AssigneeGeneral Electric Company

InventorsMatthew David Butts, Robert Edgar Colborn, Peter John Bonitatibus, Jr., Amit Mohan Kulkarni, Bruce Allan Hay, Andrew Soliz Torres, Brian Christopher Bales, Michacl Ernest Marino

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Abstract

Compositions of nanoparticles functionalized with at least one zwitterionic moiety, methods for making a plurality of nanoparticles, and methods of their use as diagnostic agents are provided. The nanoparticles have characteristics that result in minimal retention of the particles in the body compared to other nanoparticles. The nanoparticle comprises a core, having a core surface essentially free of silica, and a shell attached to the core surface. The shell comprises at least one silane-functionalized zwitterionic moiety.

Claims19

Dependent claims

A method comprising:

administering a diagnostic agent composition to a subject, wherein the diagnostic agent composition comprises a plurality of nanoparticles,
wherein the nanoparticle comprises a core, having a core surface essentially free of silica;
and
a shell attached to the core surface;
wherein the shell comprises at least one silane-functionalized zwitterionic moiety, wherein the silane functionalized zwitterionic moiety comprises a silane moiety and a zwitterionic moiety, and wherein the silane moiety is covalently bonded to the zwitterionic moiety via a spacer comprising less than 10 carbon atoms;
and
wherein the silane-functionalized zwitterionic moieties are bound to the core at the core surface without any intervening silica layer;
wherein the silane functionalized zwitterionic moiety comprises a hydrolysis product of a precursor tri-alkoxy silane wherein the precursor tri-alkoxy silane is selected from a group consisting of N,N-dimethyl-3-sulfo-N-(3-(trimethoxysilyl)propyl)propan-1-aminium, 3-(methyl(3-(trimethoxysilyl)propyl)amino) propane-l-sulfonic acid, 3-(3-(trimethoxysilyl) 5 propylamino)propane-1-sulfonic acid, 2-(2-(trimethylsilyl)ethoxy(hydroxy)phosphoryloxy)-N,N,N-trimethylethanaminium, 2-(2-(trimethoxysilyl)ethyl(hydroxy)phosphoryloxy)-N,N,N-trimethylethanaminium, N,N,N-trimethyl-3-(N-3-(trimethoxysilyl)propionylsulfamoyl) propan-1-aminium, N-((2H-tetrazol-5-yl)methyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, N-10(2-carboxyethyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, 3-(methyl(3-(trimethoxysilyl)propyl)amino)propanoic acid, 3-(3-(trimethoxysilyl)propylamino)propanoic acid, N-(carboxymethyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, 2-(methyl(3-(trimethoxysilyl)propyl)amino)acetic acid, 2-(3-(trimethoxysilyl)propylamino)acetic acid, 2-(4-(3-(trimethoxysilyl)propylcarbamoyl)15 piperazin-1-yl)acetic acid, 3-(4-(3-(trimethoxysilyl)propylcarbamoyl)piperazin-1-yl) propanoic acid, 2-(methyl(2-(3-(trimethoxysilyl) propylureido)ethyl)amino)acetic acid, 2-(2-(3-(trimethoxysilyl)propylureido)ethyl)amino acetic acid, and combinations thereof and
imaging the subject with a diagnostic device.

6 more elements

A method comprising:

administering a diagnostic agent composition to a subject, wherein the diagnostic agent composition comprises a plurality of nanoparticles,
wherein the nanoparticle comprises a core, having a core surface essentially free of silica;
and
a shell attached to the core surface;
wherein the shell comprises at least one silane-functionalized zwitterionic moiety, wherein the silane functionalized zwitterionic moiety comprises a silane moiety and a zwitterionic moiety, and wherein the silane moiety is covalently bonded to the zwitterionic moiety;
and
wherein the silane-functionalized zwitterionic moieties are bound to the core at the core surface without any intervening silica layer;
wherein the silane functionalized zwitterionic moiety comprises a hydrolysis product of a precursor tri-alkoxy silane wherein the precursor tri-alkoxy silane is selected from a group consisting of N,N-dimethyl-3-sulfo-N-(3-(trimethoxysilyl)propyl)propan-1-aminium, 3-(methyl(3-(trimethoxysilyl)propyl)amino) propane-l-sulfonic acid, 3-(3-(trimethoxysilyl) 5 propylamino)propane-1-sulfonic acid, 2-(2-(trimethylsilyl)ethoxy(hydroxy)phosphoryloxy)-N,N,N-trimethylethanaminium, 2-(2-(trimethoxysilyl)ethyl(hydroxy)phosphoryloxy)-N,N,N-trimethylethanaminium, N,N,N-trimethyl-3-(N-3-(trimethoxysilyl)propionylsulfamoyl) propan-1-aminium, N-((2H-tetrazol-5-yl)methyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, N-10(2-carboxyethyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, 3-(methyl(3-(trimethoxysilyl)propyl)amino)propanoic acid, 3-(3-(trimethoxysilyl)propylamino)propanoic acid, N-(carboxymethyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, 2-(methyl(3-(trimethoxysilyl)propyl)amino)acetic acid, 2-(3-(trimethoxysilyl)propylamino)acetic acid, 2-(4-(3-(trimethoxysilyl)propylcarbamoyl)15 piperazin-1-yl)acetic acid, 3-(4-(3-(trimethoxysilyl)propylcarbamoyl)piperazin-1-yl) propanoic acid, 2-(methyl(2-(3-(trimethoxysilyl) propylureido)ethyl)amino)acetic acid, 2-(2-(3-(trimethoxysilyl)propylureido)ethyl)amino acetic acid, and combinations thereof and
wherein the nanoparticle does not contain a targeting ligand;
and
imaging the subject with a diagnostic device.

8 more elements

A method comprising:

administering a diagnostic agent composition to a subject, wherein the diagnostic agent composition comprises a plurality of nanoparticles,
wherein the nanoparticle comprises a core, having a core surface essentially free of silica;
and
a shell attached to the core surface;
wherein the shell comprises at least one silane-functionalized zwitterionic moiety, wherein the silane functionalized zwitterionic moiety comprises a silane moiety and a zwitterionic moiety, and wherein the silane moiety is covalently bonded to the zwitterionic moiety;
and
wherein the silane-functionalized zwitterionic moieties are bound to the core at the core surface without any intervening silica layer;
wherein the silane functionalized zwitterionic moiety comprises a hydrolysis product of a precursor tri-alkoxy silane wherein the precursor tri-alkoxy silane is selected from a group consisting of N,N-dimethyl-3-sulfo-N-(3-(trimethoxysilyl)propyl)propan-1-aminium, 3-(methyl(3-(trimethoxysilyl)propyl)amino) propane-l-sulfonic acid, 3-(3-(trimethoxysilyl) 5 propylamino)propane-1-sulfonic acid, 2-(2-(trimethylsilyl)ethoxy(hydroxy)phosphoryloxy)-N,N,N-trimethylethanaminium, 2-(2-(trimethoxysilyl)ethyl(hydroxy)phosphoryloxy)-N,N,N-trimethylethanaminium, N,N,N-trimethyl-3-(N-3-(trimethoxysilyl)propionylsulfamoyl) propan-1-aminium, N-((2H-tetrazol-5-yl)methyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, N-10(2-carboxyethyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, 3-(methyl(3-(trimethoxysilyl)propyl)amino)propanoic acid, 3-(3-(trimethoxysilyl)propylamino)propanoic acid, N-(carboxymethyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium, 2-(methyl(3-(trimethoxysilyl)propyl)amino)acetic acid, 2-(3-(trimethoxysilyl)propylamino)acetic acid, 2-(4-(3-(trimethoxysilyl)propylcarbamoyl)15 piperazin-1-yl)acetic acid, 3-(4-(3-(trimethoxysilyl)propylcarbamoyl)piperazin-1-yl) propanoic acid, 2-(methyl(2-(3-(trimethoxysilyl) propylureido)ethyl)amino)acetic acid, 2-(2-(3-(trimethoxysilyl)propylureido)ethyl)amino acetic acid, and combinations thereof and
a targeting ligand, wherein the zwitterionic moiety and the targeting ligand are not the same;
and
imaging the subject with a diagnostic device.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/344,608Filed 29 Dec 2008
Published: US 2010/0166666 A11 Jul 2010
Granted: 5 Nov 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

A61K 49/1848
Having a magnetic core coated or functionalised with a small organic molecule: the small organic molecule being a silane
A61K 49/0428
Nanoparticles, nanobeads, nanospheres, nanocapsules, i.e. having a size or diameter smaller than 1 micrometer: surface-modified nanoparticles,…
B82Y 5/00
Nanobiotechnology or nanomedicine
A61K
Medicines and medical preparations