Bismuth-gadolinium nanoparticles

Patent metadata

Field	Value
Publication number	US-11590225-B2
Application number	US-201716467698-A
Country	US
Kind code	B2
Filing date	Dec 8, 2017
Priority date	Dec 8, 2016
Publication date	Feb 28, 2023
Grant date	Feb 28, 2023

Abstract

Provided herein are nanoparticle compositions (e.g., nanoparticle compositions comprising high atomic number ions) that are useful for imaging diseases in a subject as well as radiosensitizing a disease in a subject (e.g., radiosensitizing a cancer in the subject). Methods of imaging a subject, methods of treating cancer, and processes of preparing the nanoparticle compositions are also provided.

First claim

What is claimed is:

1. A composition, comprising:
a nanoparticle core comprising one or more first linking groups covalently bonded to a first ligand and one or more second linking groups covalently bonded to a second ligand;
wherein one or more of the first ligands are complexed to Gd 3+ ions and one or more of the second ligands are complexed to Bi 3+ ions,
wherein the nanoparticle core is a silica core or a polysiloxane core,
wherein the first ligand is selected from 1,4,7,10-tetraazacyclododececane, 1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and the second ligand is selected from 1,4,7,10-tetraazacyclododececane, 1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); and
wherein the composition comprises a ratio of Gd 3+ ions:Bi 3+ ions of from about 1:1 to about 2:1.

2. The composition of claim 1 , wherein the one or more first linking groups each comprise a C 1-10 alkylamine covalently bonded to the first ligand.

3. The composition of claim 1 , wherein the one or more second linking groups each comprise a C 1-10 alkylamine covalently bonded to the second ligand.

4. The composition of claim 1 , wherein greater than about 20% of the first ligands are complexed to the Gd 3+ ions; or greater than about 20% of the second ligands are complexed to the Bi 3+ ions; or greater than about 20% of the first ligands are complexed to the Gd 3+ ions and greater than about 20% of the second ligands are complexed to the Bi 3+ ions.

5. The composition of claim 1 , wherein the nanoparticle comprises from about 5 to about 15 Gd 3+ ions and from about 1 to about 10 Bi 3+ ions.

6. The composition of claim 1 , wherein the hydrodynamic diameter of the nanoparticle is from about 2 nm to about 8 nm.

7. The composition of claim 1 , wherein the composition is suitable for intravenous or nasal administration.

8. The composition of claim 1 , wherein the first ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and the second ligand is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).

9. The composition of claim 1 , wherein the first ligand is 1,4,7,10-tetraazacyclododececane, 1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA and the second ligand is 1,4,7,10-tetraazacyclododececane, 1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA).

Assignees

• Brigham & Womens Hospital Inc
• Univ Claude Bernard Lyon
• Nh Theraguix
• Centre Nat Rech Scient

Inventors

• Berbeco Ross
• Thomas Eloise
• Lux Francois
• Tillement Olivier
• Detappe Alexandre
• Duc Geraldine Le

Classifications

• A61K41/0038 Primary

  Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10) · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K49/049

  Surface-modified nanoparticles, e.g. immune-nanoparticles · CPC title

• A61K49/108

  the metal complex being Gd-DOTA · CPC title

• A61K9/5146

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title