Organic/inorganic hybrid nanoparticulates made from iron carboxylates

Patent metadata

Field	Value
Publication number	US-10738068-B2
Application number	US-201816046668-A
Country	US
Kind code	B2
Filing date	Jul 26, 2018
Priority date	Oct 1, 2007
Publication date	Aug 11, 2020
Grant date	Aug 11, 2020

Abstract

The invention relates to nanoparticles made from organometallic hybrid materials made from iron carboxylates, used for example as contrast agents. The particles can also be used for the encapsulation and vectoring of molecules of interest such as active pharmaceutical agents, cosmetically interesting compounds and markers. Apart from the intrinsic properties thereof for imaging, said nanoparticles give good results in terms of capacity of loading with medicaments and in biocompatibility.

First claim

The invention claimed is:

1. An isoreticular porous crystalline MOF nanoparticle comprising a three-dimensional succession of units having formula (I) below:
Fe m O k X l L p    Formula (I)

in which:
Fe represents the metallic ion Fe 3+ or Fe 2+ ;
m is 1 to 4;
k is 0 to 4;
l is 0 to 4;
p is 1 to 4;
X is a ligand selected from the group consisting of OH − , Cl − , F − , Br − , SO 4 2− , NO 3 − , ClO 4 − , PF 6 − , BF 3 − , R 1 —(COO) n − , R 1 —(SO 3 ) n − , and R 1 —(PO 3 ) n − , in which R 1 is a hydrogen atom or an optionally substituted, linear or branched C 1 to C 12 alkyl, and n=1 to 4;
L is a di-, tri-, or tetra-carboxylate ligand selected from the group consisting of:

in which:
each t independently is an integer from 1 to 4, and
each R L3 independently is H, a halogen, OH, NH 2 , NO 2 , or a C 1 to C 6 alkyl.

2. The nanoparticle as claimed in claim 1 , in which the ligand L is

wherein R L3 and t are as defined.

3. An isoreticular porous crystalline MOF nanoparticle comprising a three-dimensional succession of units having formula (I) below:
Fe m O k X l L p    Formula (I)

in which:
Fe represents the metallic ion Fe 3+ or Fe 2+ ;
m is 1 to 4;
k is 0 to 4;
l is 0 to 4;
p is 1 to 4;
X is a ligand selected from the group consisting of OH − , Cl − , F − , I − , Br − , SO 4 2− , NO 3 − , ClO 4 − , PF 6 − , BF 3 − , R 1 —(COO) n − , R 1 —(SO 3 ) n − , and R 1 —(PO 3 ) n − , in which R 1 is a hydrogen atom or an optionally substituted, linear or branched C 1 to C 12 alkyl, and n=1 to 4;

L is a di-, or tetra-carboxylate ligand selected from the group consisting of:

in which:
each t independently is an integer from 1 to 4, and
each R L3 independently is H, a halogen, OH, NH 2 , NO 2 or a C 1 to C 5 alkyl.

4. An isoreticular porous crystalline MOF nanoparticle comprising a three-dimensional succession of units having formula (I) below:
Fe m O k X l L p    Formula (I)

in which:
Fe represents the metallic ion Fe 3+ or Fe 2+ ;
m is 1 to 4;
k is 0 to 4;
l is 0 to 4;
p is 1 to 4;
X is a ligand selected from the group consisting of OH − , Cl − , F − , I − , Br, SO 4 2− , NO 3 − , ClO 4 − , PF 6 − , BF 3 − , R 1 —(COO) n − , R 1 —(SO 3 ) n − , and R 1 —(PO 3 ) n − , in which R 1 is a hydrogen atom or an optionally substituted, linear or branched C 1 to C 12 alkyl, and n=1 to 4;
L is a di-, or tetra-carboxylate ligand selected from the group consisting of:

in which:
each t independently is an integer from 1 to 4, and
each R L3 independently is H, a halogen, OH, NH 2 , NO 2 or a C 1 to C 6 alkyl.

5. The nanoparticle as claimed in claim 4 , in which L is

and R L3 and t are as defined.

6. An isoreticular porous crystalline MOF nanoparticle comprising a three-dimensional succession of units having formula (I) below:
Fe m O k X l L p    Formula (I)

in which:
Fe represents the metallic ion Fe 3+ or Fe 2+ ;
m is 1 to 4;
k is 0 to 4;
l is 0 to 4;
p is 1 to 4;
X is a ligand selected from the group consisting of OH − , Cl − , F − , I − , Br, SO 4 2− , NO 3 − , ClO 4 − , PF 6 − , BF 3 , R 1 —(COO) n − , R 1 —(SO 3 ) n − , and R 1 —(PO 3 ) n − , in which R 1 is a hydrogen atom or an optionally substituted, linear or branched C 1 to C 12 alkyl, and n=1 to 4;
L is a di-, tri-, tetra- or hexacarboxylate ligand selected from the group consisting of:

in which:
X 1 is O or S,
each t independently is an integer from 1 to 4, and
each R L3 independently is H, a halogen, OH, NH 2 , NO 2 or a C 1 to C 6 alkyl.

7. The nanoparticle as claimed in claim 4 , in which the ligand X is selected from the group consisting of OH − , Cl − , F − , CH 3 —COO − , PF 6 − , ClO 4 − , and 18 F − .

8. The nanoparticle as claimed in claim 4 , said nanoparticle comprising pores and a surface comprising at least one molecule selected from the group consisting of a pharmaceutically active principle, a compound of cosmetic interest, a fluorescent molecule, and a marker.

9. The nanoparticle as claimed in claim 8 , said nanoparticle comprising in its pores or at its surface at least one pharmaceutically active principle, the latter being selected from the group consisting of taxotere, busulfan, azidothymidine (AZT), azidothymidine phosphate (AZTP), cidofovir, gemcitabine, and tamoxifen; or at least one fluorescent molecule selected from the group consisting of rhodamines, fluorescein, luciferase, pyrene and derivatives, and aminopyrrolidino-7-nitrobenzofurazan.

10. The nanoparticle as claimed in claim 4 , said nanoparticle comprising pores and a surface wherein at least one pharmaceutically active principle has a capacity with a loading capacity of from 1% to 200% by weight of dry solid.

11. The nanoparticle as claimed in claim 8 , wherein said at least one compound of cosmetic interest is selected from the group consisting of benzophenone, visnadine, and salicylic acid.

12. The nanoparticle as claimed in claim 8 , wherein said at least one marker is selected from the group consisting of a medical imaging marker, a contrast agent, a tracer, a radioactive marker, a fluorescent marker, and a phosphorescent marker.

13. The nanoparticle as claimed in claim 12 , in which the marker is selected from the group consisting of a fluorescent compound, an iron oxide, a gadolinium complex, and gadolinium ions directly present in the structure.

14. The nanoparticle as claimed in claim 4 , further comprising on its surface at least one organic surface agent selected from the group consisting of an oligosaccharide, a polysaccharide, a glycosaminoglycan, a polymer, a surfactant, vitamins, coenzymes, antibodies or antibody fragments, amino acids, and peptides.

15. The nanoparticle as claimed in claim 14 , in which the organic surface agent is selected from the group consisting of an oligosaccharide, a polysaccharide, chitosan, dextran, hyaluronic acid, heparin, fucoidan, alginate, pectin, amylose, cyclodextrins, starch, cellulose, xylan, polyethylene glycol (PEG), pluronic, polyvinyl alcohol, polyethyleneimine, and a targeting molecule selected from the group consisting of biotin, folic acid, lipoic acid, ascorbic acid, an antibody or antibody fragment, a peptide, a protein.

16. The nanoparticle as claimed in claim 4 , wherein L is 3,5,3′,5′-azobenzenetetracarboxylate.

17. The nanoparticle as claimed in claim 4 , wherein the nanoparticle has a particle diameter of less than 1000 nm, less than 500 nm, less than 250 nm, or less than 100 nm.

18. A marker for use in medical imaging, comprising a nanoparticle as claimed in claim 4 .

19. A medicament comprising a nanoparticle as claimed in claim 4 , wherein the nanoparticl

Assignees

• Centre National De La Rech Scientifique—Cnrs
• Université De Versailles—Saint-Quentin-En-Yvelines

Inventors

• Horcajada-Cortes Patricia
• Ferey Gérard
• Serre Christian
• Gref Ruxandra
• Couvreur Patrick

Classifications

• C07F15/025 Primary

  without a metal-carbon linkage · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title