Dendronized metallic oxide nanoparticles, a process for preparing the same and their uses

Patent metadata

Field	Value
Publication number	US-10624976-B2
Application number	US-201515300939-A
Country	US
Kind code	B2
Filing date	Apr 1, 2015
Priority date	Apr 1, 2014
Publication date	Apr 21, 2020
Grant date	Apr 21, 2020

Abstract

Dendronized metallic oxide nanoparticles, a process for preparing the same and their uses.

First claim

The invention claimed is:

1. A functionalized metallic oxide nanoparticle comprising:
a metallic oxide nanoparticle and at least two compounds selected from the following compounds:

said compounds being iono-covalently bound to said metallic oxide nanoparticle via the PO 3 H 2 groups
these compounds can be functionalized by:
a ligand targeting tumor cells, abnormal cells in respect to their metabolic state or their activation state, or elements constituting an extracellular matrix,
a radioelement chelant;
a specific molecule recognition agent, being able to form a complex with said specific molecule, optionally linked to another dendrimer,
said metallic oxide nanoparticle being:
a homogenous metallic oxide nanoparticle selected from the group consisting in:
a metallic oxide of the following formula (II):
M x O y   (II)

wherein:
M is Fe,
x and y are positive integers such as y=(x·v)/2, wherein v is the average oxidation state of M in M x O y ,
a metallic oxide of the following formula (III):
Fe 3-y M′ y O 4   (III)

wherein M′ is a metal selected from the group constituted of Zn, Co, Ni and Mg, y being such as 0<y≤1,
or
a core-shell metallic oxide nanoparticule,
said core being selected from the group constituted of:
a metallic oxide of the following formula (II):
M x O y   (II)

wherein:
M is Fe,
x and y are positive integers such as y=(x·v)/2, wherein v is the average oxidation state of M in M x O y ,
a metallic oxide of the following formula (III):
Fe 3-y M′ y O 4   (III)

wherein M′ is a metal selected from the group constituted of Zn, Co, Ni and Mg, y being such as 0<y≤1, said shell being selected from the group constituted of:
a metallic oxide of the following formula (II):
M x O y   (II)

wherein:
M is Fe,
x and y are positive integers such as y=(x·v)/2, wherein v is the average oxidation state of M in M x O y ,
a metallic oxide of the following formula (III):
Fe 3-y M′ y O 4   (III)

wherein M′ is a metal selected from the group constituted of Zn, Co, Ni and Mg, y being such as 0<y≤1,
Au,
provided that:
said core and said shell are not the same metallic oxide,

said metallic oxide nanoparticle:
being a magnetic resonance imaging contrast agent, and
having a sufficient heating power for a magnetic hyperthermia treatment,
the functionalized metallic oxide nanoparticle being a dendronized nanoparticle operative as both a T2 MRI contrast agent and an agent for hyperthermia therapy.

2. The functionalized metallic oxide nanoparticle according to claim 1 , said nanoparticle having
a r 2 relaxivity value above 60 s −1 mM −1 , and a relaxivity ratio such that the r 2 /r 1 ratio is above 6,
said r 1 and r 2 values being measured with a nanoparticle having a mean hydrodynamic size of about 15 nm, and under a magnetic field of 1.41 T at 37° C., and
a specific absorption rate above 80 W/g, said rate being measured at a concentration of iron and/or magnetic metallic atom in said nanoparticle of 0.01 mol/L, at a field frequency of 700 kHz with a field amplitude of 27 mT and at 37° C.

3. The functionalized metallic oxide nanoparticle according to claim 2 , comprising an iron oxide.

4. The functionalized metallic oxide nanoparticle according to claim 1 , said nanoparticle having a r 1 relaxivity value comprised from 4 to 5 s −1 mM −1 , and a r 1 relaxivity ratio such that the r 2 /r 1 ratio is comprised from 4 to 5, r 1 and r 2 values being measured with a nanoparticle having a mean hydrodynamic size of about 15 nm, under a magnetic field of 1.41 T at 37° C.

5. The functionalized metallic oxide nanoparticle according to claim 1 , the largest dimension of which being comprised from 5 to 30 nm.

6. The functionalized metallic oxide nanoparticle according to claim 1 , said nanoparticle being:
cubic, rodshaped, octopod-shaped or nanoplatelet-shaped, and/or
a core-shell metallic oxide nanoparticule.

7. A chain of functionalized metallic oxide nanoparticles according to claim 1 , said chain being linear.

8. A method for medical imaging comprising the use of a functionalized metallic oxide nanoparticle according to claim 1 .

9. A method for the treatment of tumors or other pathological tissues comprising the use of a functionalized metallic oxide nanoparticle according to claim 1 , as a hyperthermia and/or radiosensitizing agent.

10. A pharmaceutical or diagnostic composition comprising functionalized metallic oxide nanoparticles according to claim 1 , as active agents and a pharmaceutically acceptable vehicle.

Assignees

• Centre Nat Rech Scient
• Univ Strasbourg
• Hospices Civils Lyon
• Univ Claude Bernard Lyon
• Univesite De Strasbourg

Inventors

• Begin-Colin Sylvie
• Felder-Flesch Delphine
• Billotey Claire
• Pichon Benoit

Classifications

• A61K49/1842

  the small organic molecule being a phosphate or a phosphonate, not being a phospholipid · CPC title

• C01P2004/38

  cube-like · CPC title

• C01P2004/32

  Spheres · CPC title

• C01G45/02

  Oxides · CPC title

• C01P2004/84

  one phase coated with the other · CPC title