System generating a constraint field, and medical device implementing the same

• US 10,449,160 B2
• Filed: 07/11/2014
• Issued: 10/22/2019
• Est. Priority Date: 07/12/2013
• Status: Active Grant

• Current Assignee: Cell Constraint & Cancer Co.
• Original Assignee: Cell Constraint & Cancer Co.
• Inventors: Brossel, Remy
• Primary Examiner(s): Wilson, Kaylee R
• Application Number:
  US14/904,580
• Publication Number:
  US 20160143859A1
• Time in Patent Office: 1,929 Days
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61N 1/406 using implantable thermoseeds or injected particles for localized hyperthermia preparations of seeds and particles A61K41/0052
• CPC Class Codes: A61N 2/004 specially adapted for a specific therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Disclosed is a system including (1) an injection device including injectable magnetizable nanoparticles and a component for injecting the same, and (2) a unit for applying a constraint physically and/or mechanically to a tumor associated to an neoangiogenic network where, after having been injected, the particles are retained. Also disclosed is a method for treating tumors, especially tumors associated with a neoangiogenic network, including the steps of: injecting a composition including magnetizable nanoparticles; optionally performing imaging using an imaging device to detect a concentration of nanoparticles retained in the neoangiogenic network; and applying a contact-free constraint onto a tumor in vivo, by a gradient of magnetic field and the application being directed to the tumor region.

Claims

1. A medical system comprising:

injectable magnetizable nanoparticles having a mean diameter ranging from 10 to 800 nm;

a device for injecting the nanoparticles; and

a generator that releases a gradient of magnetic field for applying a mechanical constraint comprising contact-free compression, actuated by the injected nanoparticles, onto tumor cells of a tumor having a neoangiogenic network where, after having been injected, at least 25-60% of the injected nanoparticles are retained in the tumor neoangiogenic network to apply the contact-free compression onto the tumor cells,

wherein the medical system is free of being a cell construct, free of being an implant, free of any pharmaceutical agent for treating the tumor, free of the nanoparticles being drug carriers, and free of the nanoparticles being imaging agents.

2. The medical system according to claim 1, wherein the nanoparticles are composed of iron oxide.

3. The medical system according to claim 2, wherein the nanoparticles comprise magnetite (Fe3O4), maghemite ([gamma]-Fe2O3), ferumoxides or mixtures thereof.

4. The medical system according to claim 2, wherein said nanoparticles are coated with a non-pharmaceutical composition.

5. The medical system according to claim 2, wherein said nanoparticles have a mean diameter ranging from 20 to 300 nm.

6. The medical system according to claim 2, wherein the nanoparticles are suspended in a colloidal or non-colloidal vehicle.

7. The medical system according to claim 1, wherein said nanoparticles are coated with a non-pharmaceutical composition.

8. The medical system according to claim 7, wherein said nanoparticles have a mean diameter ranging from 20 to 300 nm.

9. The medical system according to claim 7, wherein the nanoparticles are suspended in a colloidal or non-colloidal vehicle.

10. The medical system according to claim 1, wherein said nanoparticles have a mean diameter ranging from 20 to 300 nm.

11. The medical system according to claim 10, wherein the nanoparticles are suspended in a colloidal or non-colloidal vehicle.

12. The medical system according to claim 1, wherein the nanoparticles are suspended in a colloidal or non-colloidal vehicle.

13. The medical system according to claim 1, wherein the generator releases the gradient as a gradient of constant or variant magnetic field.

14. A method for treating a tumor region, said tumor region comprising a tumor, the extracellular matrix and/or the stroma and the neoangiogenic network surrounding the tumor, said method comprising the steps of:

injecting a composition containing an amount of nanoparticles, the nanoparticles having a mean diameter ranging from 10 to 800 nm; and

using a generator for releasing a gradient of magnetic field to apply a contact-free mechanical constraint comprising contact-free compression, actuated by the injected nanoparticles, onto the tumor in vivo, wherein the nanoparticles are free of any pharmaceutical agent for treating the tumor by applying the contact-free compression onto the tumor cells.

15. The method according to claim 14, wherein the amount of injected nanoparticles ranges from 100 μ

g to 10 g.

16. The method according to claim 14, wherein at least 25-60% of the injected nanoparticles are retained in the tumor neoangiogenic network of the tumor region and the injected nanoparticles retained in the tumor neoangiogenic network apply the contact-free compression onto the tumor cells.

17. The method according to claim 14, wherein the tumor is a malignant epithelial tumor.

18. The method according to claim 14, wherein the tumor is a pancreas cancer tumor, or a breast cancer tumor.

19. A method for modifying the cancerous phenotype of cancer cells to normal cells in a tumor region, the method comprising the steps of:

injecting a composition containing nanoparticles such that the nanoparticles are retained by the neoangiogenic network of the tumor region, the nanoparticles being injectable magnetizable nanoparticles having a mean diameter ranging from 10 to 800 nm, the nanoparticles being free of any pharmaceutical agent for treating a tumor; and

using a generator for releasing a gradient of magnetic field to apply a contact-free mechanical constraint comprising contact-free compression, actuated by the injected nanoparticles retained in the tumor neoangiogenic network, onto the cancer cells.

20. The method according to claim 19, wherein the modified cancer phenotype leads to the reduction of tumor volume and/or surfaces of the tumor cells.