Nanoparticle-sized magnetic absorption enhancers having three-dimensional geometries adapted for improved diagnostics and hyperthermic treatment

• US 9,844,679 B2
• Filed: 10/02/2013
• Issued: 12/19/2017
• Est. Priority Date: 10/31/2009
• Status: Active Grant

• Current Assignee: Qteris, Inc.
• Original Assignee: Qteris, Inc.
• Inventors: Nayfach-Battilana, Joseph N.
• Primary Examiner(s): Stoklosa, Joseph
• Assistant Examiner(s): Avigan, Adam
• Application Number:
  US14/044,251
• Publication Number:
  US 20140172049A1
• Time in Patent Office: 1,539 Days
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 47/6835 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
• CPC Class Codes: A61K 49/183 having a (super)(para)magnetic core coated or functionalised with an inorganic material or being composed of an inorganic material entrapping the MRI-active nucleus, e.g. silica core doped with a MRI-active nucleus
• CPC Class Codes: A61K 49/1854 the organic macromolecular compound being obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly(meth)acrylate, polyacrylamide, polyvinylpyrrolidone, polyvinylalcohol
• CPC Class Codes: A61K 49/1857 the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
• CPC Class Codes: A61K 49/186 the organic macromolecular compound being polyethyleneglycol [PEG]
• CPC Class Codes: A61K 49/1863 the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
• 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 31/04 Antibacterial agents

Abstract

Nanoparticle-sized magnetic absorption enhancers (MAEs) exhibiting a controlled response to a magnetic field, including a controlled mechanical response and an inductive thermal response. The MAEs have a magnetic material that exhibits inductive thermal response to the magnetic field and is embedded in a coating, such that the MAE conforms to a particular shape, e.g., hemisphere, dome or shell, chosen to produce the controlled mechanical response. A targeting moiety for specifically binding the MAE to a pathogen target is also provided. The MAEs can be bound by a flexible linker to promote the desired mechanical response, which includes interactions between MAEs that are not bound to any pathogen target for the purpose of forming spheres, spherical shells, or generally spherical dimers to contain the thermal energy produced and to thus reduce collateral healthy tissue damage during hyperthermic treatment.

Claims

1. A method for inducing transient hyperthermia in a pathogen target, said method comprising the following steps:

a) generating a magnetic field;

b) producing a nanoparticle-sized magnetic absorption enhancer exhibiting a controlled response to said magnetic field by;

i) providing a magnetic material having an inductive thermal response to said magnetic field;

ii) embedding said magnetic material in a coating that conforms to a predetermined shape complementary to the shape of at least one other magnetic absorption enhancer, thereby enabling a controlled mechanical response of said magnetic absorption enhancer to said magnetic field; and

iii) providing a targeting moiety for specific binding of said magnetic absorption enhancer to a pathogen target;

c) delivering said magnetic absorption enhancer to a region comprising said pathogen target for specific binding to said pathogen target;

wherein said controlled response comprises said inductive thermal response for applying a high temperature transient to said pathogen target and said controlled mechanical response comprises an interaction between said magnetic absorption enhancer and said at least one other magnetic absorption enhancer for limiting collateral damage to healthy tissue.

2. The method of claim 1, wherein said magnetic field comprises an alternating magnetic field and a static magnetic field.

3. The method of claim 1, wherein said magnetic field is a static magnetic field and said magnetic material exhibits a magnetic dipole-dipole coupling response.

4. The method of claim 3, wherein said magnetic dipole-dipole coupling response affects said controlled mechanical response, whereby said controlled mechanical response further comprises a change in said predetermined shape.

5. The method of claim 4, wherein said change comprises a bending of said magnetic absorption enhancer.

6. The method of claim 5, wherein said predetermined shape comprises a shell, and said bending contains said inductive thermal response.

7. The method of claim 1, wherein a flexible linker is provided for binding said magnetic absorption enhancer to said at least one other magnetic absorption enhancer.

8. The method of claim 7, wherein said flexible linker is attached to said coating.

9. The method of claim 7, wherein said predetermined shape is selected from the group consisting of hemisphere, dome and shell.

10. The method of claim 9, wherein said predetermined shape is chosen to be a shell, and said controlled mechanical response comprises a pinching of said shell for containing said inductive thermal response.

11. The method of claim 7, wherein said shape of said at least one other magnetic absorption enhancer is selected from the group consisting of hemisphere, dome and shell.

12. The method of claim 11, wherein said interaction of said magnetic absorption enhancer and said at least one other magnetic absorption enhancer forms a sphere for containing said inductive thermal response.

13. The method of claim 11, wherein said interaction of said magnetic absorption enhancer and said at least one other magnetic absorption enhancer forms a spherical shell for containing said inductive thermal response.

14. The method of claim 11, wherein said interaction of said magnetic absorption enhancer and said at least one other magnetic absorption enhancer forms a generally spherical dimer for containing said inductive thermal response.

15. The method of claim 1, wherein said predetermined shape is selected from the group consisting of a hemisphere, a dome and a shell.

16. The method of claim 15, wherein said predetermined shape is a hemisphere and said targeting moiety is attached to the face of said hemisphere.

17. The method of claim 15, wherein said predetermined shape is a dome and said targeting moiety is attached to the inner portion of said dome.

18. The method of claim 15, wherein said predetermined shape is a shell and said targeting moiety is attached to an inner face of said shell.