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

• US 8,565,892 B2
• Filed: 11/01/2010
• Issued: 10/22/2013
• 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): Dvorak, Linda
• Assistant Examiner(s): PIKE, JARED WAYNE
• Application Number:
  US12/925,904
• Publication Number:
  US 20110105825A1
• Time in Patent Office: 1,086 Days
• Field of Search: 607/96, 607/103, 600 9- 15, 436/526, 977/904
• US Class Current: 607/103
• 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) that exhibit a controlled response to a magnetic field, including a controlled mechanical response and inductive thermal response. The MAEs have a magnetic material that exhibits the inductive thermal response to the magnetic field and is embedded in a coating, such that the MAE conforms to a particular shape, e.g., a hemisphere, a dome or a shell, that is chosen to produce the desired controlled mechanical response of the entire MAE to the magnetic field. A targeting moiety for specifically binding the MAE to a pathogen target is also provided. The MAEs are preferably bound by a flexible linker to promote the desired mechanical response, which includes interactions between MAEs that are not bound to their pathogen target for the purpose of forming spheres, spherical shells, or generally spherical dimers. Such forms contain the thermal energy produced by the thermal inductive response of the magnetic material and thus reduce collateral healthy tissue damage during hyperthermic treatment. The inventing extends to appropriate apparatus and methods for diagnostics and hyperthermic treatments employing the MAEs.

Claims

1. A nanoparticle-sized magnetic absorption enhancer exhibiting a controlled response to a magnetic field, said magnetic absorption enhancer comprising:

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

b) a coating embedding said magnetic material and conforming to a predetermined shape complementary to the shape of at least one other magnetic absorption enhancer, and producing a controlled mechanical response of said magnetic absorption enhancer to said magnetic field; and

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

wherein said controlled response comprises said inductive thermal response and said controlled mechanical response comprising an interaction between said magnetic absorption enhancer and said at least one other magnetic absorption enhancer.

2. The magnetic absorption enhancer of claim 1, further comprising a flexible linker for binding said magnetic absorption enhancer to said at least one other magnetic absorption enhancer.

3. The magnetic absorption enhancer of claim 2, wherein said flexible linker is attached to said coating.

4. The magnetic absorption enhancer of claim 1, wherein said predetermined shape is selected from the group consisting of hemisphere, dome and shell.

5. The magnetic absorption enhancer of claim 4, wherein said magnetic material is distributed in a plurality of magnetic crystals embedded in said coating.

6. The magnetic absorption enhancer of claim 5, wherein each of said magnetic crystals comprises a single magnetic domain.

7. The magnetic absorption enhancer of claim 4, 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.

8. The magnetic absorption enhancer of claim 4, 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.

9. The magnetic absorption enhancer of claim 4, 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.

10. The magnetic absorption enhancer of claim 4, wherein said predetermined shape is a shell, and said controlled mechanical response comprises a pinching of said shell for containing said inductive thermal response.

11. The magnetic absorption enhancer of claim 1, wherein said controlled mechanical response comprises a joining of said magnetic absorption enhancer with said at least one other magnetic absorption enhancer.

12. The magnetic absorption enhancer of claim 1, wherein said targeting moiety is in direct contact with said magnetic material.

13. The magnetic absorption enhancer of claim 12, wherein said coating has a passage for said targeting moiety to reach said magnetic material.

14. The magnetic absorption enhancer of claim 1, wherein said predetermined shape is a hemisphere and said targeting moiety is attached to the face of said hemisphere.

15. The magnetic absorption enhancer of claim 1, wherein said predetermined shape is a shell and said targeting moiety is attached to an inner face of said shell.

16. The magnetic absorption enhancer of claim 1, wherein said predetermined shape is a dome and said targeting moiety is attached to the inner portion of said dome.

17. The magnetic absorption enhancer of claim 1, wherein said targeting moiety is attached to said magnetic absorption enhancer by a bond.

18. The magnetic absorption enhancer of claim 17, wherein said bond is selected from the croup of bonding mechanisms consisting of passive absorption, covalent coupling, hydrogen bonding, secondary, or tertiary amine linkage, amide linkage, Schiff base linkage, isourea linkage, thiourea linkage, carbamate linkage, ether linkages, thioether linkages, strept(avidin)-biotin interactions, hydrazone linkages, SPDP crosslinker coupling.

19. The magnetic absorption enhancer of claim 1, wherein said coating comprises a bioccmpatible material.

20. The apparatus of claim 19, wherein said biocompatible material is selected from the group consisting of SiO₂, dextran, gold, silver and polyethylene glycol biodegradable polymers, modified dextran coatings, cross-linked dextran coatings, polylactide/polyglycolide copolymers, poly(orthoesters), poly(anhydrides), microemulsions, liposomes, and thermally sensitive lyposomes (LTSLs, HTSLs).

21. An apparatus for inducing transient hyperthermia in a pathogen target, said apparatus comprising:

a) a means for generating a magnetic field;

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

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

ii) a coating embedding said magnetic material and conforming to a predetermined shape, thereby producing a controlled mechanical response of said magnetic absorption enhancer to said magnetic field; and

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

wherein said controlled response comprises said inductive thermal response and said controlled mechanical response comprises an interaction of said magnetic absorption enhancer with at least one other magnetic absorption enhancer to form a geometrical arrangement for containing said inductive thermal response.

22. The apparatus of claim 21, wherein said means for generating said magnetic field comprise NMR coils and said magnetic field comprises an alternating magnetic field.

23. The apparatus of claim 21, wherein said controlled mechanical response comprises a change in said predetermined shape.

24. The apparatus of claim 23, wherein said change comprises a bending of said magnetic absorption enhancer when said magnetic field is being generated.