Phase-change nanoparticle

• US 10,172,939 B2
• Filed: 12/22/2017
• Issued: 01/08/2019
• Est. Priority Date: 11/25/2014
• Status: Active Grant

• Current Assignee: New Phase, Ltd.
• Original Assignee: New Phase, Ltd.
• Inventors: Hof, Raphael, Khandadash, Raz, Fremder, Ella
• Primary Examiner(s): Stoklosa, Joseph
• Assistant Examiner(s): Avigan, Adam
• Application Number:
  US15/852,293
• Publication Number:
  US 20180117154A1
• Time in Patent Office: 382 Days
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• 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: A61P 35/00 Antineoplastic agents

Abstract

Apparatus and methods are described for use with a subject suffering from cancer. A nanoparticle (22) includes an inner core (30) that comprises a phase-change material that is configured to absorb latent heat of fusion by undergoing a phase change. An outer layer (32) disposed around the inner core includes a plurality of nano-spheres (34) of at least one metal, and a plurality of molecules (38) of a substance that binds preferentially with cancerous cells relative to non-cancerous cells. The nanoparticle has a volume of at least 65,000 nm³ and is elongatable into an ellipsoid, such that, when the nanoparticle is maximally elongated, each of the semi-axes defined by the ellipsoid is greater than 5 nm, and at least two of the semi axes of the ellipsoid are less than 30 nm. Other applications are also described.

Claims

1. Apparatus comprising:

a nanoparticle configured to be administered to a body of a subject, the nanoparticle comprising;

a phase-change-material layer that comprises a phase-change material that is configured to absorb latent heat of fusion by undergoing a phase change selected from the group consisting of;

solid to liquid, and gel to liquid, the phase-change occurring at a phase-change temperature of between 42°

C. and 80°

C.; and

an nano-sphere layer disposed around the phase-change-material layer,

the nano-sphere layer comprising a plurality of nano-spheres of at least one metal,

the nanoparticle having a volume of at least 65,000 nm³, and

the nanoparticle being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated;

each of the semi-axes defined by the ellipsoid is greater than 5 nm, and

at least two of the semi axes of the ellipsoid are less than 30 nm.

2. The apparatus according to claim 1, wherein the nano-sphere layer of the nanoparticle further comprises a plurality of molecules of a substance that binds preferentially with cancerous cells relative to non-cancerous cells.

3. The apparatus according to claim 1, wherein the nanoparticle is configured to become elongated in response to hydrostatic pressure within the subject'"'"'s body.

4. The apparatus according to claim 1, wherein the nanoparticle is configured to become elongated in response to osmotic pressure within the subject'"'"'s body.

5. The apparatus according to claim 1, wherein the nanoparticle is configured to be blocked from passing through a blood brain barrier of the subject, by being elongatable into an ellipsoid, such that even when the nanoparticle is maximally elongated, each of the semi-axes defined by the ellipsoid is greater than 5 nm.

6. The apparatus according to claim 1, wherein the nanoparticle is configured to be able to pass through a liver of the subject, by being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

7. The apparatus according to claim 1, wherein the nanoparticle is configured to be able to pass through glands of the subject, by being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

8. The apparatus according to claim 1, wherein the nanoparticle is configured to be able to pass through a mononuclear phagocyte system of the subject, by being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

9. The apparatus according to claim 1, wherein the nanoparticle is configured to be able to pass through a spleen of the subject, by being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

10. The apparatus according to claim 1, wherein the phase-change material is configured to prevent the nanoparticle from being heated to a temperature that is greater than the phase change temperature, by absorbing latent heat of fusion.

11. The apparatus according to claim 1, wherein the nanoparticle is configured to be used with a heating device that is configured to heat at least a portion of the subject'"'"'s body, and wherein the nano-spheres of the at least one metal are configured to cause the nanoparticle to preferentially absorb energy from the heating device relative to tissue of the subject.

12. The apparatus according to claim 1, wherein the nano-spheres of the at least one metal comprise gold nano-spheres.

13. The apparatus according to claim 1, wherein the nanoparticle further comprises a plurality of polymer chains disposed between the phase-change-material layer and the nano-sphere layer, the nano-sphere layer being bound to the phase-change-material layer via the polymer chains.

14. The apparatus according to claim 1, wherein each of the nano-spheres has a diameter that is between 1 nm and 10 nm.

15. The apparatus according to claim 1, wherein each of the nano-spheres is separated from all others of the nano-spheres of the nano-sphere layer by a minimum separation of between 0.3 nm and 2 nm.

16. The apparatus according to claim 1, wherein the phase-change-material layer has a volume of 50,000-270,000 nm³.

17. The apparatus according to claim 1, wherein the nanoparticle further comprises a plurality of polymer chains disposed around the nano-sphere layer.

18. The apparatus according to claim 17, wherein the polymer chains are configured to at least partially mask at least the nano-sphere layer from phagocytic cells of a mononuclear phagocyte system of the subject.

19. The apparatus according to claim 1, wherein the nanoparticles are configured to be used with an inductive radiofrequency heating device, and wherein the nano-spheres are configured to be heated by the inductive radiofrequency heating device.

20. The apparatus according to claim 19, wherein the nanoparticles are configured to be used with an inductive radiofrequency heating device that transmits RF energy at a given frequency, and wherein the nano-spheres have a resonant frequency that matches the given frequency.

21. A method for use with a body of a subject, the method comprising:

administering at least one nanoparticle to the subject'"'"'s body,

the nanoparticle including;

a phase-change-material layer that includes a phase-change material that is configured to absorb latent heat of fusion, by undergoing a phase change selected from the group consisting of;

solid to liquid, and gel to liquid, the phase-change occurring at a phase-change temperature of between 42°

C. and 80°

C., and

a nano-sphere layer disposed around the inner core, the nano-sphere layer including a plurality of nano-spheres of at least one metal, each of the nanoparticles having a volume of at least 65,000 nm3, and

the nanoparticle being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated;

each of the semi-axes defined by the ellipsoid is greater than 5 nm, and

at least two of the semi axes of the ellipsoid are less than 30 nm; and

subsequent to administering the nanoparticle to the subject, heating at least a portion of the subject'"'"'s body to the phase-change temperature of the phase-change material, using a heating device.

22. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises administering the nanoparticle to the subject'"'"'s body, the nano-sphere layer of the nanoparticle further including a plurality of molecules of a substance that binds preferentially with cancerous cells relative to non-cancerous cells.

23. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises administering the nanoparticle to the subject'"'"'s body, the nanoparticle being configured to become elongated in response to hydrostatic pressure within the subject'"'"'s body.

24. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises administering the nanoparticle to the subject'"'"'s body, the nanoparticle being configured to become elongated in response to osmotic pressure within the subject'"'"'s body.

25. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises preventing the nanoparticle from passing through a blood brain barrier of the subject'"'"'s body, due to the nanoparticle being elongatable into an ellipsoid, such that even when the nanoparticle is maximally elongated, each of the semi-axes defined by the ellipsoid is greater than 5 nm.

26. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises facilitating the nanoparticle passing through glands of the subject, due to the nanoparticle being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

27. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises facilitating the nanoparticle passing through a mononuclear phagocyte system of the subject, due to the nanoparticle being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

28. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises facilitating the nanoparticle passing through a liver of the subject, due to the nanoparticle being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

29. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises facilitating the nanoparticle passing through a spleen of the subject, due to the nanoparticle being elongatable into an ellipsoid, such that when the nanoparticle is maximally elongated at least two of the semi axes of the ellipsoid are less than 30 nm.

30. The method according to claim 21, wherein administering the nanoparticle to the subject'"'"'s body comprises administering the nanoparticle to the subject'"'"'s body, the nano-spheres of the metal of the nano-sphere layer of the nanoparticles comprising gold nano-spheres.