Phase-change nanoparticle

• US 9,872,902 B2
• Filed: 04/04/2017
• Issued: 01/23/2018
• 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 JOSEPH
• Application Number:
  US15/478,849
• Publication Number:
  US 20170209580A1
• Time in Patent Office: 294 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 for use with a subject suffering from cancer, a body of the subject containing cancerous cells and non-cancerous cells, and for use with a heating device configured to heat at least a portion of the subject'"'"'s body, the apparatus comprising:

a nanoparticle comprising;

an inner core 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.;

an outer layer disposed around the inner core, the outer layer comprising;

a plurality of nano-spheres of at least one metal; and

a plurality of molecules of a substance that binds preferentially with cancerous cells relative to non-cancerous cells,

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

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 nanoparticle is configured to become elongated in response to hydrostatic pressure within the subject'"'"'s body.

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

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. The apparatus according to claim 1, 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.

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

12. The apparatus according to claim 1, wherein the nanoparticle further comprises a plurality of polymer chains disposed between the inner core and the outer layer, the outer layer being bound to the inner core via the polymer chains.

13. The apparatus according to claim 1, wherein the nanoparticle further comprises a plurality of polymer chains disposed around the outer layer.

14. The apparatus according to claim 13, wherein the polymer chains are configured to at least partially mask at least the outer layer from phagocytic cells of a mononuclear phagocyte system of the subject.

15. 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.

16. The apparatus according to claim 15, 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.

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

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

19. The apparatus according to claim 1, wherein the inner core has a volume of 50,000-270,000 nm³.

20. The apparatus according to claim 1, wherein the phase-change material comprises an organic phase-change material.

21. A method comprising:

synthesizing a nanoparticle to have a volume of at least 65,000 nm3, and to be 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,

the synthesizing being performed by;

providing an inner core 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.,

binding an outer layer to the inner core, the outer layer including;

a plurality of nano-spheres of at least one metal, and

a plurality of molecules of a substance that binds preferentially with cancerous cells relative to non-cancerous cells.

22. The method according to claim 21, wherein synthesizing the nanoparticle comprises synthesizing the nanoparticle to be elongatable in response to hydrostatic pressure.

23. The method according to claim 21, wherein synthesizing the nanoparticle comprises synthesizing the nanoparticle to be elongatable in response to osmotic pressure.

24. The method according to claim 21, wherein binding the outer layer to the inner core comprises binding an outer layer to the inner core, the outer layer including a plurality of gold nano-spheres.

25. The method according to claim 21, wherein binding the outer layer to the inner core comprises binding the outer layer to the inner core via a plurality of polymer chains.

26. The method according to claim 21, wherein synthesizing the nanoparticle comprises binding a plurality of polymer chains to the outer layer, such that the polymer chains are disposed around the outer layer.

27. The method according to claim 21, wherein binding the outer layer to the inner core comprises binding an outer layer to the inner core, each of the nano-spheres of the outer layer having a diameter that is between 1 nm and 10 nm.

28. The method according to claim 21, wherein binding the outer layer to the inner core comprises binding an outer layer to the inner core, each of the nano-spheres of the outer layer being separated from all others of the nano-spheres of the outer layer by a minimum separation of between 0.3 nm and 2 nm.

29. The method according to claim 21, wherein providing the inner core that includes the phase-change material comprises providing an inner core having a volume of 50,000-270,000 nm³.

30. The method according to claim 21, wherein providing the inner core that includes the phase-change material comprises providing an inner core that includes an organic phase-change material.