PRODUCTION OF NANOSCALE POWDERS OF EMBEDDED NANOPARTICLES

Abstract

The invention provides a liquid-dispersible powder comprising nanoscale grains of matrix embedded with one or more isolated nanoparticles and a composition for the magnetic nanoparticle hyperthermia (MNH) treatment of tumours comprising nanoscale grains of matrix material containing one or more isolated nanoparticles. The invention also provides a method of production of a liquid-dispersible powder described herein, the method comprising the steps of providing nanoparticles prepared under ultra-high vacuum (UHV) gas phase conditions; co-depositing the nanoparticles within a matrix material under UHV gas phase conditions; and grinding the film to a fine powder comprising grains of groups of matrix material isolated nanoparticles. The invention also provides a method of reducing the agglomeration of nanoparticles in liquid, the method comprising isolating nanoparticles in nanoscale grains of matrix material, and the use of a liquid-dispersible powder comprising nanoscale grains of matrix material containing one or more isolated nanoparticles in the manufacture of a medicament for the MNH treatment of tumours.

Claims

1. A liquid-dispersible powder comprising nanoscale grains of a matrix material composed of one or more biocompatible oxides, in which the matrix material contains a plurality of isolated nanoparticles, wherein each nanoparticle comprises a magnetic core selected from one or more of Fe or an alloy of Fe/Co.

2. A composition for the magnetic nanoparticle hyperthermia (MNH) treatment of tumours comprising nanoscale grains of a matrix material containing one or more isolated nanoparticles.

3. A composition according to claim 2, wherein the nanoscale grains are provided in the form of a liquid dispersible powder.

4. A liquid-dispersible powder according to claim 1, wherein the nanoparticles are around 15 nm in size.

5. A liquid-dispersible powder according to claim 1, wherein each magnetic nanoparticle comprises a magnetic core selected from one or more of Fe or an alloy of Fe/Co encased in a biocompatible shell.

6. A liquid-dispersible powder according to claim 5, in which the biocompatible shell comprises one or more of: Fe oxide, gold, or silver, or any combination thereof.

7. A method of production of a liquid-dispersible powder according to claim 1, the method comprising the steps of: a. providing nanoparticles prepared under ultra-high vacuum (UHV) gas phase conditions, wherein each magnetic nanoparticle comprises a magnetic core selected from one of more of Fe or an alloy of Fe/Co; b. co-depositing a plurality of nanoparticles within a matrix material composed of one or more biocompatible oxides under UHV gas phase conditions; c. grinding the film to a fine powder comprising grains of groups of matrix isolated nanoparticles.

8. A method according to claim 7, wherein the grinding step comprises ball milling.

9. A method of reducing the agglomeration of nanoparticles in liquid, the method comprising isolating a plurality of nanoparticles in nanoscale grains of a matrix material composed of one or more biocompatible oxides.

10. A method according to claim 9, wherein the nanoparticles are isolated in the matrix material under UHV gas phase conditions.

11. A liquid-dispersible powder according to claim 1 for use in the magnetic nanoparticle hyperthermia (MNH) treatment of tumours.

12. A method according to claim 7, wherein the nanoparticles are around 15 nm in size.

13. A method according to claim 7, wherein each magnetic nanoparticle comprises a magnetic core selected from one of more of Fe or an alloy of Fe/Co encased in a biocompatible shell.

Description

DESCRIPTION OF THE DRAWINGS

[0028] Embodiments of the present invention will now be described by way of example only and with reference to the following figures:

[0029] FIG. 1 (a) shows a thin film of matrix with embedded nanoparticles prior to milling, in accordance with a first embodiment of the present invention; and

[0030] FIG. 1(b) shows nanoscale grains of matrix with embedded nanoparticles after milling, in accordance with the embodiment of FIG. 1.

SPECIFIC DESCRIPTION

[0031] Magnetic nanoparticles with an iron (Fe) core surrounded by a biocompatible shell, for example iron oxide (FeO) which is otherwise referred to as Fe@FeO nanoparticles, were produced using ultra-high vacuum (UHV) gas-phase methods. It is however to be understood that the present invention is not limited to magnetic nanoparticles comprising an iron core. The nanoparticles may comprise other magnetic cores, such as for example alloy cores such as for example iron/cobalt alloy cores. It is also to be understood that the biocompatible shell is not limited to being composed of iron oxide. The biocompatible shell may be composed of one or more of: Fe oxide, gold or silver particles, or any combination thereof. The nanoparticles may for example comprise one or more of an iron core surrounded with iron oxide (Fe@FeO), an iron core surrounded with gold (Fe@Au), or an iron core surrounded with silver (Fe@Ag), or any combination thereof. The use of UHV gas-phase methods facilitates the production of magnetic nanoparticles having a relatively narrow size distribution of around 10 nm in size, whilst minimising nanoparticle agglomeration. Uncontrolled particle agglomeration would adversely affect the desirable properties of the nanoparticles.

[0032] The nanoparticles, for example Fe@FeO nanoparticles, are then co-deposited within a matrix under UHV conditions to produce a thin film with embedded isolated magnetic nanoparticles. The matrix material may be any material capable of sputter coating. Suitable oxides include, but are not limited to, one or more of: Al.sub.2O.sub.3 or alumina. Any suitable method of sputter coating of the nanoparticles with the matrix material may be used. For example, the oxide coatings may for example be provided using a pulsed or RF power supply at approximately 100 W and a gas pressure of approximately 0.1 mbar. It is however to be understood that the method of depositing nanoparticles within the matrix material is not to be limited to these process parameters.

[0033] FIG. 1(a) shows such a thin film matrix 10 with embedded nanoparticles 20 isolated within the film 10. As can be seen from FIG. 1, there is no agglomeration of the nanoparticles 20 within the film 10 and each nanoparticle 20 is spatially isolated from neighbouring nanoparticles 20.

[0034] In order to use the magnetic nanoparticles in medical applications, the nanoparticles must be liquid-dispersible, for example water-dispersible. Therefore, the thin film was subjected to grinding by a ball mill to produce a fine powder of nanoscale grains 30 of matrix containing small groups of embedded magnetic nanoparticles 20. FIG. 1(b) shows the film 10 of FIG. 1 after the milling process. Nanoscale grains 30 of matrix 10 are shown, each approximately 100 nm in size, each grain 30 having a group of embedded magnetic nanoparticles 20 clearly spatially isolated from one another.

[0035] It should be noted that the nanoscale grains 30 of matrix 10 isolated nanoparticles 20 as shown in FIG. 1(b) which are each approximately 100 nm in size are still small enough for use in medical applications such as the magnetic nanoparticle hyperthermia (MNH) treatment of tumours or bacterial infections. The size of each nanoscale grain 30 is still at least 100 times smaller than the finest capillaries in the human body.

[0036] In order to use the fine powder of nanoscale grains 30 in medical applications, the fine powder must be dispersed in liquid. The nanoscale dimensions of the grains 30 facilitates efficient dispersal of the grains 30 in liquid, such as but not limited to water. The fine powder may be added to water to provide a liquid composition comprising nanoscale grains of matrix embedded with a plurality of isolated nanoparticles which can be used for medical applications such as, but not restricted to MNH treatment of cancer tumours.

[0037] This embodiment of the present invention demonstrates how a suspension of magnetic nanoparticles can be produced for medical applications whilst avoiding the typical problems of agglomeration. It should be noted that due to the arrangement of embedded nanomagnetic particles within the thin matrix of each grain 30, even if some agglomeration of grains 30 within a liquid is experienced, the magnetic nanoparticles will remain spatially isolated from one another, thereby retaining their desirable properties.

[0038] Finally, it is to be appreciated that the milling process itself will result in some modification of the individual nanoparticles. For example, the strain induced by the milling process would alter the magnetic anisotropy of the nanoparticles. Therefore, the milling process itself can be used as an additional way of controlling the characteristics of the nanoparticles and the performance of the final fine powder.

[0039] Although the example refers to the use of Fe @FeO nanoparticles it is to be understood that the present invention is not limited to magnetic nanoparticles comprising an Fe core coated in a biocompatible shell comprising FeO. The magnetic nanoparticles may comprise a core selected from one or more of Fe or an alloy of Fe/Co. The biocompatible shell may comprise one or more of FeO, gold, or silver, or any combination thereof.