JP2019094337A - Protein and antibody - Google Patents

Abstract

To provide methods for treating cancer and an apparatus therefor, particularly to provide cancer treatment methods for the treatment by irradiating an affected part with electromagnetic waves, and magnetic particles and an apparatus used therefor.SOLUTION: Provided is a method for treating cancer, in which magnetic particles bound to an antibody against cancer cells are noninvasively or minimally introduced into patient's body to bind to the cancer cells, and from the outside, an electromagnetic wave is radiated or a magnetic field is applied, so as to inductively heat and kill the magnetic particles bound to the cancer cells. The method further comprises magnetically introducing magnetic particles into the vicinity of the cancer cells after the magnetic particles into the patient's body, and the magnetic particles are derived from an organism, preferably.SELECTED DRAWING: None

Description

  The present invention relates to a cancer treatment method and apparatus therefor, and more particularly to a cancer treatment method for treating an affected area by irradiating an electromagnetic wave, and magnetic particles and apparatus used therefor.

  Heretofore, treatment methods for irradiating cancer with energy rays have been practiced using a linear accelerator. The problems that arise when performing this radiation treatment are the absorbed dose in the abnormal tissue to be treated and the adverse effect on normal tissue. In order to reliably treat abnormal tissue, it is necessary to ensure that a lethal dose is applied to the abnormal tissue. However, if irradiation is performed simply, it will have a side effect on surrounding normal tissues. Therefore, measures have been taken to reduce radiation damage to normal tissue by rotational irradiation, multi-field irradiation, or radiotherapy (conformal irradiation) that adjusts multi-field irradiation by adjusting the collimator shape according to the shape of the affected area. .

  However, even if any device as described above is performed, deviation of reference coordinates between the diagnostic apparatus such as an X-ray CT apparatus or an MRI apparatus used for diagnosis and position determination of the affected area and the treatment irradiation apparatus The irradiation field positioning accuracy of the radiation treatment apparatus can not be secured because of the problem of the irradiation shadow based on the size, etc., and sufficient treatment effect has not been achieved. One solution to this is by mechanically fixing the positioning frame to surround the treatment site, referencing this frame and dividing one source into multiple small dose sources, It is to minimize the irradiation penumbra. A gamma knife is known as a typical example of such an approach.

  However, the gamma knife can not be applied to a region where the frame can not be attached, such as the chest and abdomen, and even if accurate reference coordinates can be set, it can not cope with changes in the position of the affected area due to patient's breathing. Various respiratory synchronization devices have been developed and evaluated to correct such changes in the position of the affected area due to respiration. However, all devices adopt a method to estimate the position of the affected area based on apparent physical changes due to the patient's breathing, and there is a problem in positioning correction accuracy in terms of individual differences among patients and uniformity of respiratory movement. There is.

  Therefore, a radioactive material made of heavy metal such as platinum, which has the property of emitting electron positron pairs when gamma rays hit, is placed in the vicinity of the affected area, irradiated with gamma rays from the outside of the patient, and applied to the radioactive material. A method has been proposed in which a positron pair is released, the electron positron pair is developed into an electromagnetic shower, and a tumor in the vicinity of the emitting material is irradiated to radiation treat the affected area (Patent Document 1: JP-A 2004-049884). According to Patent Document 1, it is described that the electron positron pair and the electromagnetic shower in which the electron positron pair is developed decrease in intensity with a predetermined distance, so that the influence on normal tissue surrounding a tumor can be suppressed. However, this method requires that the emitting material be pre-implanted, for example, inside the tumor, and the invasiveness is not necessarily low. In addition, it is difficult to embed the radiation material depending on the site.

  On the other hand, in recent years, thermal treatment (hyperthermia) for cancer that locally heats a tumor part has attracted attention, because the cancer tissue uses biological characteristics that it is more easily damaged by heat than normal tissue. It is done. When locally heating a tumor part, it has been attempted to heat the tumor part from outside the body by warm water, infrared rays, ultrasonic waves, microwaves and the like. However, although these methods can effectively heat the vicinity of the body surface, in the deep part of the body, it is difficult to effectively heat the normal tissue without damaging it. Magnetic lines of force can reach deep into the body without damaging the cells. Focusing on this, ferromagnetic microspheres are inserted into the body by a catheter or the like, the portion in which the ferromagnetic microspheres are embedded is placed in an alternating magnetic field, and heat generation due to hysteresis loss of the ferromagnetic microspheres is used. It has been proposed to locally heat the tumor site.

  And, as a magnetic composition suitable for hyperthermia, there is disclosed a magnetic composition comprising an amorphous alloy and a hydrophilic polymer. As this amorphous alloy, “one or more transition metals of Fe, Ni and Co, one or more metalloids of P, C, Si or B, and Cr and / or Mo A magnetic composition (for example, Patent Document 2: JP-A-6-245993), a magnetosensitive heating element mainly composed of iron-based oxide fine particles having a relative permeability of 100 to 2000 (for example, Patent Document 3: JP-A-11-57031) is a heat treatment body for thermal therapy mainly composed of a ferromagnetic layer coated on the outside of core fine particles, wherein the ferromagnetic layer is made of oxide, and its magnetic domain structure is A thermal treatment heating element (Patent Document 4: JP-A-2004-105722) has been proposed which is characterized in that at least one of a single magnetic domain and a pseudo single magnetic domain is formed.

  However, these methods also require that the heating element be pre-implanted inside, for example, a tumor, and the invasiveness is not necessarily low. In addition, it is difficult to embed the radiation material depending on the site.

Japanese Patent Application Publication No. 2004-049884 JP 6-245993 JP-A-11-57031 Japanese Patent Application Publication No. 2004-105722

  An object of the present invention is to provide a non-invasive or minimally invasive method for cancer treatment and magnetic particles and devices used therefor.

  The present inventors nonmagnetically or minimally introduce magnetic particles bound to an antibody against cancer cells into a patient's body, bind them to cancer cells, irradiate magnetic waves from the outside, and bind to cancer cells. It has been found that it can be killed by induction heating to complete the present invention.

  According to the present invention, by utilizing the antibody against cancer cells, it is possible to target and selectively bind only the cancer cells which are the affected area without binding the magnetic particles to normal cells of the patient. Then, by irradiating an electromagnetic wave of a specific frequency and output for a short time, only the magnetic particles bound to the cancer cells are inductively heated, and the cancer cells are instantaneously heated at a high temperature, thereby destroying the cell membrane and cell membrane The other protoplasts are shed or cells undergo apoptosis. Therefore, since the heat generation is completed before heat is conducted to the surroundings of the cancer cells to be heated, only the cancer cells can be heated and destroyed without destroying the normal part.

  The therapeutic method of the present invention nonmagnetically or minimally introduces the magnetic particles bound to the antibody into the patient's body, binds the magnetic particles to the cancer cells, and irradiates the cancer cells with electromagnetic radiation from the outside. It is characterized by induction heating to kill the bound magnetic body. In the present invention, "patient" broadly refers to the object to be treated, and when a patent on a treatment method is legally included, it includes humans, but if a patent on a treatment method is not approved, The treatment methods refer to only living organisms excluding "human".

The magnetic particles used in the present invention are not particularly limited as long as they are insoluble in an aqueous solution and exhibit magnetism. For example, Fe ₃ O ₄ , Fe ₂ O ₃ , FeO, γ-FeO, Co-γ-FeO, (NiCuZn) O · FeO, (CuZn) O · FeO, (MnZn) O · FeO, (NiZn) O · FeO, SrO · 6 FeO, BaO · 6 FeO, FeO coated with SiO ₂ (particle size about 200 A) [see Enzyme Microb. Tecnol., Vol 2, p. 2-10 (1980)], various polymer materials (nylon And magnetic particles produced in vivo, such as composite fine particles of polyacrylamide, polystyrene, etc.) and ferrite, and magnetic bacteria particles synthesized by bacterial cells in cells. Magnetic particles which can constitute so-called magnetic fluid are preferred. The magnetic particles are not limited to magnetite, and any magnetic material may be used if it is made of a material that generates heat by induction, and other iron compounds such as iron sulfide or alloys are also included. Other metals and the like include tungsten, alumina, nickel-chromium alloy, stainless steel, gold, carbon and the like, but magnetic particles which can be biologically produced are preferable. The diameter of the magnetic particles is preferably in the range of 2 nm to 200 μm, particularly 10 nm to 100 μm. When the diameter of the antibody-bound magnetic particles is less than 2 nm, the amount capable of carrying the antibody is small, the mobility to the magnetic force is lost, and when it exceeds 200 μm, the risk of vascular occlusion increases.

For example, magnetic bacteria were discovered in the 1970s in the United States, and a chain called magnetosome in which about 10 to 20 fine particles of magnetite (Fe ₃ O ₄ ) single crystal with a particle diameter of about 50 to 100 nm are linked in the cell body. Holding particles of By holding the magnetosomes, magnetic bacteria can sense the geomagnetism and recognize the direction of magnetic lines of force. Magnetic bacteria are microaerobic bacteria, and by sensing the geomagnetism, they can swim along aerobic lines from aerobic water surface to microaerobic sediment surface. Such magnetic bacteria are isolated as shown in ANALYTICAL CHEMISTRY, VOL. 63, No. 3, FEBRUARY 1, 1991 P268-P272, and can be cultured in large quantities. The magnetic particles in the magnetic bacteria are hexagonal columns, the particle diameter and shape are very uniform, the purity is high, and the magnetization of the cells containing the particles is about 50 emu / g in terms of fine particles. The coercivity is 230 Oe, and it has been confirmed that it has a single magnetic domain structure. In addition, since the surface of the magnetic particle is covered with an organic thin film, the magnetic particle has a characteristic that it hardly dissolves metal and exists stably, and also has excellent dispersibility in an aqueous solution.

  For example, as a method of extracting magnetic particles from magnetic bacteria, physical pressure crushing using a French press, alkali boiling, enzyme treatment, ultrasonic crushing treatment, etc. are known, and when large amounts of magnetic particles are obtained, , Ultrasonic crushing is suitable. After extraction, the magnetic particles may be separated by a magnet or the like.

  In addition, magnetic particles contained in migratory fish such as pigeons, migratory birds, salmon and sweetfish may be collected from living tissues, or preferably generated by genetic recombination.

  The antibodies are prepared by conventional methods to target antibodies against cancer. In the present invention, "an antibody against cancer cells" is a concept including all kinds of antibodies, peptides, DNA, sugar chains, glycolipids, etc. that bind to the outer surface of cancer cells. For example, in multiple myeloma cells, CD38 antigen, CD54 antigen, CD138 antigen, HM1.24 antigen, etc. are expressed on the cell surface. Therefore, antibodies against these antigens can be used as antibodies against cancer cells. The same is true for other cancers.

Although various techniques may be used to bind the magnetic particles to the antibody, one example is that the antibody used is mixed with the magnetic particles for a certain period of time to adsorb the antibody on the surface of the magnetic particles to adsorb the antibody. Particles can be obtained. In addition, by mixing the magnetic particles and cells, the magnetic particles can be adsorbed to the cells to obtain magnetic particles in a state of being bound to the cell membrane of cancer cells. Furthermore, anti-F (ab) ² fragment antibody can be made to act on this magnetic particle, it can remove from a cancer cell, and can obtain a single magnetic particle.

  Another example of binding magnetic particles to antibodies is a method in which all or part of magnetic particles is coated with a protein and antibodies are bound thereto. That is, an antibody having a binding site for both the coating protein and cancer cells is prepared and bound to the coating protein. Examples of coating proteins include serum albumin and casein, with serum albumin being preferred. Also, an additional coating material is provided in or bound to these coating proteins, into which one element of the specific binding pair is incorporated, and to the other element of the specific binding pair an antibody having a binding site for cancer cells is bound You may Examples of such typical specific binding pairs include biotin-streptavidin, antigen-antibody, receptor-hormone, receptor-logand, agonist-antagonist, lectin-sugars, protein A-antibody Fc, and avidin -Biotin is mentioned. For example, members of a specific binding pair are coupled to the coating material via a bifunctional linking compound. Exemplary difunctional linking compounds include succinimidyl-propiono-dithiopyridine (SPDP), and sulfosuccinimidyl-4- (maleimidomethylcyclohexane-1-carboxylate (SMCC), but heterofunctional linker compounds Other varieties are also available from Pierce, Rockford, Ill.

  As another example of a method for binding magnetic particles to antibodies, the magnetic particles may be coated with a gel layer containing an antibody. Such coated magnetic particles can be prepared, for example, by mixing magnetic particles with an aqueous solution containing an iron salt and a basic substance. The iron salt is not particularly limited, but iron (II) halides such as iron chloride and iron bromide can be suitably used. These iron salts may be used alone or in combination of two or more. An iron hydroxide gel layer is formed on the magnetic particles by using such an iron salt.

  As a density | concentration of the iron salt in the aqueous solution containing an iron salt, the range of 0.001-1 mol / L is preferable. When this concentration is less than 0.001 mol / L, the formation of a gel layer obtained is low, and when it is more than 1 mol / L, the thickness of the gel layer is increased. Preferably, it is in the range of 0.001 to 0.01 mol / L. As the basic substance of the aqueous solution containing the basic substance, any substance can be used as long as the pH of the system can be made neutral to alkaline in order to form iron hydroxide from iron salt, and in general, it is possible to use inorganic compounds. Alkali metal hydroxides and amines may be used, but compounds having an amino group, N-alkylamino group, N, N-dialkylamino group, such as ammonia, ethylamine, dimethylamine, sodium dimethylaminobenzoate, 2-dimethylaminoethanol, N-methyl-2-pyrrolidinone, sodium dimethylaminopropyl acetate, N, N-dimethylformamide, N, N-dimethylacrylamide oligomer, 1,1,4,7,10,10-hexamethyltriol Ethylenetetramine, 2- (dimethylamino) ethyl acrylate oligomer, N- (3- It is preferred to use such methylamino propyl) acrylamide oligomers. One of these basic substances may be used alone, or two or more thereof may be mixed and used. The concentration of the basic substance in the aqueous solution containing the basic substance has no meaning even at an excessively high concentration, and if the concentration is excessively low, it becomes difficult to form a gel layer from an iron salt, so 0.01 to 10.0 It is preferable that it is mol / L grade.

  As another example of the method of binding the magnetic particles to the antibody, a crosslinkable polymer compound may be used. For example, (A) magnetic particles or magnetic particles coated with the above-mentioned iron hydroxide gel layer, (B) an aqueous suspension containing ascorbic acid (hereinafter sometimes referred to as "component (B)") A high molecular compound (hereinafter sometimes referred to as "component (C)") obtained by suspending and mixing in an oily liquid, and then modifying this suspension with (C) a light-sensitive dye, and (D) an antibody (hereinafter referred to as "( (D) an aqueous solution containing a polymer compound modified with a light-sensitive dye and (D) an aqueous solution containing an antibody are suspended and mixed, and then this suspension is added to the suspension By irradiating with visible light, the polymer compound contained in the dispersed particles in the suspension can be obtained by photocrosslinking.

  The polymer compound modified with the light receiving system dye of (C) is used as a substance which generates a radical and is gelled by irradiation of visible light. Specific examples of the high molecular weight compound modified with xanthene dyes include collagen, fibronectin, gelatin, hyaluronic acid, keratanic acid, chondroitin sulfate, chondroitin sulfate, elastin, heparan sulfate, laminin, thrombospondin, Vitronectin, osteonectin, entactin, casein, polyethylene glycol, polypropylene glycol, polyglycidol, side chain esterified form of polyglycidol, polylactic acid, polyglycolic acid, polymer of cyclic ester, polyvinyl alcohol hydroxyethyl methacrylate and dimethylaminoethyl methacrylate Copolymer, copolymer of hydroxyethyl methacrylate and methacrylic acid, alginic acid, polyacrylamide, polydimethylacrylamide, polybi Rupiroridon and the like.

  As this light reception pigment | dye, the thing which light-receives the visible light region of wavelength 400-700 nm is mentioned, for example. Xanthine dyes, in particular eosin, are preferred, and eosinated gelatin is preferred as the light-sensitive dye-modified polymer compound. The eosinated gelatin is described in, for example, JP-A-2006-306786, and the same method can be taken in the present invention. When gelatin is modified with a xanthene dye, the number of xanthene dye molecules introduced per molecule of gelatin is preferably 10 or less, and particularly preferably 2 to 6. When the introduction number is more than 10, gelatin becomes poorly soluble in water and finally the gel particles become hard. The photocrosslinkable resin described in detail here is an example, and other photocrosslinkable polymers and thermally crosslinkable polymers can be used as well.

  The magnetic particles of the present invention can also be contained in a lipophilic liquid and used as a magnetic fluid. In this case, the solution is added and mixed as droplets using a capillary or the like, or suspended and dispersed using a stirrer such as a defoaming stirrer, and when adding an aqueous solution by dropping etc., or after adding a lipophilic liquid Preferably, the magnetic particles are well dispersed. Examples of the lipophilic liquid include hydrocarbons such as hexane, cyclohexane and liquid paraffin; halogenated hydrocarbons such as chloroform and methylene chloride; natural oils such as castor oil and olive oil; One type may be used alone, or two or more types may be mixed and used. To this lipophilic liquid may be added one or more kinds of surfactants such as polyoxyethylene cecil ether, oxyethylene oxypropylene copolymer, sodium dodecyl sulfate and the like, whereby the particles can be dispersed more finely. . The amount of surfactant added to the lipophilic liquid is preferably about 0.1 to 50% by weight. In addition, a thickener such as polyethylene glycol may be added to the lipophilic liquid. The amount of the thickener added to the lipophilic liquid is preferably about 0.1 to 20% by weight.

  The antibody-bound magnetic particles of the present invention prepared by any of the above methods or other methods are administered noninvasively or minimally invasively to a patient. For example, intravascular administration. After administration, the antibody-bound magnetic particles of the present invention can magnetically assemble antibody-bound magnetic particles to a disease site. This makes it possible to treat cancer more efficiently.

  In this case, as a method of applying the magnetic force, there are a method of applying directly from the body surface on the affected area and a method of applying from a device inserted into the body. As such a device, a device which penetrates into the tissue in the vicinity of the affected part percutaneously, an angiocatheter capable of applying a magnetic force in the vicinity of the affected part, or a device for indwelling in a blood vessel like a stent graft. There are magnets having magnetism, but not limited thereto.

  The antibody-bound magnetic particles remaining in blood are dialyzed because they can not bind to cancer cells in the patient's body. The blood is taken out and the antibody-bound magnetic particles are returned to the removal body using a magnet.

  The magnetic particles are irradiated with an electromagnetic wave having a frequency of 1 Hz to 3 THz and an output of 0.01 W to 10000 kW for 1 femtosecond or more and 24 hours or less in a state where the magnetic particles are bound to an affected area consisting of cancer cells of a treatment subject. The inductive heating of the magnetic particles heats the cancer cells to about 42 ° C. or more to destroy them. More preferably, the frequency is 380 kHz to 6 GHz, the output is 100 W to 1 kW, and the irradiation time is 5 minutes or less, and still more preferably the frequency of a commercially available high frequency power supply is 380 kHz, 400 kHz, 800 kHz, 2 MHz, 4 MHz, 13.56 MHz, 27.12 MHz 40.68 MHz, 60 MHz, 60.68 MHz, 100 MHz, 150 MHz, 200 MHz, 2.45 GHz, 5.6 GHz, and an output of 100 to 300 W are available. However, these values can be changed depending on the type, site, and condition of the applied cancer. The electromagnetic wave to be applied is not limited to a sine wave, and may be a pulse rectangular wave. Such a method of treatment comprises, for example, magnetic particles bound to an antibody against a cancer cell that selectively binds to the magnetic particle to the cancer cell, and the magnetic particle bound to an affected area comprising cancer cells of a patient to be treated. The apparatus may be provided with an induction heating means for irradiating the magnetic particles with an electromagnetic wave such as the frequency, and the apparatus for induction heating the magnetic particles to heat and destroy the cancer cells. Such an apparatus can be manufactured by installing an electromagnetic wave source in the irradiation apparatus comprised with the high frequency shielding board. In the present invention, the term "induction heating" refers to the general phenomenon in which magnetic particles generate heat due to the application of an electromagnetic wave or a magnetic field, and the heating may be caused by hysteresis loss or Joule heat. Also includes "heating". In addition, “destruction” of cancer cells includes any of apoptosis caused by heating, and a mechanism in which cell membranes are physically destroyed to cause cell destruction.

  Hereinafter, the present invention will be more specifically described by way of examples. In the following examples, multiple myeloma cell line KMS28PE cells expressing 80% or more of CD54 antigen were used as cancer cells. Cancer cell binding antibodies are antibodies to the CD54 antigen.

Comparative Examples 1 and 2
Magnetic particles for magnetic fluid (ferrite based super paramagnetic material; average particle diameter: 0.02 μm) were mixed with cancer cell-bound antibody and serum albumin to produce cancer cell-bound antibody-attached magnetic particles. The cancer cells cultured on IMDM-containing agar medium were brought into contact with the solution containing the cancer cell-bound antibody-attached magnetic particles, and after 3 hours, the solution was removed and washed with a culture solution (Example). A solution containing only magnetic particles (without attachment of a cancer cell-binding antibody) was brought into contact as Comparative Example 1, and after 3 hours, the solution was removed and washed with a culture solution, and as Comparative Example 2, the magnetic particles were removed. The solution was brought into contact, and after 3 hours, the solution was removed and washed with culture medium.
It was irradiated with an electromagnetic wave with a frequency of 13.56 MHz, 27.12 MHz, 40.68 MHz and an output of 100 W for 5 seconds to 60 seconds, and the survival rate of cancer cells was examined. In this example, substantially all cells were killed. In contrast, in Comparative Example 1, many cells were not killed, and in Comparative Example 2, almost all cells survived.

Comparative Examples 3 to 4
Iron (II) tetrahydrate (JIS special grade reagent) was dissolved in purified water to prepare a 0.1 M solution. Ammonia water is dropped into a mixed solution of 5.0 mL of the obtained solution, magnetic bacteria-derived magnetic particles (average particle diameter 50 to 100 nm) and antibody-containing solution to adjust the pH of the aqueous phase to about 9.0, Cancer cell-bound antibody attached magnetic particles with a diameter of about 1 μm were obtained.
The cancer cells cultured on IMDM-containing agar medium were brought into contact with the solution containing the cancer cell-bound antibody-attached magnetic particles, and after 3 hours, the solution was removed and washed with a culture solution (Example). A solution containing only magnetic particles (without attachment of a cancer cell-binding antibody) was brought into contact as Comparative Example 3, and after 3 hours, the solution was removed and washed with a culture solution, and as Comparative Example 4, the magnetic particles were removed. The solution was brought into contact, and after 3 hours, the solution was removed and washed with culture medium.
This was irradiated with an electromagnetic wave of 13.56 MHz, 27.12 MHz, 40.68 MHz, and an output of 100 W for 5 seconds to 60 seconds, and the survival rate of cancer cells was examined. In the example, substantially all cells were killed. On the other hand, in Comparative Example 3, many cells were not killed, and in Comparative Example 4, almost all cells survived.

Comparative Examples 5 to 6
In order to examine the induction effect by magnetic force, after the solution of Comparative Example 3 is brought into contact with cancer cells, the state in which magnetic particles are collected near the cancer cells with a strong magnet (strong neodymium magnet marketed as stationery) The treatment was performed (comparative example 5). As a precaution, the same experiment was performed on the solution of Comparative Example 4 as a control experiment (Comparative Example 6). As a result, most of the cancer cells were killed in Comparative Example 5, whereas almost none were killed in Comparative Example 6. Therefore, in vivo, magnetic particles can be more efficiently bound to cancer cells by combining antibody binding and magnetic force guidance.

Claims (8)

Magnetic particles bound to an antibody against cancer cells are introduced noninvasively or minimally into a patient's body, bound to cancer cells, and irradiated from outside with an electromagnetic wave or a magnetic field applied to bind to cancer cells. A method of treating cancer characterized by induction heating and killing. The method for treating cancer according to claim 1, further comprising the step of magnetically guiding the magnetic particle to the vicinity of a cancer cell after introducing the magnetic particle into the patient's body. The method for treating cancer according to claim 1 or 2, wherein the magnetic particles are of biological origin. The magnetic particle for use in the method for treating cancer according to any one of claims 1 to 3, wherein the antibody-containing serum albumin layer is formed on the magnetic particle by mixing the magnetic particle with a serum albumin and a cancer antibody containing solution. The method for treating cancer according to any one of claims 1 to 3, wherein the antibody-containing iron hydroxide gel layer is formed on the magnetic particles by mixing the magnetic particles with an aqueous solution containing an iron salt and a basic substance and a cancer antibody-containing solution. Magnetic particles for use. The treatment for cancer according to any one of claims 1 to 3, wherein the photo- or thermally-crosslinkable polymer layer is provided on the magnetic particle alone or on the magnetic particle having an iron hydroxide gel layer, and the crosslinked polymer layer contains a cancer antibody. Magnetic particles for use in the method. A means for irradiating / applying a magnetic field to induce / dielectric / magnetically heat the magnetic particles according to any one of claims 4 to 6 is provided, and the magnetic particles are heated to heat and destroy the cancer cells. A device for use in any of the following three cancer treatment methods. The apparatus according to claim 7, further comprising a magnetic member for guiding magnetic particles.