Magnetic graphene nanocapsule and preparation method and application thereof

Abstract

The application belongs to the technical field of biomedical application of nanomaterials, and discloses a magnetic graphene nanocapsule as well as a preparation method and application thereof. The application provides a magnetic graphene nanocapsule, wherein the magnetic graphene nanocapsule is of a core-shell structure, the core is a magnetic metal, and the shell layer is a magnetic graphene nanocapsule, compared with traditional magnetic metal oxides, the heat production capacity and acid resistance are significantly enhanced, and stable hyperthermia conditions can be provided in the stomach. The application further provides a preparation method of the magnetic graphene nanocapsule, wherein inexpensive and readily available raw materials such as metal chloride and nitrate are used, the synthesis conditions are simple, and the method is suitable for mass production. The obtained magnetic graphene nanocapsule can enter a specified site through oral administration, such a drug administration mode can avoid the problems of liver accumulation and side effects of nanoparticles after entering the blood, and potential toxicity of nanoparticles after entering the systemic circulation is avoided.

Description

TECHNICAL FIELD

[0001] The present application relates to the biomedical application field of nanomaterials, and in particular to a magnetic graphene nanocapsule and a preparation method and application thereof. BACKGROUND

[0002] As a tumor treatment method, hyperthermia can induce cancer cell apoptosis by changing the cell environment temperature to maintain the temperature range between 42 DEG C and 47 DEG C, and has achieved good clinical treatment effect, and is currently widely used in the treatment of breast cancer, bladder cancer, head and neck cancer, melanoma and rectal cancer. However, the stomach has its unique physiological characteristics compared with other organs: 1, it is deeply buried in the abdominal cavity of the human body, and the conventional means is difficult to act on the deep tissue; 2, the stomach cavity contains rich digestive enzymes and strong corrosive gastric acid, which greatly limits the application of conventional heat-producing reagents. The traditional hyperthermia methods such as perfusion of hot water, radio frequency, microwave, high intensity focused ultrasound and photo-thermal conversion are difficult to perform hyperthermia on the stomach from the inside to the outside. Magnetic hyperthermia is a minimally invasive hyperthermia method, which has no penetration depth limit, making it a competitive method for stomach hyperthermia. The principle of heat generation is to use the relaxation phenomenon of superparamagnetic nanoparticles in the alternating magnetic field to complete the conversion of magnetic energy to heat energy. The general use of magnetic hyperthermia in the biomedical field is iron oxide nanoparticles (chemical formula Fe3O4), and the challenges of using it for stomach magnetic hyperthermia are: 1, low magnetic heat conversion efficiency, and the specific loss power (SLP) is difficult to break through 100 W / g; 2, the commonly used iron oxide nanoparticles are unstable under acidic conditions, so that the specified treatment temperature cannot be reached and potential biological toxicity may be produced. Therefore, it has important scientific significance and practical application value to develop a magnetic hyperthermia technology that can stably provide efficient hyperthermia effect in the stomach. SUMMARY

[0003] Therefore, the present application provides a magnetic graphene nanocapsule and a preparation method and application thereof, to solve the problems of low magnetic heat conversion efficiency of the existing iron oxide nanoparticles used in magnetic hyperthermia, and the inability to stably exist in the stomach cavity, the inability to reach the specified treatment temperature and the potential biological toxicity.

[0004] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0005] The present application provides a preparation method of a magnetic graphene nanocapsule, comprising the following steps:

[0006] (1) mixing a magnetic metal salt solution and a fumed silica solution, then evaporating, and then sequentially performing heat treatment and in-situ growth to obtain a catalyst;

[0007] (2) mixing the catalyst with a hydrofluoric acid solution to etch, to obtain a magnetic graphene nanocapsule.

[0008] As a preferred, in the step (1), the magnetic metal salt is ferric chloride, ferric nitrate, cobalt chloride, cobalt nitrate, nickel chloride or nickel nitrate; the solvent of the magnetic metal salt solution is methanol; the molar volume ratio of the magnetic metal salt and methanol is 0.0036 mol: 10-20 mL.

[0009] As a preferred, in the step (1), the particle size of the fumed silica is 200-500 nm; the fumed silica and methanol are ultrasonically mixed to obtain a fumed silica solution; the mass-volume ratio of the fumed silica and methanol is 1-2 g: 200-500 mL; the frequency of the ultrasonic mixing is 40-50 kHz, and the time of the ultrasonic mixing is 30-60 min.

[0010] As a preferred, the purity of the methanol in the magnetic metal salt solution and the fumed silica solution is independently ≥99.8%.

[0011] As a preferred, in the step (1), the temperature of the evaporation is 50-60℃, and the rotation speed of the evaporation is 80-100 r / min.

[0012] As a preferred, in the step (1), the heat treatment is carried out under the condition of a reducing gas, the flow rate of the reducing gas is 50-100 cfm; the temperature of the heat treatment is 810-900℃, the time of the heat treatment is 20-30 min, the heating rate for heating to the temperature of the heat treatment is 10-20℃ / min; the in-situ growth is carried out under the atmosphere of methane, the flow rate of the methane is 200-300 cfm, the temperature of the in-situ growth is 810-900℃, and the time of the in-situ growth is 5-10 min.

[0013] As a preferred, in the step (1), the product obtained by the evaporation is ground before the heat treatment.

[0014] As a preferred, the molar volume ratio of the magnetic metal salt in the step (1) and the hydrofluoric acid solution in the step (2) is 0.0012 mol: 8-15 mL; the hydrofluoric acid solution is an aqueous solution of hydrofluoric acid, and the volume concentration of the hydrofluoric acid solution is 10-20%.

[0015] The application also provides the magnetic graphene nanocapsule prepared by the preparation method of the magnetic graphene nanocapsule.

[0016] The application also provides the application of the magnetic graphene nanocapsule in magnetic hyperthermia.

[0017] According to the above technical solution, compared with the prior art, the application has the following beneficial effects:

[0018] (1) The application in-situ grows magnetic graphene nanocapsules with a magnetic metal as an inner core and graphene as a shell layer by a chemical vapor deposition method, compared with traditional magnetic metal oxides, the heat production capacity and acid resistance are significantly enhanced, and stable hyperthermia conditions can be provided in the stomach;

[0019] (2) The raw materials of the application are cheap and easily available raw materials such as metal chloride salt and nitrate salt, the synthesis conditions are simple, and mass production is suitable;

[0020] (3) The obtained magnetic graphene nanocapsules enter the designated site by oral administration, such a drug administration method can avoid the problems of side effects caused by the enrichment of nanoparticles in the liver after entering the blood, and most of the magnetic heat reagents are enriched in the stomach, so that the dosage of the magnetic heat reagents can be reduced, and the potential toxicity of nanoparticles entering the human circulation can be avoided. BRIEF DESCRIPTION OF DRAWINGS

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only embodiments of the application, and other drawings can be obtained by those skilled in the art without creative labor on the basis of the provided drawings.

[0022] Figure 1 The scanning transmission electron microscope images of the surface morphology of the magnetic graphene nanocapsules obtained in Examples 1, 3 and 5 of the application, wherein a is the Fe@G magnetic graphene nanocapsules obtained in Example 1, b is the Co@G magnetic graphene nanocapsules obtained in Example 3, and c is the Ni@G magnetic graphene nanocapsules obtained in Example 5;

[0023] Figure 2 The element distribution images and energy dispersion spectra of the magnetic graphene nanocapsules obtained in Examples 1, 3 and 5 of the application, wherein a is the element distribution image of the magnetic graphene nanocapsules obtained in Examples 1, 3 and 5, and b is the energy dispersion spectrum of the magnetic graphene nanocapsules obtained in Examples 1, 3 and 5;

[0024] Figure 3 The magnetic hysteresis loop test curves of the magnetic graphene nanocapsules obtained in Examples 1, 3 and 5 of the application;

[0025] Figure 4 The heat production rate images and SLP values of the magnetic graphene nanocapsules obtained in Examples 1, 3 and 5 of the application under an alternating magnetic field with a magnetic field strength of 20 kA / m and a frequency of 340 kHz, wherein a corresponds to the magnetic graphene nanocapsules obtained in Example 1, b corresponds to the magnetic graphene nanocapsules obtained in Example 3, and c corresponds to the magnetic graphene nanocapsules obtained in Example 5;

[0026] Figure 5 MRI-T2 weighted imaging of the stomach of a mouse before and after intragastrical administration of the magnetic graphene nanocapsules obtained in Example 1 of the present application, wherein a is the MRI-T2 weighted imaging of the stomach of the mouse before intragastrical administration, and b is the MRI-T2 weighted imaging of the stomach of the mouse after intragastrical administration;

[0027] Figure 6 H&E staining section of the stomach of a mouse, wherein a is the H&E staining section of the stomach of a mouse without magnetic hyperthermia, and b is the H&E staining section of the stomach of a mouse after magnetic hyperthermia with the magnetic graphene nanocapsules obtained in Example 1 of the present application;

[0028] Figure 7 Comparison of the magnetic hyperthermia of Fe3O4 and the magnetic graphene nanocapsules obtained in Example 1 of the present application in 1M hydrochloric acid solution, wherein in Figures a, b and c, the right side is the magnetic graphene nanocapsules obtained in Example 1 of the present application, and the left side is Fe3O4; in Figure d, the left side is the magnetic graphene nanocapsules obtained in Example 1 of the present application, and the right side is Fe3O4; a is the thermal imaging after 10 min in a magnetic field, b is the thermal imaging after 20 min in a magnetic field, c is the thermal imaging after 30 min in a magnetic field, and d is the bright field imaging after 30 min in a magnetic field. DETAILED DESCRIPTION

[0029] The present application provides a preparation method of magnetic graphene nanocapsules, comprising the following steps:

[0030] (1) mixing a magnetic metal salt solution and a fumed silica solution, then evaporating, and then sequentially performing heat treatment and in-situ growth to obtain a catalyst;

[0031] (2) mixing the catalyst with a hydrofluoric acid solution to perform etching, to obtain the magnetic graphene nanocapsules.

[0032] In the present application, in step (1), the magnetic metal salt is preferably ferric chloride, ferric nitrate, cobalt chloride, cobalt nitrate, nickel chloride or nickel nitrate, and is further preferably ferric nitrate, cobalt chloride or nickel nitrate; the solvent of the magnetic metal salt solution is preferably methanol; and the molar volume ratio of the magnetic metal salt to methanol is preferably 0.0036 mol: 10-20 mL, and is further preferably 0.0036 mol: 12-15 mL.

[0033] In the present application, in the step (1), the particle size of the fumed silica is preferably 200-500 nm, and further preferably 250-400 nm; the fumed silica and the methanol are ultrasonically mixed to obtain a fumed silica solution; the mass-volume ratio of the fumed silica and the methanol is preferably 1-2 g: 200-500 mL, and further preferably 1.2-1.6 g: 300-400 mL; the frequency of the ultrasonic mixing is preferably 40-50 kHz, and further preferably 42-45 kHz; and the time of the ultrasonic mixing is preferably 30-60 min, and further preferably 40-50 min.

[0034] In the present application, the purity of the methanol in the magnetic metal salt solution and the fumed silica solution is independently preferably ≥ 99.8%, and further preferably ≥ 99.9%.

[0035] In the present application, in the step (1), the evaporation temperature is preferably 50-60℃, and further preferably 55-58℃; and the evaporation rotation speed is preferably 80-100 r / min, and further preferably 85-95 r / min.

[0036] The evaporation is performed on a rotary evaporator, and the heating mode during the evaporation is water bath heating.

[0037] In the present application, in the step (1), the heat treatment is performed under the condition of a reducing gas; the reducing gas is preferably hydrogen; the flow rate of the reducing gas is preferably 50-100 cfm, and further preferably 60-90 cfm; the heat treatment temperature is preferably 810-900℃, and further preferably 820-880℃; the heat treatment time is preferably 20-30 min, and further preferably 25-28 min; the temperature rising rate to the heat treatment temperature is preferably 10-20℃ / min, and further preferably 12-18℃ / min; the in-situ growth is performed in a methane atmosphere, and the flow rate of the methane is preferably 200-300 cfm, and further preferably 220-260 cfm; the in-situ growth temperature is preferably 810-900℃, and further preferably 850-880℃; and the in-situ growth time is preferably 5-10 min, and further preferably 6-8 min.

[0038] In the present application, in the step (1), the product obtained by evaporation is ground before the heat treatment; and the particle size of the ground product is preferably 10-100 μm, and further preferably 20-70 μm.

[0039] In the present application, in the step (1), the product obtained by in-situ growth is subjected to a cooling treatment before obtaining the catalyst; and the cooling rate is preferably 20-50℃ / min, and further preferably 30-40℃ / min.

[0040] In the present application, the molar volume ratio of the magnetic metal salt in step (1) to the hydrofluoric acid solution in step (2) is preferably 0.0012 mol: 8-15 mL, and further preferably 0.0012 mol: 9-12 mL; the hydrofluoric acid solution is an aqueous solution of hydrofluoric acid, and the volume concentration of the hydrofluoric acid solution is preferably 10-20%, and further preferably 11-15%.

[0041] In the present application, the etching time in step (2) is preferably 10-14 h, and further preferably 11-13 h.

[0042] In the present application, the hydrofluoric acid solution in step (2) functions to etch the fumed silica.

[0043] In the present application, after the etching in step (2) is completed, the product obtained by etching is magnetically recovered to obtain magnetic powder, the magnetic powder is washed to neutral, and then magnetically recovered to obtain the magnetic graphene nanocapsule.

[0044] The present application realizes the preparation of the magnetic graphite nanocapsule by chemical vapor deposition, uses a magnetic metal salt (chloride or nitrate of iron, cobalt or nickel) as a raw material, and forms a magnetic metal nanoparticle in a tube furnace by using the reducing property of hydrogen. The magnetic metal nanoparticle has a higher saturation magnetization than a magnetic metal oxide, and the saturation magnetization is in a proportional relationship with the SLP value, so the metal nanoparticle has a better magnetic heat conversion efficiency than the metal oxide. In addition, the present application forms a core-shell structure by growing a dense graphene layer in situ, and separates the magnetic metal nanoparticle from the corrosive acid and enzyme in the external environment, so as to achieve the purpose of protection.

[0045] The present application also provides the magnetic graphene nanocapsule prepared by the preparation method of the magnetic graphene nanocapsule.

[0046] The present application also provides the application of the magnetic graphene nanocapsule in magnetic heat therapy.

[0047] In the present application, the application of the magnetic graphene nanocapsule in magnetic heat therapy includes the following steps:

[0048] The magnetic graphene nanocapsule is filled into a gastric capsule; the part to be treated is placed in a magnetic heat coil, and a magnetic field is applied.

[0049] In the present application, the filling volume of the magnetic graphene nanocapsule is preferably 50-70% of the volume of the gastric capsule, and further preferably 55-66%.

[0050] The filling volume of the magnetic graphene nanocapsule is determined to ensure that it can sufficiently fill the gastric capsule.

[0051] In the present application, the frequency of the magnetic field is preferably 280-370 kHz, further preferably 300-350 kHz; the strength of the magnetic field is preferably 1300-1700 A / m, further preferably 1400-1600 A / m; the product of the strength and frequency of the magnetic field is preferably ≤4.85×10 8 A / m, further preferably ≤4.84×10 8 A / m.

[0052] The determination of the product of the strength and frequency of the magnetic field can avoid the generation of eddy current heat, ensuring the safety to biological tissues.

[0053] In the present application, the time for applying the magnetic field is preferably 20-40 min, further preferably 25-35 min.

[0054] The technical solutions provided by the present application are described in detail below in conjunction with examples, but they should not be understood as limiting the scope of protection of the present application.

[0055] Example 1

[0056] Preparation of Fe@G magnetic graphene nanocapsules:

[0057] 0.0036 mol Fe(NO3)3·9H2O was added to 10 mL of methanol with a purity of 99.8%, and an iron nitrate methanol solution was obtained by dissolving. Then 1 g of fumed silica (particle size 250 nm) was added to 300 mL of methanol with a purity of 99.8%, and ultrasonic dispersion was performed at a frequency of 45 kHz for 30 min to make the solution free of precipitates, obtaining a fumed silica methanol solution; then the iron nitrate methanol solution was added to the fumed silica methanol solution for mixing, and then the methanol solvent was evaporated on a rotary evaporator at a rotation speed of 80 r / min at 50℃, obtaining a powder. The obtained powder was ground to a particle size of 10 μm and then placed in a tube furnace, and hydrogen was introduced at a flow rate of 100 cfm for protection, the temperature was raised to 860℃ at a rate of 20℃ / min, and then kept for 20 min, and then methane was introduced at a flow rate of 300 cfm for in-situ growth for 10 min, the temperature for in-situ growth was 860℃, and then the temperature was lowered to room temperature at a rate of 20℃ / min, obtaining a catalyst; the obtained catalyst was added to 30 mL of an aqueous solution of hydrofluoric acid with a volume concentration of 20%, and etched for 12 h, and then the magnetic powder was recovered by magnetic attraction after the reaction was completed, washed with ultrapure water until neutral, and then recovered by magnetic attraction, obtaining Fe@G magnetic graphene nanocapsules.

[0058] The performance test results of the Fe@G magnetic graphene nanocapsules obtained in this example are as follows:

[0059] The prepared Fe@G magnetic graphene nanocapsules were characterized by scanning transmission electron microscopy, and the results are as follows: Figure 1a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure. Figure 1 a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure. Figure 2 a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure. Figure 2 a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure.

[0060] a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure. Figure 3 a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure. Figure 3 a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure.

[0061] a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure. Figure 4 a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure. Figure 4 a. It can be known from Figure 2 that the obtained Fe@G magnetic graphene nanocapsules have obvious metal crystal lattices and outer graphene layers, which indicates that the obtained Fe@G magnetic graphene nanocapsules have a core-shell structure.

[0062] Example 2

[0063] The difference between this embodiment and Example 1 is that Fe(NO3)3·9H2O is replaced by FeCl3·6H2O, and the others are the same as Example 1.

[0064] Example 3

[0065] Preparation of Co@G magnetic graphene nanocapsules:

[0066] Co(NO3)2·6H2O was dissolved in 15 mL of methanol with a purity of 99.9% to obtain a cobalt nitrate methanol solution. 1 g of fumed silica with a particle size of 400 nm was added to 350 mL of methanol with a purity of 99.8%, and ultrasonic dispersion was performed at a frequency of 46 kHz for 40 min to obtain a fumed silica methanol solution without precipitation in the solution. The cobalt nitrate methanol solution was then added to the fumed silica methanol solution, and then the methanol solvent was evaporated on a rotary evaporator at a rotation speed of 90 r / min at 55 ℃ to obtain a powder. The obtained powder was ground to a particle size of 50 μm and then placed in a tube furnace, and the temperature was raised to 850 ℃ at a rate of 19 ℃ / min under the protection of hydrogen with a flow rate of 80 cfm. After keeping the temperature at 850 ℃ for 25 min, methane with a flow rate of 250 cfm was introduced for in-situ growth for 15 min, and then the temperature was lowered to room temperature at a rate of 35 ℃ / min to obtain a catalyst. The obtained catalyst was etched in 32 mL of an aqueous solution of hydrofluoric acid with a volume concentration of 18% for 12 h, and after the reaction was completed, the magnetic powder was recovered by magnetic attraction, washed with ultrapure water until neutral, and then recovered by magnetic attraction to obtain Co@G magnetic graphene nanocapsules.

[0067] The performance test results of the Co@G magnetic graphene nanocapsules obtained in the example are as follows:

[0068] The Co@G magnetic graphene nanocapsules prepared were characterized by scanning transmission electron microscopy, and the results are shown in Figure 1 b. As can be seen from Figure 1 b, the Co@G magnetic graphene nanocapsules obtained in the application have a clear metal lattice and an outer graphene layer, indicating that the Co@G magnetic graphene nanocapsules obtained are of core-shell structure. Element EDS analysis was performed, and the results are shown in Figure 2 . As can be seen from Figure 2 , the Co@G magnetic graphene nanocapsules obtained are mainly composed of cobalt elements, have high purity, and do not produce other impurities.

[0069] The Co@G magnetic graphene nanocapsules prepared were subjected to hysteresis loop testing, and the results are shown in Figure 3 . As can be seen from Figure 3 , the saturation magnetization of the Co@G magnetic graphene nanocapsules obtained in the example is 116 emu / g.

[0070] The Co@G magnetic graphene nanocapsules prepared were diluted with water to a concentration of 5 mg / mL, placed in an alternating magnetic field (the strength of the applied magnetic field was 20 kA / m, and the frequency was 340 kHz), and subjected to in-vitro magnetic heating test, and the results are shown in Figure 4 . As can be seen from Figure 4It can be seen that the SLP value of the Co@G magnetic graphene nanocapsule obtained by calculation is 398.2 W / g, indicating that the magnetic heat performance of the Co@G magnetic graphene nanocapsule is excellent.

[0071] Example 4

[0072] The difference between the present example and Example 3 is that Co(NO3)2·6H2O is replaced by CoCl2·6H2O, and the others are the same as those in Example 3.

[0073] Example 5

[0074] Preparation of Ni@G magnetic graphene nanocapsule:

[0075] 0.0036 mol of Ni(NO3)2·6H2O was added to 13 mL of methanol with a purity of 99.8% to obtain a methanol solution of nickel nitrate. Then, 1 g of fumed silica with a particle size of 500 nm was added to 360 mL of methanol with a purity of 99.9%, and ultrasonic dispersion was performed at a frequency of 43 kHz for 50 min to make the solution free of precipitation, thereby obtaining a fumed silica methanol solution. Then, the methanol solution of nickel nitrate was added to the fumed silica methanol solution for mixing, and then the methanol solvent was evaporated on a rotary evaporator at a rotation speed of 100 r / min at 60 ℃, thereby obtaining a powder. The obtained powder was ground to a particle size of 80 μm and then placed in a tube furnace, and hydrogen with a flow rate of 90 cfm was used for protection, the temperature was raised to 900 ℃ at a temperature raising rate of 20 ℃ / min, and then the temperature was kept for 20 min. Then, methane with a flow rate of 300 cfm was introduced for in-situ growth for 10 min, the temperature for in-situ growth was 900 ℃, and then the temperature was lowered to room temperature at a temperature lowering rate of 50 ℃ / min, thereby obtaining a catalyst. The obtained catalyst was added to 30 mL of an aqueous solution of hydrofluoric acid with a volume concentration of 15% for etching for 12 h, and then the magnetic powder was recovered by magnetic attraction after the reaction was completed. The magnetic powder was washed with ultrapure water until it was neutral, and then the Ni@G magnetic graphene nanocapsule was recovered by magnetic attraction.

[0076] The performance test results of the Ni@G magnetic graphene nanocapsule obtained in the present example are as follows:

[0077] The Ni@G magnetic graphene nanocapsule prepared was characterized by scanning transmission electron microscopy, and the results are shown in Figure 1 c. As shown in Figure 1 c, the Ni@G magnetic graphene nanocapsule obtained in the present application can have a clear metal crystal lattice and an outer graphene layer, indicating that the Ni@G magnetic graphene nanocapsule obtained has a core-shell structure. Element EDS analysis was performed, and the results are shown in Figure 2 . As shown in Figure 2 , the Ni@G magnetic graphene nanocapsule obtained mainly contains nickel elements, has high purity, and does not produce other impurities.

[0078] The prepared Ni@G magnetic graphene nanocapsules were subjected to hysteresis loop test, and the results are shown in Figure 3 From the results, it can be seen that the saturation magnetization of the Ni@G magnetic graphene nanocapsules obtained in the example is 116 emu / g. Figure 3

[0079] The prepared Ni@G magnetic graphene nanocapsules were diluted with water to a concentration of 5 mg / mL, and were placed in an alternating magnetic field (the strength of the applied magnetic field was 20 kA / m, and the frequency was 340 kHz) for in-vitro magnetic heating test, and the results are shown in Figure 4 From the results, it can be seen that the SLP value of the Ni@G magnetic graphene nanocapsules is 223.1 W / g, indicating that the magnetic heating performance of the obtained Ni@G magnetic graphene nanocapsules is excellent. Figure 4

[0080] Example 6

[0081] The difference between the example and Example 5 is that Ni(NO3)2·6H2O is replaced by NiCl2·6H2O, and the rest is the same as Example 5.

[0082] The Fe@G magnetic graphene nanocapsules obtained in Example 1 were subjected to performance test, and the details are as follows:

[0083] 1. In order to verify that the magnetic graphene nanocapsules as a magnetic heating reagent can be retained in the stomach through oral administration, the Fe@G magnetic graphene nanocapsules obtained in Example 1 were subjected to mouse gavage experiment for verification. The verification was approved by the Animal Ethics Committee of Hunan University.

[0084] The verification method is as follows: BALB / C mice were subjected to gavage operation (the concentration of the aqueous solution of the Fe@G magnetic graphene nanocapsules was 0.2 mg / mL, and the gavage volume was 200 uL per mouse), and the gastric retention state of the Fe@G magnetic graphene nanocapsules was characterized by nuclear magnetic resonance imaging, and the results are shown in Figure 5 .

[0085] From the results, it can be seen that Figure 5 Figure 5 a is the imaging graph of the mouse before gavage, and the red circle position is the stomach, at which time the stomach signal is a bright signal. Figure 5 b is the imaging graph of the mouse 20 min after gavage, and the red circle position is the stomach, at which time the stomach signal becomes a dark signal due to the presence of the magnetic graphene nanocapsules. It shows that the magnetic graphene nanocapsules obtained in the application can be retained in the stomach for a long time.

[0086] 2. In order to verify the gastric hyperthermia capacity of the magnetic graphene nanocapsules, the Fe@G magnetic graphene nanocapsules obtained in Example 1 were subjected to mouse gastric hyperthermia experiment for verification. The experiment was approved by the Animal Ethics Committee of Hunan University. ​​​

[0087] The verification method was as follows: BALB / c mice were administered a gavage (Fe@G magnetic graphene nanocapsules at an aqueous solution concentration of 0.2 mg / mL, gavage volume 200 μL / mouse). After the Fe@G magnetic graphene nanocapsules remained in the mouse stomach, the mice were placed in an alternating magnetic field (magnetic field strength 20 kA / m, frequency 340 kHz) for in vivo magnetocaloric heating test. The heating time was 30 min. After mouse sacrifice, the stomach was removed, sectioned, and H&E stained. The results are as follows: Figure 6 As shown.

[0088] Depend on Figure 6 It can be seen that, Figure 6 Image a is a slice of a normal mouse stomach. The gastric epithelial structure of the mucosa is intact, the gastric pits are clearly visible, the epithelial cells are tightly arranged, the gastric glands in the lamina propria are abundant, and the chief cells and parietal cells have normal morphology and structure. Figure 6 Image b shows a slice after 30 minutes of magnetothermal therapy. Multiple epithelial cell detachments are visible in the mucosal layer, mixed with Fe@G magnetic graphene nanocapsules (black arrows). This indicates that the magnetic graphene nanocapsules obtained in this invention can perform magnetothermal therapy in the stomach, laying the foundation for the development of high-performance gastric magnetothermal therapy reagents.

[0089] 3. The stability of the Fe@G magnetic graphene nanocapsules obtained in Example 1 with iron oxide was tested.

[0090] Test method: Fe@G magnetic graphene nanocapsules and iron(III) oxide were placed in 20 mL of 1 M hydrochloric acid solution, respectively. Both were then placed in an alternating magnetic field (20 kA / m, 340 kHz frequency) for magnetocaloric heating test. The results are as follows: Figure 7 As shown.

[0091] Depend on Figure 7 It can be seen that, Figure 7 The display shows that after being in a magnetic field for 10 minutes, both test tubes reached the same temperature. Figure 7 b shows that after being in a magnetic field for 20 minutes, the temperature of the test tube containing iron(III) oxide on the left decreased and the particles began to decompose, while the test tube on the right was unaffected. Figure 7 c shows that after being in a magnetic field for 30 minutes, the temperature of the test tube containing iron(III) oxide on the left dropped significantly and the particles decomposed, while the test tube on the right was unaffected. Figure 7 Figure d shows that after being placed in a magnetic field for 30 minutes, most of the iron(III) oxide (Fe3O4) had decomposed, presenting a clear green solution, while the Fe@G magnetic graphene nanocapsules remained unchanged. This indicates that the magnetic graphene nanocapsules obtained in this invention are more stable under acidic conditions with magnetocaloric heating than the commonly used magnetocaloric reagent, iron(III) oxide.

[0092] The above merely describes the preferred embodiments of the present application, and it should be pointed out that, for those skilled in the art, several improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as falling within the protection scope of the present application.

Claims

1. A method for preparing magnetic graphene nanocapsules, characterized in that, The method comprises the following steps: (1) mixing a magnetic metal salt solution and a fumed silica solution, evaporating, then sequentially performing heat treatment and in-situ growth to obtain a catalyst; (2) mixing the catalyst with a hydrofluoric acid solution to perform etching, and obtaining a magnetic graphene nanocapsule; In the step (1), the magnetic metal salt is ferric chloride, ferric nitrate, cobalt chloride, cobalt nitrate, nickel chloride or nickel nitrate; the solvent of the magnetic metal salt solution is methanol; the molar volume ratio of the magnetic metal salt to methanol is 0.0036 mol: 10-20 mL; In the step (1), the particle size of the fumed silica is 200-500 nm; the fumed silica and methanol are ultrasonically mixed to obtain a fumed silica solution; The mass-volume ratio of the fumed silica to methanol is 1-2 g: 200-500 mL; the ultrasonic mixing frequency is 40-50 kHz, and the ultrasonic mixing time is 30-60 min.

2. The method for preparing magnetic graphene nanocapsules according to claim 1, characterized in that, The purity of the methanol in the magnetic metal salt solution and the fumed silica solution is independently ≥ 99.8%.

3. The method for preparing magnetic graphene nanocapsules according to claim 1 or 2, characterized in that, In the step (1), the evaporation temperature is 50-60 ℃, and the evaporation rotation speed is 80-100 r / min.

4. The method for preparing magnetic graphene nanocapsules according to claim 3, characterized in that, In the step (1), the heat treatment is performed under the condition of a reducing gas, the flow rate of the reducing gas is 50-100 cfm; the heat treatment temperature is 810-900 ℃, the heat treatment time is 20-30 min, the temperature rising rate to the heat treatment temperature is 10-20 ℃ / min; the in-situ growth is performed in a methane atmosphere, the flow rate of the methane is 200-300 cfm, the in-situ growth temperature is 810-900 ℃, and the in-situ growth time is 5-10 min.

5. The method for preparing magnetic graphene nanocapsules according to claim 4, characterized in that, In the step (1), the product obtained by evaporation is ground before heat treatment.

6. The method of claim 1, 4 or 5, wherein the magnetic graphene nanocapsule is prepared by the following steps of: In the step (1), the molar volume ratio of the magnetic metal salt to the hydrofluoric acid solution in the step (2) is 0.0012 mol: 8-15 mL; the hydrofluoric acid solution is an aqueous hydrofluoric acid solution, and the volume concentration of the hydrofluoric acid solution is 10-20%.

7. The magnetic graphene nanocapsule prepared by the method of any one of claims 1-6.

8. The magnetic graphene nanocapsule of claim 7 in the preparation of a gastric magnetic thermal reagent.

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