Method for regulating and controlling polarization of macrophages

Abstract

The invention belongs to the technical field of nano biomedicine, and particularly relates to a method for regulating and controlling polarization of macrophages. Comprising the following steps: co-culturing ferrite nanoparticles and macrophages, so that the macrophages are polarized to M1 type; the ferrite nano-particles are MnFe2O4, CoFe2O4, ZnFe2O4 or MgFe2O4, and the ferrite nano-particles are MnFe2O4, CoFe2O4, wherein during co-culture, the mass of the ferrite nanoparticles is 20-400 [mu] g, and the concentration of the macrophages is 1 * 10 < 5 >-1 * 10 < 6 > cells / mL. According to the invention, ferrite nano-particles are used as experimental materials, and the polarization of macrophages is successfully induced by using the peroxidase-like activity of the nano-particles and metal ions carried by the nano-particles.

Description

Technical Field

[0001] The invention belongs to the technical field of nano-biomedicine, and in particular relates to a method for regulating macrophage polarization. Background Art

[0002] In the tumor microenvironment, macrophages are called tumor-associated macrophages (TAMs), which play an important role in the occurrence and development of tumors. TAMs are mainly M2 type, which can promote tumor growth and invasion. Thanks to the plasticity of macrophages, repolarizing M2 macrophages that promote tumor growth to M1 type that inhibits tumor growth has become an important strategy for tumor treatment. The rise of nanoscience has provided new means for regulating macrophage polarization. For example, iron-based nanomaterials have been widely explored for regulating macrophage polarization and are expected to be applied in the biomedical field. It has been reported that the efficiency of ferric oxide nanoparticles in polarizing M1 in vivo is higher than that of ferric oxide nanoparticles, and the reasons are attributed to two points: ① The inherent structure causes the iron ion release concentration of ferric oxide to be higher than that of ferric oxide, thereby producing more efficient activation of the IRF5 pathway and inhibition of the Arg-1 pathway; ② Fe2O4 has higher enzyme-like activity than Fe2O3 and can produce higher concentrations of reactive oxygen species. Similarly, Saeid Zanganeh conducted research on anti-tumor using Ferumoxytol and found that when nano-iron oxide particles were co-implanted with tumor cells, they could not only inhibit the growth of tumor cells, but also significantly increase the expression of macrophage CD80 (M1 macrophage marker) at the co-implantation site. These nanomaterials can affect the polarization direction of macrophages, thereby playing an important regulatory role in immune response. Advances in nanoscience have provided new possibilities for the use of macrophages as a treatment method, especially showing great potential in tumor immunotherapy. Through in-depth research and development, it is expected to bring revolutionary changes to future medical health.

[0003] However, due to the diversity of ferrite nanomaterials and the differences in the activity strength of peroxidase-like enzymes, the current method of using ferrite nanomaterials to efficiently induce macrophage polarization is still immature. Therefore, developing a universal method to regulate macrophage polarization has become an urgent and arduous task. Summary of the invention

[0004] To solve the above problems, the present invention provides a method for regulating macrophage polarization using ferrite nanoparticles.

[0005] This method uses ferrite nanoparticles for biological applications to affect the phenotypic changes of macrophages. This method can directly use nanoparticles to induce polarization of macrophages without using other agonist drugs, and has the advantages of high efficiency and low toxicity.

[0006] The implementation process of the present invention is as follows: A method for regulating macrophage polarization using ferrite nanoparticles, wherein the ferrite nanoparticles are co-cultured with macrophages to polarize the macrophages toward the M1 type; The ferrite nanoparticles are MnFe2O4, CoFe2O4, ZnFe2O4 or MgFe2O4; During co-culture, the mass of the ferrite nanoparticles is 20 μg to 400 μg, and the concentration of the macrophages is 1×10 5 ~1×10 6 cells / mL.

[0007] Preferably, the mass of the ferrite nanoparticles is any one of 30 μg, 50 μg, 80 μg, 100 μg, 120 μg, 150 μg, 200 μg, 300 μg and 400 μg.

[0008] Preferably, the co-cultivation time is 12 h to 48 h.

[0009] Preferably, the co-culture temperature is 36°C to 37°C.

[0010] Preferably, the co-culture contains CO2 at a volume concentration of 5% to 10%.

[0011] Preferably, the macrophages are selected from RAW264.7, J774A.1 or MH-S.

[0012] Preferably, the preparation method of the ferrite nanoparticles is: subjecting erucic acid iron and metal oleic acid complexes to dynamic synchronous thermal decomposition to obtain oil-phase ferrite particles, and modifying the oil-phase ferrite particles to remove the oil phase to obtain water-phase ferrite nanoparticles, i.e., ferrite nanoparticles; The mass ratio of the metal raw material to iron erucate in the metal oleic acid complex is 0.2-0.7:1.

[0013] Preferably, the oil-phase ferrite particles are modified with polyethylene glycol, polyacrylic acid, polyvinyl pyrrolidone, citric acid, 3-(3,4-dihydroxyphenyl)propionic acid or 2,3-dimercaptosuccinic acid.

[0014] Preferably, the ferrite nanoparticles have a morphology of sphere, tetrahedron, cube, octahedron or dodecahedron.

[0015] Preferably, the size of the ferrite nanoparticles is 2 nm to 40 nm.

[0016] Compared with the prior art, the present invention is beneficial in that: The present invention uses ferrite nanoparticles as experimental materials, utilizes the peroxidase-like activity of the nanoparticles and the metal ions they carry, and successfully induces macrophage polarization. The method of regulating macrophage polarization by nanoparticles provided by the present invention is simple to operate, does not require additional coating of polarization agonists, reduces production and time costs, and has universal applicability. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 A is the electron microscope image of manganese ferrite of Example 1 of the present invention, Figure 1 B is a statistical diagram of the particle size of manganese ferrite in Example 1 of the present invention, Figure 1 C is the Fourier transform infrared spectrum of the manganese ferrite before and after surface modification of Example 1 of the present invention, Figure 1 D is a flow cytometric graph of manganese ferrite-induced macrophage polarization in Example 1 of the present invention and marked with CD80 and CD86.

[0018] Figure 2 A is the electron microscope image of cobalt ferrite of Example 2 of the present invention, Figure 2 B is the cobalt ferrite particle size statistics of Example 2 of the present invention, Figure 2 C is the Fourier transform infrared spectrum of the cobalt ferrite before and after surface modification of Example 2 of the present invention, Figure 2 D is a flow cytometric graph of cobalt ferrite-induced macrophage polarization in Example 2 of the present invention and marked with CD80 and CD86.

[0019] Figure 3 A is the electron microscope image of zinc ferrite of Example 3 of the present invention, Figure 3 B is the zinc ferrite particle size statistics of Example 3 of the present invention, Figure 3 C is the Fourier transform infrared spectrum of zinc ferrite before and after surface modification of Example 3 of the present invention, Figure 3 D is a flow cytometric graph of zinc ferrite-induced macrophage polarization in Example 3 of the present invention and marked with CD80 and CD86.

[0020] Figure 4 A is the electron microscope image of magnesium ferrite of Example 4 of the present invention, Figure 4 B is the statistical diagram of the magnesium ferrite particle size of Example 4 of the present invention, Figure 4 C is the Fourier transform infrared spectrum of magnesium ferrite before and after surface modification of Example 4 of the present invention, Figure 4 D is a flow cytometric graph of magnesium ferrite-induced macrophage polarization in Example 4 of the present invention and marked with CD80 and CD86. DETAILED DESCRIPTION

[0021] The specific embodiments of the present invention are described in detail below, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention. The experimental methods described in the embodiments of the present invention are conventional methods unless otherwise specified.

[0022] Example 1 The method of inducing macrophage polarization by manganese ferrite comprises the following steps: First, accurately weigh 1.07 g of ferric erucate and 0.62 g of manganese oleate and place them in a 25 mL three-necked flask. Then, accurately add 0.64 mL of oleic acid, 1.9 mL of oleyl alcohol and 10 mL of benzyl ether, mix and pour into the flask. Put in a magnetic bar and adjust to stable rotation, and pass nitrogen protection. Slowly heat to 110℃ and stir at constant temperature for 30 min to eliminate water and oxygen. After that, heat to 265℃ at a rate of 5℃ / min and maintain this temperature and stir for 30 min. After the reaction is completed, immediately pour into a beaker containing cooled n-hexane for rapid cooling. Using anhydrous ethanol as an auxiliary agent, the mixture is centrifuged at 10000 r / min for 10 min in a centrifuge, repeated three times, and the oil phase ultra-small manganese ferrite nanoparticles are separated. Then, take 40 mg of oil phase ultra-small manganese ferrite particles, 100 mg of 3-(3,4-dihydroxyphenyl)propionic acid and 15 mL of tetrahydrofuran and add them to another 25 mL three-necked flask. Place in a constant temperature oil bath, add a magnet and pass nitrogen. Install a spherical condenser and pass water to prevent volatilization. Set the oil bath temperature to 50°C and stir at constant temperature for 5 h. After the reaction is completed, add the product to a centrifuge tube and add 1 mL of 0.5 M sodium hydroxide solution. Centrifuge at 10000 r / min for 10 min at 4°C. After centrifugation, add 2 mL of ultrapure water to finally obtain spherical aqueous manganese ferrite nanoparticles MnFe2O4 with a size of 3 nm, such as Figure 1 As shown in A and B.

[0023] After the oil phase ultrasmall manganese ferrite particles were modified with 3-(3,4-dihydroxyphenyl)propionic acid, the peak at 2920 cm -1 and 2850 cm -1 The characteristic peak of the alkane chain of the oleic acid molecule near the particle almost disappears, and the stretching vibration peak of the carboxyl group in the particle shifts, indicating that the alkane chain of oleic acid has been successfully replaced by 3-(3,4-dihydroxyphenyl) propionic acid and modified on the particle surface. Figure 1 As shown in C.

[0024] Disperse 20 mg of spherical aqueous manganese ferrite nanoparticles into 4 mL of 0.01 mol / L phosphate buffer at pH 7.4, place the particles in a sample bottle, loosen the lid, and place it in a high-pressure steam sterilizer, setting the sterilization time to 10 minutes. After sterilization, tighten the lid of the sample bottle, filter the particles using a 0.22 μM sterile filter membrane in a biological safety cabinet, and then conduct biological experiments.

[0025] Add 10 mL of fetal bovine serum to 40 mL of basal medium to prepare a complete medium with a serum content of 20%. 5 RAW264.7 cells at a concentration of 10 cells / mL were added to a 6-well plate. The nanoparticle concentration was diluted to 75 μg / mL using the prepared complete medium and added to the 6-well plate. 2 mL of medium was added to each well. The 6-well plate was placed in a cell culture incubator, set to 37°C, CO2 concentration 5%, and incubated for 24 h. After the incubation, the surface of the culture dish was washed three times with PBS, the cells were gently blown off, and the centrifuge was used at 1000 rpm for 3 min to collect the precipitate and use CD11b + 、CD80 + With CD86 + The antibody specifically stains macrophages.

[0026] The proportion of M1 cell polarization was detected by flow cytometry. Figure 1 As shown in D, MnFe2O4 induced 21.0% of M1 type (CD80 + CD86 + ) macrophages, and found that the proportion of M1 macrophages induced by nanoparticles was significantly higher than that in the control group, proving that nanoparticles have the ability to induce macrophage polarization.

[0027] Example 2 The method of inducing macrophage polarization by cobalt ferrite comprises the following steps: First, accurately weigh 1.07 g of ferric erucate and 0.62 g of cobalt oleate and place them in a 25 mL three-necked flask. Then, accurately add 0.64 mL of oleic acid, 1.9 mL of oleyl alcohol and 10 mL of benzyl ether, mix and pour into the flask. Add a magnetic bar and adjust to stable rotation, and pass nitrogen protection. Slowly heat to 110°C and stir at constant temperature for 30 min to eliminate water and oxygen. After that, heat to 265°C at a rate of 5°C / min and maintain this temperature and stir for 30 min. After the reaction is completed, immediately pour into a beaker containing cooled n-hexane for rapid cooling. Using anhydrous ethanol as an auxiliary agent, the mixture is centrifuged at 10000 r / min for 10 min in a centrifuge, repeated three times, and the oil phase ultra-small cobalt ferrite nanoparticles are separated. Then, take 40 mg of oil phase ultra-small cobalt ferrite particles, 100 mg of 3-(3,4-dihydroxyphenyl)propionic acid and 15 mL of tetrahydrofuran and add them to another 25 mL three-necked flask. Place in a constant temperature oil bath, add a magnet and pass nitrogen. Install a spherical condenser and pass water to prevent volatilization. Set the oil bath temperature to 50°C and stir at constant temperature for 5 h. After the reaction is completed, add the product to a centrifuge tube and add 1 mL of 0.5 M sodium hydroxide solution. Centrifuge at 10000 r / min for 10 min at 4°C. After centrifugation, add 2 mL of ultrapure water to finally obtain spherical aqueous cobalt ferrite nanoparticles CoFe2O4 with a size of 3 nm, such as Figure 2 As shown in A and B.

[0028] After the oil phase ultrasmall cobalt ferrite particles were modified with 3-(3,4-dihydroxyphenyl)propionic acid, the peak at 2920 cm -1 and 2850 cm -1 The characteristic peak of the alkane chain of the oleic acid molecule near the particle almost disappears, and the stretching vibration peak of the carboxyl group in the particle shifts, indicating that the alkane chain of oleic acid has been successfully replaced by 3-(3,4-dihydroxyphenyl) propionic acid and modified on the particle surface. Figure 2 As shown in C.

[0029] Disperse 20 mg of spherical aqueous cobalt ferrite nanoparticles into 4 mL of 0.01 mol / L phosphate buffer at pH 7.4, place the particles in a sample bottle, loosen the lid, and place it in a high-pressure steam sterilizer, setting the sterilization time to 10 minutes. After sterilization, tighten the lid of the sample bottle, filter the particles using a 0.22 μM sterile filter membrane in a biological safety cabinet, and then conduct biological experiments.

[0030] Add 10 mL of fetal bovine serum to 40 mL of basal medium to prepare a complete medium with a serum content of 20%. 5RAW264.7 cells at a concentration of 10 cells / mL were added to a 6-well plate. The nanoparticle concentration was diluted to 75 μg / mL using the prepared complete medium and added to the 6-well plate. 2 mL of medium was added to each well. The 6-well plate was placed in a cell culture incubator, set to 37°C, CO2 concentration 5%, and incubated for 24 h. After the incubation, the surface of the culture dish was washed three times with PBS, the cells were gently blown off, and the centrifuge was used at 1000 rpm for 3 min to collect the precipitate and use CD11b + 、CD80 + With CD86 + The antibody specifically stains macrophages.

[0031] The proportion of M1 cell polarization was detected by flow cytometry. Figure 2 As shown in D, CoFe2O4 induced 17.9% of M1 type (CD80 + CD86 + ) macrophages, and found that the proportion of M1 macrophages induced by nanoparticles was significantly higher than that in the control group, proving that nanoparticles have the ability to induce macrophage polarization.

[0032] Example 3 The method of inducing macrophage polarization by zinc ferrite comprises the following steps: First, accurately weigh 1.07 g of ferric erucate and 0.12 g of zinc carbonate and place them in a 25 mL three-necked flask. Then, accurately add 0.64 mL of oleic acid, 1.9 mL of oleyl alcohol and 10 mL of benzyl ether, mix and pour into the flask. Add a magnetic bar and adjust to stable rotation, and pass nitrogen protection. Slowly heat to 110°C and stir at constant temperature for 30 min to eliminate water and oxygen. After that, heat to 265°C at a rate of 5°C / min and maintain this temperature for 30 min. After the reaction is completed, immediately pour into a beaker containing cooled n-hexane for rapid cooling. Using anhydrous ethanol as an auxiliary agent, the mixture is centrifuged at 10000 r / min for 10 min in a centrifuge, repeated three times, and the oil phase zinc ferrite nanoparticles are separated. Then, take 40 mg of oil phase zinc ferrite particles, 100 mg of 3-(3,4-dihydroxyphenyl)propionic acid and 15 mL of tetrahydrofuran and add them to another 25 mL three-necked flask. Place in a constant temperature oil bath, add a magnet and pass nitrogen. Install a spherical condenser and pass water to prevent volatilization. Set the oil bath temperature to 50°C and stir at constant temperature for 5 h. After the reaction is completed, add the product to a centrifuge tube and add 1 mL of 0.5 M sodium hydroxide solution. Centrifuge at 10000 r / min for 10 min at 4°C. After centrifugation, add 2 mL of ultrapure water to finally obtain cubic aqueous zinc ferrite nanoparticles ZnFe2O4 with a size of 34 nm, such as Figure 3 As shown in A and B.

[0033] After the oil-phase zinc ferrite particles were modified with 3-(3,4-dihydroxyphenyl)propionic acid, the peak at 2920 cm -1 With 2850cm -1 The characteristic peak of the alkane chain of the oleic acid molecule near the particle almost disappears, and the stretching vibration peak of the carboxyl group in the particle shifts, indicating that the alkane chain of oleic acid has been successfully replaced by 3-(3,4-dihydroxyphenyl) propionic acid and modified on the particle surface. Figure 3 As shown in C.

[0034] Disperse 20 mg of cubic aqueous zinc ferrite nanoparticles into 4 mL of 0.01 mol / L phosphate buffer at pH 7.4, place the particles in a sample bottle, loosen the lid, and place it in a high-pressure steam sterilizer, setting the sterilization time to 10 minutes. After sterilization, tighten the lid of the sample bottle, filter the particles using a 0.22 μM sterile filter membrane in a biological safety cabinet, and then conduct biological experiments.

[0035] Add 10 mL of fetal bovine serum to 40 mL of basal medium to prepare a complete medium with a serum content of 20%. 5 RAW264.7 cells at a concentration of 10 cells / mL were added to a 6-well plate. The nanoparticle concentration was diluted to 75 μg / mL using the prepared complete medium and added to the 6-well plate. 2 mL of medium was added to each well. The 6-well plate was placed in a cell culture incubator, set to 37°C, CO2 concentration 5%, and incubated for 24 h. After the incubation, the surface of the culture dish was washed three times with PBS, the cells were gently blown off, and the centrifuge was used at 1000 rpm for 3 min to collect the precipitate and use CD11b + 、CD80 + With CD86 + The antibody specifically stains macrophages.

[0036] The proportion of M1 cell polarization was detected by flow cytometry. Figure 3 As shown in D, ZnFe2O4 induced 14.1% of M1 type (CD80 + CD86 + ) macrophages, and found that the proportion of M1 macrophages induced by nanoparticles was significantly higher than that in the control group, proving that nanoparticles have the ability to induce macrophage polarization.

[0037] Example 4 The method for inducing macrophage polarization by magnesium ferrite comprises the following steps: First, accurately weigh 1.07 g of ferric erucate, 0.296 g of magnesium oleate, 0.57 g of oleic acid, 0.54 g of oleylamine, 1.61 g of oleyl alcohol and 10 mL of benzyl ether, mix and pour into a 25 mL three-necked flask. Add a magnet and adjust to stable rotation, and pass nitrogen protection. Slowly heat to 110 ° C and stir at constant temperature for 30 min to eliminate water and oxygen. After that, heat to 250 ° C at a rate of 5 ° C / min, maintain this temperature and stir for 20 min. After the reaction is completed, immediately pour into a beaker containing cooled n-hexane for rapid cooling. Using anhydrous ethanol as an auxiliary agent, the mixture is centrifuged at 10000 r / min in a centrifuge for 10 min, repeated three times, and the ultra-small magnesium ferrite nanoparticles in the oil phase are separated. Next, take 40 mg of oil-phase ultra-small magnesium ferrite particles, 100 mg of 3-(3,4-dihydroxyphenyl)propionic acid and 15 mL of tetrahydrofuran and add them to another 25 mL three-necked flask. Place it in a constant temperature oil bath, add a magnet and pass nitrogen. Install a spherical condenser and pass water to prevent volatilization. Set the oil bath temperature to 50°C and stir at a constant temperature for 5 h. After the reaction is completed, add the product to a centrifuge tube, add 1 mL of 0.5 M sodium hydroxide solution, and centrifuge at 10000 r / min for 10 min at 4°C. After centrifugation, add 2 mL of ultrapure water to finally obtain spherical aqueous phase magnesium ferrite nanoparticles MgFe2O4 with a size of 3 nm, such as Figure 4 As shown in A and B.

[0038] After the oil phase ultra-small magnesium ferrite particles were modified with 3-(3,4-dihydroxyphenyl) propionic acid, the peak at 2920 cm -1 and 2850 cm -1 The characteristic peak of the alkane chain of the oleic acid molecule near the particle almost disappears, and the stretching vibration peak of the carboxyl group in the particle shifts, indicating that the alkane chain of oleic acid has been successfully replaced by 3-(3,4-dihydroxyphenyl) propionic acid and modified on the particle surface. Figure 4 As shown in C.

[0039] Disperse 20 mg of spherical aqueous magnesium ferrite nanoparticles into 4 mL of 0.01 mol / L phosphate buffer at pH 7.4, place the particles in a sample bottle, loosen the lid, and place it in a high-pressure steam sterilizer, setting the sterilization time to 10 minutes. After sterilization, tighten the lid of the sample bottle, filter the particles using a 0.22 μM sterile filter membrane in a biological safety cabinet, and then conduct biological experiments.

[0040] Add 10 mL of fetal bovine serum to 40 mL of basal medium to prepare a complete medium with a serum content of 20%. 5RAW264.7 cells at a concentration of 10 cells / mL were added to a 6-well plate. The nanoparticle concentration was diluted to 75 μg / mL using the prepared complete medium and added to the 6-well plate. 2 mL of medium was added to each well. The 6-well plate was placed in a cell culture incubator, set to 37°C, CO2 concentration 5%, and incubated for 24 h. After the incubation, the surface of the culture dish was washed three times with PBS, the cells were gently blown off, and the centrifuge was used at 1000 rpm for 3 min to collect the precipitate and use CD11b + 、CD80 + With CD86 + The antibody specifically stains macrophages.

[0041] The proportion of M1 cell polarization was detected by flow cytometry. Figure 4 As shown in D, MgFe2O4 induced 14.0% of M1 type (CD80 + CD86 + ) macrophages, and found that the proportion of M1 macrophages induced by nanoparticles was significantly higher than that in the control group, proving that nanoparticles have the ability to induce macrophage polarization.

[0042] It should be noted that when the claims of the present invention involve numerical ranges, it should be understood that the two endpoints of each numerical range and any numerical value between the two endpoints can be selected. In order to avoid redundancy, the present invention describes a preferred embodiment.

[0043] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0044] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for regulating macrophage polarization, characterized in that: The following steps are involved: Co-culture of ferrite nanoparticles with macrophages polarized the macrophages toward the M1 type; The ferrite nanoparticles are MnFe2O4, CoFe2O4, ZnFe2O4 or MgFe2O4; During co-culture, the mass of the ferrite nanoparticles is 20 μg to 400 μg, and the concentration of the macrophages is 1×10 5 ~1×10 6 cells / mL.

2. The method according to claim 1, characterized in that The co-cultivation time is 12 h to 48 h.

3. The method according to claim 1, characterized in that: The co-cultivation temperature is 36°C to 37°C.

4. The method according to claim 1, characterized in that: During the co-culture, the volume concentration of CO2 is 5% to 10%.

5. The method according to claim 1, characterized in that The macrophages are selected from RAW264.7, J774A.1 or MH-S.

6. The method according to claim 1, characterized in that The preparation method of the ferrite nanoparticles is as follows: ferric erucate and metal oleic acid complexes are subjected to dynamic synchronous thermal decomposition to obtain oil-phase ferrite particles, and the oil-phase ferrite particles are modified to remove the oil phase to obtain water-phase ferrite nanoparticles, i.e., ferrite nanoparticles; The mass ratio of the metal raw material to iron erucate in the metal oleic acid complex is 0.2-0.7:

1.

7. The method according to claim 6, characterized in that The oil-phase ferrite particles were modified with polyethylene glycol, polyacrylic acid, polyvinyl pyrrolidone, citric acid, 3-(3,4-dihydroxyphenyl)propionic acid or 2,3-dimercaptosuccinic acid.

8. The method according to claim 1, characterized in that The ferrite nanoparticles have a morphology of sphere, tetrahedron, cube, octahedron or dodecahedron.

9. The method according to claim 1, characterized in that: The size of the ferrite nanoparticles is 2 nm to 40 nm.

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