A kind of manganese-zinc ferrite nanoparticles, magnetic polystyrene composite microspheres prepared therefrom and applications thereof

Abstract

The present invention belongs to the technical field of polystyrene composite microspheres, and discloses a manganese-zinc ferrite nanoparticle, a magnetic polystyrene composite microsphere prepared therefrom, and an application thereof. The nanoscale magnetic polystyrene composite microsphere can significantly reduce its size and improve its magnetic properties, and is particularly suitable for biomedical fields such as nuclear magnetic resonance, immunoassay, and nucleic acid hybridization involving the study of imaging performance. By combining raw materials including metal compounds, surfactants, emulsifiers, initiators, and methacrylic acid in the overall preparation process, and selecting the above-mentioned preparation raw materials for matching, the prepared nanoscale magnetic polystyrene microspheres with a core-shell structure have the characteristics of adjustable particle size and excellent monodispersity, and can be used as a contrast agent for magnetic resonance imaging, having excellent imaging performance.

Description

Technical Field

[0001] The present invention relates to the technical field of polystyrene composite microspheres, and particularly relates to a manganese-zinc ferrite nanoparticle, a magnetic polystyrene composite microsphere prepared therefrom, and an application thereof. Background Art

[0002] Magnetic polymer microspheres are a composite material combining a magnetic material and a polymer microsphere. Due to their characteristics such as being able to be rapidly separated in an external magnetic field and having surfaces that can be modified to carry amino groups, carboxyl groups, epoxy groups, etc., magnetic polymer microspheres can be widely applied in biomedical fields such as immobilized enzymes, targeted drug carriers, cell separation, nuclear magnetic resonance, immunoassay, nucleic acid hybridization, etc. Currently, magnetic polystyrene microspheres are the most commonly used magnetic polymer microspheres, and their magnetic particles usually choose Fe3O4 because of its simple preparation process, stable properties, strong magnetic responsiveness, high particle purity, and the fact that ferrofluids will not cause human poisoning after being injected into the body, thus becoming the preferred material for the magnetic cores of magnetic polymer microspheres.

[0003] A commonly used method for preparing magnetic polystyrene microspheres is to coat Fe3O4 nanoparticles on the prepared polystyrene microspheres through a coprecipitation method, and finally complete magnetization. For example, CN105467112A and CN1631949A. The advantages are simple process and short preparation time, but there are several disadvantages in the preparation of magnetic polystyrene microspheres: the overall magnetic content of the microspheres is low, and the magnetic response to an external magnetic field is correspondingly low, resulting in the problem that magnetic microspheres are difficult to rapidly enrich in biological applications such as chemiluminescence detection; in addition, the magnetic particle sizes in the coprecipitation method are not uniform, and when coated on the surface of the microspheres, it may cause the microsphere particle size and magnetic content distribution to become wider.

[0004] In particular, when magnetic polystyrene microspheres are used as magnetic resonance detection materials, the magnetic particle loading of the microspheres with Fe3O4 nanoparticles as the coating material is relatively large, which will change the physicochemical properties of the polystyrene microspheres and affect the evaluation of the harmfulness of polystyrene itself to organisms. If the magnetic particle content is too small, it will affect the imaging effect of magnetic resonance detection. In addition, current related research mainly focuses on micron-sized polystyrene, and the micron-sized dimensions are difficult to enter human tissue cells, thus causing toxic effects. Summary of the Invention

[0005] The purpose of the present invention is to solve the application limitations of polystyrene microspheres coated with Fe3O4 magnetic nanoparticles, and to propose a manganese-zinc ferrite nanoparticle, a magnetic polystyrene composite microsphere prepared therefrom, and an application thereof. The core-shell structured nano-sized magnetic polystyrene composite microspheres can significantly reduce their size and improve their magnetic properties, and are particularly suitable for biomedical fields such as nuclear magnetic resonance, immunoassay, nucleic acid hybridization, etc. involving research on imaging performance.

[0006] The technical solution of the present invention is as follows: A kind of manganese-zinc ferrite nanoparticles, and the preparation process is as follows: Decompose the metal complex precursor in a high-boiling-point solvent, and at the same time add a surfactant to obtain manganese-zinc ferrite nanoparticles with controllable orientation.

[0007] The metal complex precursor is iron acetylacetonate, manganese acetylacetonate and zinc acetylacetonate; the high-boiling-point solvent is dibenzyl ether; the surfactant is a mixed solution of oleic acid and oleylamine.

[0008] The preparation steps of the manganese-zinc ferrite nanoparticles are as follows:

[0009] Step 1: Weigh iron acetylacetonate, manganese acetylacetonate and zinc acetylacetonate according to a molar ratio of 10:3:2, add dibenzyl ether with a molar ratio of 1:60 to iron acetylacetonate and stir to obtain a metal solution;

[0010] Step 2: Add a surfactant with a molar ratio of 10:1 to dibenzyl ether to the metal solution, wherein the molar ratio of oleic acid to oleylamine is 8:4 to 11:1, heat to 90 - 120 °C, and continuously stir for 60 - 90 minutes;

[0011] Step 3: Place the solution obtained in Step 2 in a programmable temperature-controlled heating device, heat it to the nucleation temperature of 200 - 220 °C at a certain heating rate, and keep it at this nucleation temperature for 90 - 120 minutes;

[0012] Step 4: Further raise the temperature of the product obtained in Step 3 to the particle growth temperature of 280 - 300 °C, and keep it at this temperature for 60 - 90 minutes, and then the solution is naturally cooled;

[0013] Step 5: Centrifuge the solution obtained in Step 4 to obtain manganese-zinc ferrite nanoparticles.

[0014] The heating rate is 3 - 6 °C / min.

[0015] The centrifugation treatment in Step 5 is to use ethanol as a detergent and centrifuge at a speed of 3 min / 10000 r. After centrifugation, manganese-zinc ferrite nanoparticles are obtained.

[0016] A magnetic polystyrene composite microsphere prepared from manganese-zinc ferrite nanoparticles. The manganese-zinc ferrite nanoparticles are dissolved in an alcohol solvent, and at the same time, styrene, an emulsifier and an initiator are added. Argon is introduced and stirred at 50 - 80 °C to obtain a core-shell structured nano-scale magnetic polystyrene composite microsphere.

[0017] The alcohol solvent is n-hexane; the emulsifier is sodium dodecyl sulfate or methacrylic acid; the initiator is potassium persulfate.

[0018] The specific steps for preparing magnetic polystyrene composite microspheres prepared from manganese-zinc ferrite nanoparticles are as follows:

[0019] Step 1: Add 0.2 g of manganese-zinc ferrite nanoparticles to 1 ml of n-hexane and dissolve them by ultrasonic treatment to obtain a manganese-zinc ferrite solution;

[0020] Step 2: Prepare a sodium dodecyl sulfate solution with a concentration of 1.5 - 2.5 mg / mL; drop the manganese-zinc ferrite solution into the sodium dodecyl sulfate solution at 20 - 25 °C. The volume ratio of the manganese-zinc ferrite solution to the sodium dodecyl sulfate solution is 1:20, and ultrasonic treatment is carried out at this temperature for 10 - 30 min;

[0021] Step 3: Weigh styrene. The volume ratio of styrene to the volume of the solution after ultrasonic treatment in Step 2 is 1:20; drop styrene into the solution after ultrasonic treatment and carry out ultrasonic treatment at 20 - 25 °C to obtain a mixed solution; introduce argon gas into the mixed solution and stir at 50 - 80 °C;

[0022] Step 4: Prepare a potassium persulfate solution with a concentration of 40 - 80 mg / mL. The volume ratio of the potassium persulfate solution to the mixed solution obtained in Step 3 is 1:40, add it to the mixed solution obtained in Step 3, and introduce argon gas and stir at 50 - 80 °C for 20 - 50 min;

[0023] Step 5: Add methacrylic acid to the solution obtained in Step 4. For every 0.2 g of manganese-zinc ferrite, 0.5 - 1.5 ml of methacrylic acid is added, and keep it at 50 - 80 °C for 12 - 24 h, then cool it to room temperature; carry out centrifugation treatment and dry it at a certain temperature to obtain core-shell structured nano-scale magnetic polystyrene composite microspheres.

[0024] The centrifugation treatment in Step 5 is to use ethanol as a detergent, centrifuge at 10000 r / 5 min, and dry at 60 °C.

[0025] An application of the core-shell structured nano-scale magnetic polystyrene composite microspheres, used as a nuclear magnetic resonance contrast agent.

[0026] The beneficial effects of the present invention: The present invention provides a manganese-zinc ferrite nanoparticle, the magnetic polystyrene composite microspheres prepared therefrom and their applications. By controlling the proportion of surfactants, nucleation temperature and growth temperature during the preparation process of manganese-zinc ferrite particles, the morphology and size of the prepared manganese-zinc ferrite particles can be controlled; through the combination of manganese-zinc ferrite particles, emulsifier, initiator and methacrylic acid during the preparation process of magnetic polystyrene composite microspheres, and by selecting the above-mentioned preparation raw materials for combination, the prepared core-shell structured nano-scale magnetic polystyrene microspheres have the characteristics of adjustable particle size and excellent monodispersity, can be used as a contrast agent for nuclear magnetic resonance imaging, and have excellent imaging performance. Description of the Drawings

[0027] Figure 1 Electron micrograph of the coating material manganese zinc ferrite provided for Example 1.

[0028] Figure 2 Particle size distribution diagram of the coating material manganese zinc ferrite provided for Example 1.

[0029] Figure 3 Electron micrograph of the core-shell structured nano-sized magnetic polystyrene microspheres provided for Example 2.

[0030] Figure 4 Particle size distribution diagram of the core-shell structured nano-sized magnetic polystyrene microspheres provided for Example 2. Detailed implementation manners

[0031] The present invention will be further described below by combining the accompanying drawings and specific embodiments. The embodiments of the present invention are intended to enable those skilled in the art to better understand the present invention and do not impose any limitations on the present invention. The working process and working principle of the present invention will be further described below with a preferred embodiment of the present invention.

[0032] Example 1: Preparation of coating material manganese zinc ferrite nanoparticles;

[0033] Step 1: Weigh 0.353 g (1 mmol) of iron acetylacetonate; 0.106 g (0.3 mmol) of manganese acetylacetonate; 0.053 g (0.2 mmol) of zinc acetylacetonate.

[0034] Step 2: Place the iron acetylacetonate, manganese acetylacetonate, and zinc acetylacetonate weighed in Step 1 into a 100 ml three-necked flask, add 10 ml of dibenzyl ether, and stir for 30 minutes.

[0035] Step 3: Add a surfactant to the metal solution obtained in Step 2, with an addition amount of 6 mmol, where the ratio of oleic acid to oleylamine is 11:1, heat to 120 °C, and continuously stir for 60 minutes.

[0036] Step 4: Place the solution obtained in Step 3 into a programmable temperature-controlled heating device, heat it to the nucleation temperature of 220 °C at a rate of 5 °C / min, and keep it at this temperature for 2 hours.

[0037] Step 5: Further raise the temperature of the product obtained in Step 4 to 280 °C, and keep it at this temperature for 1 hour, and then let the solution cool naturally.

[0038] Step 6: Centrifuge the product obtained in Step 5, use ethanol as the detergent, centrifuge at a speed of 3 min / 10000 r, and obtain manganese zinc ferrite nanoparticles after centrifugation is completed.

[0039] Example 2

[0040] The difference between this comparative example and Example 1 lies in that the ratio of oleic acid to oleylamine in Step 3 is 8:4.

[0041] Comparative Example 1:

[0042] The difference between this comparative example and Example 1 lies in that the ratio of oleic acid to oleylamine in Step 3 is 6:6.

[0043] Comparative Example 2:

[0044] The difference between this comparative example and Example 1 lies in that the nucleation temperature in Step 4 is 240 °C.

[0045] Comparative Example 3:

[0046] The difference between this comparative example and Example 1 lies in that the particle growth temperature in Step 5 is 320 °C.

[0047] The particle sizes of Example 1, Example 2, Comparative Example 1, Comparative Example 2, and Comparative Example 3 are shown in Table 1 below.

[0048] Table 1 Particle Sizes of Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 3

[0049]

[0050]

[0051] It can be seen from the experimental data in Table 1 that after preparing the coated material manganese-zinc ferrite nanoparticles according to the present invention, the size of the manganese-zinc ferrite nanoparticles is reduced by 73.32%, 72.43%, and 71.70% respectively compared with the case where the ratio of oleic acid to oleylamine is the same (Comparative Example 1), the nucleation temperature is higher (Comparative Example 2), and the particle growth temperature is higher (Comparative Example 3). The manganese-zinc ferrite nanoparticles prepared by the present invention are the smallest, so when used as a coating material, the coating amount is larger, and the loading amount is also larger under the same conditions. Through Figure 1 the electron microscopy images, it can be seen that the prepared manganese-zinc ferrite particles are spherical and have good overall dispersibility.

[0052] Example 3: Preparation of Core-Shell Structured Nanoscale Magnetic Polystyrene Microspheres;

[0053] Step 1: Preparation of the coating material manganese-zinc ferrite nanoparticles: In this experiment, the coating material manganese-zinc ferrite nanoparticles were prepared by the method of high-temperature thermal decomposition. First, weigh 0.353 g (1 mmol) of iron acetylacetonate; 0.106 g (0.3 mmol) of manganese acetylacetonate; 0.053 g (0.2 mmol) of zinc acetylacetonate. Then, place the weighed iron acetylacetonate, manganese acetylacetonate and zinc acetylacetonate in a 100-ml three-necked flask, add 10 ml of dibenzyl ether and stir for 30 minutes. After that, add a surfactant to the solution, with an addition amount of 6 mmol, where the ratio of oleic acid to oleylamine is 11:1, heat to 120 °C and continue stirring for 60 minutes. Place the obtained solution in a programmable temperature-controlled heating device, heat it to the nucleation temperature of 220 °C at a rate of 5 °C / min, and keep it at this temperature for 2 hours. Then further raise the temperature of the product to 280 °C and maintain it at this temperature for 1 hour, and then let the solution cool naturally. Finally, centrifuge the obtained product, use ethanol as the detergent, centrifuge at a speed of 3 min / 10,000 r, and obtain manganese-zinc ferrite nanoparticles after centrifugation is completed.

[0054] Step 2: Add 0.2 g of the manganese-zinc ferrite nanoparticles obtained by centrifugation in Step 1 to 1 ml of n-hexane and ultrasonicate for 5 min to dissolve the manganese-zinc ferrite nanoparticles.

[0055] Step 3: Weigh 0.04 g of sodium dodecyl sulfate and dissolve it in 20 ml of deionized water, and ultrasonicate for 5 min.

[0056] Step 4: Drop the solution obtained in Step 2 into the aqueous sodium dodecyl sulfate solution obtained in Step 3 at 23 °C, and ultrasonicate for 30 min at this temperature.

[0057] Step 5: Drop 1.05 ml of styrene into the solution obtained in Step 4 and ultrasonicate for 30 min at 23 °C.

[0058] Step 6: Pour the mixed solution after ultrasonication in Step 5 into a three-necked flask, introduce argon for 30 min to remove the air in the flask.

[0059] Step 7: Weigh 0.02 g of potassium persulfate and dissolve it in 0.5 ml of deionized water.

[0060] Step 8: Add the potassium persulfate solution obtained in Step 7 to the solution obtained in Step 6, and the volume ratio of the potassium persulfate solution to the solution obtained in Step 6 is 1:40, and stir at 75 °C for 30 min.

[0061] Step 9: Add 1 ml of methacrylic acid to the solution obtained in Step 8, keep it at 75 °C for 18 h, and then cool to room temperature.

[0062] Step 10: Use ethanol as the detergent for the product obtained in Step 9, centrifuge at 10000 r / 5 min, and dry at 60 °C.

[0063] Comparative Example 4:

[0064] The difference between this comparative example and Example 3 is that the mass of sodium dodecyl sulfate weighed in Step 3 is 0.02 g.

[0065] Comparative Example 5:

[0066] The difference between this comparative example and Example 3 is that the mass of potassium persulfate weighed in Step 7 is 0.01 g.

[0067] Comparative Example 6:

[0068] The difference between this comparative example and Example 3 is that the amount of methacrylic acid weighed in Step 9 is 2 ml.

[0069] The particle sizes of the magnetic polystyrene in Example 3, Comparative Example 4, Comparative Example 5, and Comparative Example 6 are shown in Table 2 below.

[0070] Table 2 Particle Sizes of Magnetic Polystyrene in Example 3, Comparative Example 4, Comparative Example 5, and Comparative Example 6

[0071] Case number Particle size (nm) Example 3 267.11 Comparative Example 4 509.68 Comparative Example 5 490.31 Comparative Example 6 495.82

[0072] It can be seen from the experimental data in Table 2 that after preparing the nano-scale magnetic polystyrene microspheres with the core-shell structure of the present invention, compared with different emulsifier contents (Comparative Example 4), different initiator contents (Comparative Example 5), and different methacrylic acid contents (Comparative Example 6), the particle size of the magnetic polystyrene is only 267.11 nm, and through Figure 3 the electron microscope images, it can be seen that the magnetic polystyrene particles have good dispersion, and the manganese-zinc ferrite nanoparticles are completely coated. With small particle size and good coating effect, it can be used as a reagent such as a contrast agent in the medical field.

[0073] The present invention uses the above embodiments to illustrate a manganese-zinc ferrite nanoparticle, the magnetic polystyrene composite microspheres prepared therefrom, and their applications. However, the present invention is not limited to the above embodiments, that is, it does not mean that the present invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvement to the present invention, the equivalent replacement of the raw materials of the products of the present invention, the addition of auxiliary components, and the selection of specific methods, etc., all fall within the protection scope and the disclosure scope of the present invention.

Claims

1. A magnetic polystyrene composite microsphere for preparing manganese-zinc ferrite nanoparticles, characterized in that, The specific steps are as follows: Step 1: Add 0.2 g of manganese-zinc ferrite nanoparticles to 1 ml of n-hexane and dissolve them by ultrasonic treatment to obtain a manganese-zinc ferrite solution; Step 2: Prepare a sodium dodecyl sulfate solution with a concentration of 1.5 - 2.5 mg / mL; drop the manganese-zinc ferrite solution into the sodium dodecyl sulfate solution at 20 - 25 °C, with a volume ratio of the manganese-zinc ferrite solution to the sodium dodecyl sulfate solution of 1:20, and perform ultrasonic treatment for 10 - 30 min at this temperature; Step 3: Weigh styrene, with a volume ratio of styrene to the volume of the solution after ultrasonic treatment in Step 2 of 1:20; drop styrene into the solution after ultrasonic treatment and perform ultrasonic treatment at 20 - 25 °C to obtain a mixed solution; introduce argon gas into the mixed solution and stir at 50 - 80 °C; Step 4: Prepare a potassium persulfate solution with a concentration of 40 - 80 mg / mL, with a volume ratio of the potassium persulfate solution to the mixed solution obtained in Step 3 of 1:40, add it to the mixed solution obtained in Step 3, and introduce argon gas and stir at 50 - 80 °C for 20 - 50 min; Step 5: Add methacrylic acid to the solution obtained in Step 4, with 0.5 - 1.5 ml of methacrylic acid corresponding to every 0.2 g of manganese-zinc ferrite, and keep it at 50 - 80 °C for 12 - 24 h, then cool it to room temperature; perform centrifugation and dry it at a certain temperature to obtain core-shell structured nano-sized magnetic polystyrene composite microspheres.

2. The magnetic polystyrene composite microspheres prepared from the manganese-zinc ferrite nanoparticles according to claim 1, characterized in that, The preparation process of the manganese-zinc ferrite nanoparticles is as follows: Decompose the metal complex precursor in a high-boiling-point solvent, and at the same time add a surfactant to obtain manganese-zinc ferrite nanoparticles with controllable orientation.

3. The magnetic polystyrene composite microspheres prepared from the manganese-zinc ferrite nanoparticles according to claim 2, wherein, The metal complex precursor is iron acetylacetonate, manganese acetylacetonate, and zinc acetylacetonate; the high-boiling-point solvent is dibenzyl ether; the surfactant is a mixed solution of oleic acid and oleylamine.

4. The magnetic polystyrene composite microspheres prepared from the manganese-zinc ferrite nanoparticles according to claim 1, wherein, The preparation steps of the manganese-zinc ferrite nanoparticles are as follows: Step 1: Weigh iron acetylacetonate, manganese acetylacetonate, and zinc acetylacetonate according to a molar ratio of 10:3:2, add dibenzyl ether with a molar ratio to iron acetylacetonate of 1:60 and stir to obtain a metal solution; Step 2: Add a surfactant with a molar ratio to dibenzyl ether of 10:1 to the metal solution, where the molar ratio of oleic acid to oleylamine is 8:4 - 11:1, heat to 90 - 120 °C, and continuously stir for 60 - 90 minutes; Step 3: Place the solution obtained in Step 2 in a programmable temperature-controlled heating device, heat it to the nucleation temperature of 200 - 220 °C at a certain heating rate, and keep it at this nucleation temperature for 90 - 120 minutes; Step 4: Further raise the temperature of the product obtained in Step 3 to the particle growth temperature of 280 - 300 °C, and keep it at this temperature for 60 - 90 minutes, and then let the solution cool naturally; Step 5: Centrifuge the solution obtained in Step 4 to obtain manganese-zinc ferrite nanoparticles.

5. The magnetic polystyrene composite microspheres prepared from the manganese-zinc ferrite nanoparticles according to claim 4, characterized in that, The heating rate is 3 - 6 °C / min.

6. The magnetic polystyrene composite microspheres prepared from the manganese-zinc ferrite nanoparticles according to claim 5, wherein, The centrifugation treatment in Step 5 is to use ethanol as a detergent and centrifuge at a speed of 3 min / 10000 r. After centrifugation, manganese-zinc ferrite nanoparticles are obtained.

7. The magnetic polystyrene composite microspheres prepared from the manganese zinc ferrite nanoparticles according to claim 1, characterized in that, The centrifugation treatment in step 5 is as follows: using ethanol as the detergent, centrifuging at 10,000 r / 5 min and drying at 60 °C.

8. Application of a core-shell structured nano-sized magnetic polystyrene composite microsphere, characterized in that, The nanoscale magnetic polystyrene composite microspheres with a core-shell structure are the magnetic polystyrene composite microspheres described in any one of claims 1-7 and are used as magnetic resonance imaging contrast agents.

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