A method for preparing magnetic amorphous metal nanomaterial

Abstract

The present invention discloses a method for preparing a magnetic amorphous metal nanomaterial. The method comprises the following steps: adding a metal citrate and a polyoxyethylene polyoxypropylene ether triblock copolymer, polyethylene glycol, polyvinyl pyrrolidone and other surfactants to an aqueous phase system, stirring magnetically and heating the mixture to fully dissolve the mixture, thereby obtaining a mixed solution A; dissolving a reducing agent such as sodium borohydride in the aqueous phase to obtain a solution B; slowly dripping the B solution into the A solution, and after the dripping is complete, dripping ethanol to obtain a mixed solution C, which is sequentially subjected to ethanol dispersion and centrifugal precipitation operations, and repeated three times to obtain a surface amorphous nanometal material. The present invention prepares a variety of magnetic amorphous metal nanomaterials with uniform particle size on a large scale through a simple and environmentally friendly one-step reduction method using an aqueous solution. These materials have a significant warming effect under magnetic field or near-infrared light irradiation, and can effectively scavenge oxidative components such as reactive oxygen free radicals (ROS), and are used in the treatment of inflammatory diseases such as joint inflammation.

Description

Technical Field

[0001] The present invention belongs to the technical field of magnetic amorphous metal nanomaterials, and specifically relates to a method for preparing amorphous iron, cobalt and nickel metal nanoparticles and their application in biomedical fields such as the treatment of inflammatory diseases. Background Art

[0002] Amorphous nanometallic materials are a special type of metallic nanomaterials. Their microscopic manifestations are long-range disorder in atomic arrangement. They are condensed matter composed of disordered atomic stacking, with structural and dynamic inhomogeneities at the nano and micro scales. Compared with conventional crystalline nanometallic materials, amorphous materials have unique and excellent physical, mechanical and chemical properties. For example, amorphous iron-based metal materials have good magnetic conductivity and can replace traditional silicon steel to make transformer cores, greatly improving transformer efficiency. Among them, magnetic amorphous nanomaterials are a class of metal materials with excellent soft magnetic properties, mainly including amorphous iron, cobalt, nickel, etc. Due to their good biocompatibility, biodegradability and high strength, they are widely used in the biomedical field. For example, amorphous nickel-based materials have good biocompatibility, biodegradability and do not cause allergic reactions. They can be used in medicine to repair implants and manufacture artificial bones or teeth. Recent studies have shown that amorphous nanometal materials have good therapeutic effects in inflammatory-related diseases such as atherosclerosis, ulcerative colitis, and osteoarthritis. They can be used as an innovative treatment for inflammatory diseases and have huge market application potential in the field of medical and health care.

[0003] Although the application of amorphous metal nanomaterials has made great progress in the past few decades, their industrial or clinical application still faces bottlenecks. The main problem is how to use simple and easy methods to prepare amorphous metal nanomaterials with uniform morphology and particle size on a large scale. In particular, for magnetic amorphous materials, the magnetic interaction between particles often causes the particles to agglomerate during the preparation process, greatly affecting the uniformity and stability of the final product quality. It is well known that the formation of amorphous metal nanomaterials mainly relies on controlling the nucleation and growth of the crystalline phase, so that the particles do not transform into a crystalline state with changes in temperature, pressure and density, but instead form a metastable, non-equilibrium amorphous state. At present, the preparation methods of amorphous metal materials mainly include vacuum evaporation, sputtering, glow discharge, chilling and chemical vapor deposition. Patent CN201910383717.1 reports a method for preparing amorphous bismuth ferrite nanomaterials. This method is a "top-down" synthesis method. Iron oxide and bismuth oxide are used as raw materials. The raw materials are ball-milled by mechanical alloying to obtain amorphous bismuth ferrite. Then, the amorphous bismuth ferrite is precipitated into a pure bismuth ferrite nanocrystalline structure by high-temperature heat treatment. The amorphous material prepared by this method has extremely uneven particle size distribution and irregular morphology. It does not have dispersibility in aqueous solutions and cannot be applied in the biomedical field. Patent CN201910991191.5 reports a method for preparing a graphene nanosheet / amorphous iron-based composite coating. First, the composite powder used for plasma spraying is prepared by planetary ball milling and PVA solution granulation. Then, the wear-resistant and anti-corrosion coating is prepared under the action of plasma spraying. This method places high demands on the dispersion of intermediate particles and the control of reaction conditions, resulting in poor experimental reproducibility. Patent CN201810154882.5 reports a method for preparing amorphous nanomaterials. This method first modifies the surface of iron powder and then uses high-energy ball milling to prepare a core-shell iron / ferrite composite powder. This is also a "top-down" synthesis method. The prepared material has poor stability and is prone to inter-particle agglomeration during the preparation process, which is not conducive to practical application. Furthermore, the preparation and application of amorphous metal nanomaterials are mostly used for coating certain materials, and there are almost no reports on their application in the biomedical field.

[0004] In summary, the preparation process of magnetic amorphous metal nanomaterials is relatively complex, with too many parameters requiring control during each step. The product's morphology and particle size are non-uniform, making aqueous dispersion nearly impossible and thus unsuitable for biomedical applications. The product's low yield leads to high preparation costs, and the materials also suffer from a series of issues, including poor structural stability and limited application. Therefore, it is crucial to develop a simple and efficient method for the large-scale preparation of magnetic amorphous metal nanomaterials with uniform size and morphology, high stability, and good dispersibility, and to expand their application in the biomedical field. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a method for preparing a magnetic amorphous nanometal material in view of the above-mentioned deficiencies in the prior art.

[0006] In order to solve the above technical problems, the technical solution adopted by the present invention is: a method for preparing magnetic amorphous metal nanomaterials, the method comprising:

[0007] A1. Add the surfactant to 100 mL of deionized water, stir to mix, introduce protective gas, raise the temperature to 50°C to 70°C, keep warm for 0.5 to 2.0 hours, and drain all water and oxygen from the system;

[0008] A2, add the metal salt of citric acid to A1, stir and disperse, and continue to keep warm for 0.5 to 1.0 hours to obtain a uniform mixed aqueous phase system of surfactant and metal salt;

[0009] A3: Dissolve the reducing agent in 10 mL of deionized water;

[0010] A4: After the A2 mixed solution is naturally cooled to 35°C to 50°C, the dissolved reducing agent A3 solution is added to A2 at a rate of 6 drops / minute to 20 drops / minute. After the addition is complete, the temperature is increased to 70°C to 80°C at a rate of 5°C / minute to 10°C / minute. Keep warm for 0.5 to 1.5 hours, then add ethanol dropwise and continue stirring for 10 to 15 minutes.

[0011] A5: The mixed solution of A4 is subjected to centrifugation, anhydrous ethanol precipitation, and centrifugation washing operations in sequence, and the above washing operations are repeated three times to obtain amorphous iron, amorphous cobalt or amorphous nickel magnetic metal nanomaterials with a particle size of 10nm to 40nmrr.

[0012] Preferably, the surfactant in A1 is one or more of a polyaddition polymer of polypropylene glycol and ethylene oxide, polyethylene glycol, and polyvinyl pyrrolidone.

[0013] Preferably, if one surfactant in A1 is added, the molar mass is 0.03-0.12 mol; if any two are added, the molar mass of both are 0.02-0.06 mol; if three are added, the molar mass of all three are 0.01-0.02 mol.

[0014] Preferably, the metal citrate in A2 is any one of ferric citrate, cobalt citrate and nickel citrate.

[0015] Preferably, the amount of the metal citrate added in A2 is 0.02 to 0.5 mol.

[0016] Preferably, the reducing agent in A3 is any one of sodium borohydride, sodium cyanoborohydride, sodium citrate, and ascorbic acid, and the amount used is 1.5 to 4.5 times the amount of the metal citrate in A2.

[0017] Compared with the prior art, the present invention has the following advantages:

[0018] 1. The present invention first utilizes a simple one-step aqueous solution reduction method to produce three magnetic amorphous metal nanomaterials in gram-level yields, with uniform morphology and size. This "bottom-up" preparation method is fundamentally different from previous methods for preparing similar materials. The reaction is first carried out at a relatively low reaction temperature and a relatively low reducing agent concentration. A supersaturated state of the nucleation growth material is generated at a low temperature and at a uniform rate. When the supersaturated concentration exceeds the nucleation solubility, rapid nucleation occurs. The concentration of this growth material is raised to a very high saturation state, and then rapidly drops below the nucleation concentration, ensuring that all nuclei are generated at the same time and of the same size, resulting in smaller nuclei with a more uniform particle size distribution. The presence of a surfactant in the subsequent nucleus growth process affects the diffusion rate of the growth material from the liquid phase to the nucleus surface, and the concentration of the growth material is relatively low within a certain range. These factors make it easier for the prepared particles to form a single morphology and uniform size, as demonstrated in the specific examples.

[0019] 2. The surfactant added during the reaction first forms micelles in the reaction system and is naturally adsorbed on the particle surface through electrostatic adsorption or intermolecular interactions, ensuring that the citrate is always evenly dispersed in the reaction system during the nucleation stage and subsequent growth process of the reaction, weakening the magnetic pole-to-pole interaction. The good dispersion of the solution in the reaction system ensures the smooth progress of subsequent reaction steps; at the same time, it also causes the magnetic amorphous metal nanomaterial obtained by the reaction to be coated with a layer of hydrophilic substance, improving the dispersion stability of the material in the aqueous phase and making it more conducive to subsequent biomedical applications.

[0020] 3. The reducing agent is added to the reaction at a relatively low temperature (35°C to 50°C), and the low concentration of reducing agent is slowly added to the mixed solution reaction system, creating a supersaturated state of growth species concentration, a necessary condition for the formation of uniformly sized nanoparticles via the principle of uniform nucleation. Lowering the temperature of the saturated solution leads to a supersaturated state. As the temperature rises and the reducing agent is continuously added, the highly soluble metal citrate salt is converted into low-soluble metal nuclei. The rapid formation of a large number of nuclei under supersaturated conditions means that smaller nuclei with a more uniform particle size distribution can be formed. The formation of a large number of nuclei reduces the reactant concentration to below the nucleation concentration. The subsequent formation process involves the adsorption of the continuously formed zero-valent metal monomer onto the nucleus surface. This irreversible growth process promotes the formation of uniformly sized nanoparticles through diffusion-controlled growth. Simultaneously, a large amount of surfactant maintains the reactant concentration at a low level within a certain range, increasing the diffusion distance and also facilitating the formation of uniformly sized nanoparticles.

[0021] 4. The final washing process of the reaction will wash away the excess surfactant in the solution. A small amount of surfactant bound to the particle surface through electrostatic effects will still be coated on the particle surface, weakening the magnetic dipole interaction between the particles and forming a stable phenolic acid system. The anhydrous ethanol used for dispersion is dehydrated and deoxygenated in advance to ensure that the particles are dispersed in a water-free and oxygen-free environment, reducing the possibility of oxidation and extending the storage period.

[0022] 5. The present invention simply prepares three types of magnetic amorphous metal nanomaterials, and the particle size can be controlled by the reactant concentration, reaction temperature, and the dripping rate of the reducing agent. The prepared nanomaterials have a significant warming effect under magnetic field or near-infrared light irradiation, and can effectively remove oxidative components such as reactive oxygen free radicals (ROS). At the same time, because the material is in an energy metastable state, it is easier to reduce ROS, which can quickly and effectively clear oxidative mediators in the body. Therefore, it can be applied to multimodal thermal therapy mediated by magnetic field or near-infrared laser, including the treatment of inflammatory-related diseases such as rheumatoid arthritis, ulcerative colitis, and gout, and has very excellent biomedical application prospects.

[0023] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a TEM image of the magnetic amorphous iron nanomaterial according to Example 1 of the present invention.

[0025] Figure 2 This is a TEM image of the magnetic amorphous cobalt nanomaterial according to Example 2 of the present invention.

[0026] Figure 3This is a TEM image of the magnetic amorphous nickel nanomaterial according to Example 3 of the present invention.

[0027] Figure 4 This is a temperature rise curve of the magnetic amorphous iron nanomaterial according to Example 1 of the present invention under near-infrared light irradiation.

[0028] Figure 5 This is a temperature rise curve of the magnetic amorphous cobalt nanomaterial according to Example 2 of the present invention under near-infrared light irradiation.

[0029] Figure 6 This is the test result of the magnetic amorphous iron nanomaterial of Example 1 of the present invention for removing ROS in vitro. DETAILED DESCRIPTION

[0030] Example 1

[0031] The preparation method of the magnetic amorphous metal nanomaterial of this embodiment is as follows:

[0032] A1: Add 2.0 g of polypropylene glycol and ethylene oxide addition polymer, 2.5 g of polyethylene glycol, and 5.0 g of polyvinyl pyrrolidone to 100 mL of deionized water, stir, and introduce nitrogen as a protective gas. Raise the temperature to 60°C and maintain for 0.5 hours to drain all water and oxygen from the system.

[0033] A2: Add 12.25g of ferric citrate to A1, stir and disperse, and keep warm for 0.5 hours;

[0034] A3: Dissolve 3.78 g of sodium borohydride in 10 mL of deionized water;

[0035] A4: After the A2 mixed solution is naturally cooled to 40°C, the dissolved reducing agent A3 solution is added dropwise to A2 at a rate of 10 drops / minute. After the addition is complete, the temperature is raised to 80°C at a rate of 5°C / minute. The reaction is kept at this temperature for 0.5 hours. 20 mL of ethanol is then added dropwise and stirring is continued for 10 minutes.

[0036] A5: The mixed solution of A4 is subjected to centrifugation, anhydrous ethanol precipitation, and centrifugation washing operations, and the washing operations are repeated three times to obtain an amorphous iron nanomaterial coated with polyethylene glycol and polyvinyl pyrrolidone; the nanomaterial is dispersed in anhydrous and oxygen-free ethanol and stored in a sealed container.

[0037] From the TEM image ( Figure 1 ) It can be seen that the magnetic amorphous iron nanomaterial prepared in this embodiment has a regular spherical structure, an average particle size of 10nm to 15nm, and a uniform particle size distribution; the polymer layer structure is evenly coated on the particle surface; Figure 4 The results show that the nanomaterial prepared in this example has a high temperature rise performance under near-infrared light irradiation, and the temperature rise performance is better than that of the nanomaterial prepared in this example under near-infrared light irradiation.2 ) under ambient conditions, the temperature can be rapidly increased from room temperature (31°C) to 42°C within 5 minutes, making it suitable for physical hyperthermia treatment in the biomedical field. Furthermore, in vitro testing of the material's ROS scavenging capacity demonstrated its ability to rapidly and effectively remove oxidative species, potentially enabling its use in the treatment of inflammatory diseases.

[0038] Example 2

[0039] The preparation method of the magnetic amorphous metal nanomaterial of this embodiment is as follows:

[0040] A1: Add 3.0 g of polypropylene glycol and ethylene oxide addition polymer and 2.0 g of polyvinyl pyrrolidone to deionized water, stir and mix, introduce nitrogen as a protective gas, raise the temperature to 55°C, and maintain the temperature for 1.0 hour to drain all water and oxygen from the system;

[0041] A2: Add 14.06g of cobalt citrate to A1, stir and disperse, and continue to keep warm for 0.5 hours;

[0042] A3: Dissolve 3.78 g of sodium borohydride in 10 mL of deionized water;

[0043] A4: After the A2 mixed solution is naturally cooled to 35°C, the dissolved reducing agent A3 solution is added dropwise to A2 at a rate of 6 drops / minute. After the addition is complete, the temperature is raised to 75°C at a rate of 7°C / minute. The reaction is kept at this temperature for 1.0 hour. 20 mL of ethanol is then added dropwise and stirring is continued for 10 minutes.

[0044] A5: The mixed solution of A4 is subjected to centrifugation, anhydrous ethanol precipitation, and centrifugation washing operations, and the washing operations are repeated three times to obtain an amorphous cobalt nanomaterial coated with polyvinyl pyrrolidone; the nanomaterial is dispersed in anhydrous and oxygen-free ethanol and stored in a sealed container.

[0045] From the TEM image ( Figure 2 ) It can be seen that the magnetic amorphous cobalt nanomaterial prepared in this embodiment has a regular spherical structure, an average particle size of 10 to 15 nm, and a uniform particle size distribution; the polymer layer structure is evenly coated on the particle surface; Figure 5 The results show that the nanomaterial prepared in this example has a high temperature rise performance under near-infrared light irradiation, and the temperature rise performance is better than that of the nanomaterial prepared in this example under near-infrared light irradiation. 2 ) under normal conditions, the temperature can be rapidly raised from room temperature of 31°C to 42°C within 5 minutes, which can meet the needs of physical thermal treatment in the biomedical field.

[0046] Example 3

[0047] The preparation method of the magnetic amorphous metal nanomaterial of this embodiment is as follows:

[0048] A1: Add 3.0 g of polypropylene glycol and ethylene oxide addition polymer and 4.0 g of polyethylene glycol to deionized water, stir and mix, introduce nitrogen as a protective gas, raise the temperature to 65°C, and maintain the temperature for 1.5 hours to drain all water and oxygen from the system;

[0049] A2: Add 14.31 g of nickel citrate monohydrate to A1, stir to disperse, and continue to heat for 1.5 hours;

[0050] A3: Dissolve 1.89g of sodium borohydride in deionized water;

[0051] A4: After the A2 mixed solution is naturally cooled to 40°C, the dissolved reducing agent A3 solution is added dropwise to A2 at a rate of 6 drops / minute. After the addition is complete, the temperature is increased to 75°C at a rate of 10°C / minute. The reaction is kept at this temperature for 1.5 hours. 20 mL of ethanol is then added dropwise and stirring is continued for 10 minutes.

[0052] A5: The mixed solution of A4 is subjected to a washing process of centrifugation, anhydrous ethanol precipitation, and centrifugation. The washing process is repeated three times to obtain an amorphous cobalt nanomaterial coated with polyethylene glycol. The nanomaterial is dispersed in anhydrous and oxygen-free ethanol and stored in a sealed container.

[0053] From the TEM image ( Figure 3 ) It can be seen that the magnetic amorphous nickel nanomaterial prepared in this example has a regular spherical structure, an average particle size of 10-15 nm, and a uniform particle size distribution; the polymer layer structure is evenly coated on the particle surface. TMB (3,3',5,5'-tetramethylbenzidine) was used as a peroxidase substrate to characterize the ROS scavenging ability of the prepared material. The results are as follows Figure 6 As shown, it is confirmed that the prepared magnetic amorphous cobalt nanomaterials have a certain ability to scavenge ROS generated by the system and can be used to treat inflammatory-related diseases.

[0054] The present invention solves the problems in the nucleation and growth process of magnetic amorphous nanoparticles by regulating reaction parameters such as the heating rate, reaction temperature and reaction droplet acceleration during the one-step reduction method. The synthesis method is highly repeatable, and the obtained amorphous metal particles have uniform morphology and size and good dispersibility, which has important guiding significance for the preparation of amorphous metal nanoparticles.

Claims

1. A method for preparing a magnetic amorphous metal nanomaterial, characterized in that: The method comprises the following steps: A1. Add the surfactant to 100 mL of deionized water, stir to mix, introduce protective gas, raise the temperature to 50°C to 70°C, and keep the temperature for 0.5 to 2.0 hours to drain the water and oxygen in the system. A2. Add metal citrate to A1, stir and disperse, and continue to keep warm for 0.5-1.0 hours; A3: Dissolve the reducing agent in 10 mL of deionized water; A4: After the A2 mixed solution is naturally cooled to 35°C to 50°C, the dissolved reducing agent A3 solution is added to A2 at a rate of 6 drops / minute to 20 drops / minute. After the addition is complete, the temperature is raised to 70°C to 80°C at a rate of 5°C / minute to 10°C / minute. Keep warm for 0.5 to 1.5 hours. Add ethanol dropwise and continue stirring for 10 to 15 minutes. A5: The mixed solution of A4 is subjected to centrifugation, anhydrous ethanol precipitation, and centrifugation washing operations, and the washing operations are repeated three times to obtain amorphous iron, amorphous cobalt, or amorphous nickel magnetic metal nanomaterials with a particle size of 10 nm to 40 nm. The surfactant in A1 is a polyaddition polymer of polypropylene glycol and ethylene oxide, polyethylene glycol, or polyvinyl pyrrolidone; The metal citrate in A2 is any one of ferric citrate, cobalt citrate and nickel citrate.

2. The method for preparing a magnetic amorphous metal nanomaterial according to claim 1, wherein: The amount of the metal citrate added in A2 is 0.02 to 0.5 mol.

3. The method for preparing a magnetic amorphous metal nanomaterial according to claim 1, wherein: The reducing agent in A3 is any one of sodium borohydride, sodium cyanoborohydride, sodium citrate, and ascorbic acid, and its amount is 1.5 to 4.5 times the amount of the metal citrate in A2.

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