Magnetically responsive acidifying or alkalizing agent and preparation method and application thereof
The magnetically responded acid-base regulator uses Fe@Fe3O4 nanoparticles to heat up and decompose PLGA carriers under alternating magnetic field, solving the problems of large dosage, complex operation and secondary pollution of traditional acid-base regulation methods, and achieving fine acid-base regulation at low doses. It is suitable for cell culture and drug delivery systems in the field of biomedical science.
Patent Information
- Application Number
- CN202510338748.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-21
- Publication Date
- 2025-07-04
AI Technical Summary
Traditional acid-base regulation methods are large in dosage, complex in operation, easy to produce secondary pollution and difficult to achieve accurate local regulation. The application of magnetic nanomaterials in biomedicine has problems of dispersion and magnetic properties, making it difficult to achieve effective acid-base regulation.
Using magnetically responded acid-base regulators, Fe@Fe3O4 nanoparticles are used to heat up under the alternating magnetic field and decompose the PLGA carrier to release the internal alkali solution to regulate acid-base. Through the efficient magneto-thermal effect of Fe@Fe3O4 and the appropriate temperature decomposition performance of PLGA, the accurate release of alkaline solution is achieved.
It realizes fine acid and alkali regulation at low doses, is easy to operate, is environmentally friendly, can be controlled through external magnetic field, and is suitable for cell culture, drug delivery systems, etc. in the field of biomedical science.
Smart Images
Figure CN120242006A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical fields of nanomaterials and biomedicine, and particularly to a magnetic-responsive acid-base regulator, a preparation method thereof, and an application thereof. Background Art
[0002] In the field of biomedicine, the regulation of acid-base balance is crucial for the normal physiological functions of cells. During the cell metabolism process, a large amount of acidic or alkaline substances are generated. If not regulated in time, it will lead to the imbalance of the intracellular environment, thereby affecting processes such as cell growth, differentiation, and apoptosis. In addition, in drug delivery systems, the regulation of the acid-base environment also has a significant impact on drug release and bioavailability. However, traditional acid-base regulation methods have many limitations, such as large amounts of chemical reagents used, complex operations, easy generation of secondary pollution, etc., and it is difficult to achieve precise local regulation.
[0003] In recent years, magnetic nanomaterials have received extensive attention in the field of biomedicine due to their unique magnetic properties, good biocompatibility, and controllable drug release characteristics. Especially superparamagnetic Fe3O4 nanoparticles can respond rapidly under the action of an external magnetic field and have good dispersibility and stability. However, the current applications of magnetic materials in biomedicine acid-base regulation are relatively few, and there are problems such as poor dispersibility of large particles and poor magnetism of small particles, making it difficult to achieve a good acid-base regulation function. Summary of the Invention
[0004] The first object of the present invention is to provide a magnetic-responsive acid-base regulator in view of the deficiencies of traditional acid-base regulation methods. This regulator utilizes the property of magnetic nanoparticles to heat up under an alternating magnetic field, and realizes the release of an alkaline solution through the decomposition of the carrier, thereby regulating the acidity and alkalinity of the environment. Specifically, this regulator includes a carrier, magnetic nanoparticles embedded in the carrier, and an internal alkaline solution. The carrier is a hollow poly(lactic-co-glycolic acid) (PLGA) microsphere, which has good biocompatibility and degradability. The embedded magnetic nanoparticles are Fe@Fe3O4 with a core-shell structure, and this core-shell structure can improve the magnetic responsiveness and stability of the material. The internal alkaline solution can be sodium bicarbonate, NaOH, polyethyleneimine, etc., and these solutions can effectively regulate the acidity and alkalinity of the environment after release.
[0005] The magnetic-responsive acid-base regulator of the present invention has the advantages of less dosage, simple operation, environmental friendliness, etc., and can be used through an external magnetic field. This regulator has broad application prospects in aspects such as cell culture and drug delivery systems in the field of biomedicine.
[0006] To achieve the above object, the present invention adopts the following technical solutions: A magnetic-responsive acid-base regulator, wherein the magnetic-responsive acid-base regulation should at least include a transition from acidic, neutral or weakly basic to basic under an alternating magnetic field; characterized in that the magnetic-responsive acid-base regulator includes a carrier, magnetic nanoparticles embedded in the carrier, and an internal alkaline solution; due to the presence of the magnetic nanoparticles, the magnetic-responsive acid-base regulator will heat up again under the action of the alternating magnetic field and cause the carrier to decompose, so as to release the alkaline solution to adjust the acidity and alkalinity of the environment.
[0007] Preferably, the carrier is a hollow poly(lactic-co-glycolic acid) (PLGA) microsphere, the nanoparticles embedded in the carrier are Fe@Fe3O4 with a core-shell structure, and the internal alkaline solution is sodium bicarbonate, NaOH or polyethyleneimine.
[0008] Preferably, the diameter of the hollow PLGA microsphere is 100 nm - 500 nm, and the diameter of the Fe@Fe3O4 nanoparticles is 3 - 20 nm.
[0009] The usage method of the above magnetic-responsive acid-base regulator is: applying an alternating magnetic field to the acid-base regulator.
[0010] Preferably, for a 10 mg / mL acid-base regulator under an alternating magnetic field with a magnetic field strength of 2 kA / m, the concentration change of hydroxide ions can reach 10 -4 M within 1 minute.
[0011] The second object of the present invention is to provide a preparation method of a magnetic-responsive acid-base regulator, including the following steps: Step (1), preparing Fe@Fe3O4 nanoparticles by a thermal decomposition method; Step (2), using an alkaline Tris aqueous solution and a dichloromethane solution containing PLGA and Fe@Fe3O4 nanoparticles to form a two-phase solution, and forming a water-in-oil emulsion under ultrasonic treatment; Step (3), adding water again, and forming a water-in-oil-in-water emulsion under ultrasonic treatment.
[0012] Step (4), standing at room temperature for 24 h to volatilize the dichloromethane in the oil phase, and obtaining the acid-base regulator.
[0013] Preferably, in step (1), the Fe@Fe3O4 nanoparticles are obtained by thermal decomposition of an organic precursor of iron in an inert atmosphere and an oil-phase solution, and are washed with a hexane solution and used after centrifugation. First step: Mix an organic precursor of iron (such as Fe(CO)5, Fe(acac)3), a solvent (ODE), and a reducing agent (OA or OAm), heat to 100-120 °C, and stir until completely dissolved. Second step: Under the protection of an inert gas (such as nitrogen or argon), heat the solution to 120-180 °C and keep it for 30 minutes to 2 hours to decompose the organic precursor of iron to generate Fe nanoparticles; after the reaction ends, naturally cool to room temperature and form an outer layer of Fe3O4 by surface oxidation under natural conditions. Third step: Disperse with a hexane solution and precipitate with an ethanol solution for washing to obtain Fe@Fe3O4 nanoparticles.
[0014] Preferably, the alkaline Tris aqueous solution in step (2) is an aqueous solution of sodium bicarbonate, NaOH, or a mixture of polyethyleneimine and tris(hydroxymethyl)aminomethane; the Fe@Fe3O4 nanoparticles and PLGA are uniformly dispersed in a dichloromethane solution together. Preferably, the volume ratio of the alkaline Tris aqueous solution to the dichloromethane solution in step (2) is 1:(5-10). The ultrasonic power is 40-200 W, and the frequency is 10 kHz-80 kHz.
[0015] Preferably, the volume of the aqueous solution added in step (3) is 3-10 times the volume of the water-in-oil emulsion in step (2). The ultrasonic power is 40-200 W, and the frequency is 10 kHz-80 kHz.
[0016] The acid-base regulator material of the present invention is mainly formed by two immiscible solvents (usually an oil phase and an aqueous phase) to form a stable microemulsion under the action of a surfactant. The preparation of this material is through a two-step emulsion method. In the first step, since the Fe@Fe3O4 nanoparticles and PLGA have good dispersibility in a dichloromethane solution, in the case of a large amount of dichloromethane solution and a small amount of water, an aqueous emulsion dispersed in the dichloromethane solution can be obtained by ultrasonic treatment. In the second step, in the case of a large amount of water and a small amount of the above emulsion, a dichloromethane emulsion dispersed in water can be obtained by ultrasonic treatment. After the formed dichloromethane emulsion volatilizes, only the Fe@Fe3O4 nanoparticles and PLGA remain to form hollow spheres that encapsulate water and are dispersed in water.
[0017] The third object of the present invention is to provide an application of a magnetic-responsive acid-base regulator in the pH adjustment of a solution. The pH adjustment of the solution includes the following application scenarios: industrial wastewater treatment, pH adjustment of a culture medium, pH adjustment of a wound, and pH adjustment of a tumor microenvironment, and is characterized in that it at least includes using an alternating magnetic field to increase the alkalinity of the solution; The magnetic-responsive acid-base regulator includes a carrier, magnetic nanoparticles embedded in the carrier, and an alkaline solution inside the carrier; due to the presence of the magnetic nanoparticles, the magnetic-responsive acid-base regulator will heat up again under the action of an alternating magnetic field and cause the carrier to decompose, so as to release the alkaline solution to adjust the acidity and alkalinity of the environment.
[0018] Therefore, the present invention has the following beneficial effects: The present invention solves the disadvantages of traditional acid-base regulation methods through the efficient magnetic heating effect of Fe@Fe3O4, the temperature-appropriate decomposition performance of PLGA, and their embedded combination. First, traditional acid-base regulation methods have large dosages of agents, complex operations, are prone to secondary pollution, and have low precision, and cannot achieve fine acid-base control. The present invention can achieve fine acid-base regulation at low dosages and can be controlled remotely. Second, compared with other magnetic materials, Fe@Fe3O4 nanoparticles have a more efficient magnetic heating effect and the embedded form of the nanoparticles has a better effect of degrading PLGA, and thus can achieve efficient internal solution release and acid-base regulation.
[0019] The magnetic-responsive acid-base regulator of the present invention has the advantages of small dosage, simple operation, environmental friendliness, etc., and can be controlled by an external magnetic field, and has broad application prospects in industrial wastewater treatment, medium pH adjustment, wound pH adjustment, tumor microenvironment adjustment, etc. Description of the Drawings
[0020] Figure 1 It is a schematic structural diagram of the active ingredient of the acid-base regulator in Example 1.
[0021] Figure 2 It is a preparation mechanism diagram of the acid-base regulator in Example 1.
[0022] Figure 3 It is a TEM diagram of Fe@Fe3O4 nanoparticles in Example 1.
[0023] Figure 4 It is an SEM diagram of the active ingredient of the acid-base regulator in Example 1.
[0024] Figure 5 It is a TEM diagram of the active ingredient of the acid-base regulator in Example 1.
[0025] Figure 6 It is a temperature change curve diagram of the acid-base regulator in Test Example 1 in an alternating magnetic field.
[0026] Figure 7 It is a pH value change curve diagram of the acid-base regulator in Test Example 2 in an alternating magnetic field.
[0027] Figure 8 It is an SEM diagram of the acid-base regulator encapsulated with polyethyleneimine in Example 2.
[0028] Figure 9 TEM image of the acid-base regulator encapsulated with polyethyleneimine in Example 2.
[0029] Figure 10 Curve graph of the pH value change of the acid-base regulator in an alternating magnetic field in Test Example 3. Detailed implementation manners
[0030] The present invention will be further described below in conjunction with the accompanying drawings of the specification and specific embodiments. Those of ordinary skill in the art will be able to implement the present invention based on these descriptions. In addition, the embodiments of the present invention involved in the following description are usually only a part of the embodiments of the present invention, rather than all of the embodiments. Therefore, based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention. The following uses specific embodiments to illustrate the technical solutions of the present invention, but the protection scope of the present invention is not limited thereto. Example 1
[0031] Firstly, Fe@Fe3O4 nanoparticles were prepared by the thermal decomposition method. In a four-necked flask, 1-octadecene (20 mL) and oleylamine (0.3 mL, 1 mmol) were magnetically stirred and degassed under an argon atmosphere. The solution was heated to 120 °C and maintained for 30 minutes, and then heated to 180 °C. Then, under an argon atmosphere, Fe(CO)5 (0.7 mL, 5 mmol) was added, and the reaction mixture was maintained at 180 °C for 30 minutes. After about 20 minutes, it was observed that the color changed from orange to brown and black. The solution was cooled to 160 °C, and oleic acid (0.3 mL, 1 mmol) was added. The resulting solution was aged at 160 °C for 30 minutes. After cooling, the supernatant was removed, and the nanoparticles were washed with n-hexane and ethanol to synthesize Fe@Fe3O4 nanoparticles.
[0032] 50 mg of the obtained Fe@Fe3O4 nanoparticles and 25 mg of PLGA were dispersed in 1 mL of dichloromethane solution. 0.1 mL of 0.2 M Tris solution was prepared and 0.2 M sodium bicarbonate was added. Subsequently, the two were mixed, and ultrasonic cleaning was performed using an ultrasonic cleaner under the conditions of 40 kHz and 100 W for 3 minutes to obtain a water-in-oil emulsion. 5 mL of deionized water was added to the water-in-oil emulsion, and ultrasonic cleaning was performed again using an ultrasonic cleaner under the conditions of 40 kHz and 100 W to obtain a water-in-oil-in-water emulsion. Finally, the solution was placed in a ventilated place for 24 h to obtain the acid-base regulator.
[0033] Figure 1It is a structural schematic diagram of the active ingredient of the obtained acid-base regulator. Overall, it is hollow PLGA microspheres dispersed in water. Fe@Fe3O4 nanoparticles are embedded in the microspheres, and a sodium bicarbonate solution is contained inside. Figure 2 It is a preparation mechanism diagram of the acid-base regulator.
[0034] Figure 3 It is a TEM image of Fe@Fe3O4 nanoparticles. The nanoparticles have a core-shell structure, with the core being elemental iron and the shell being magnetite.
[0035] Figure 4 It is a SEM image of the finally prepared acid-base regulator. The morphology is microspheres at the nanoscale.
[0036] Figure 5 It is a TEM image of the finally prepared acid-base regulator. Fe@Fe3O4 nanoparticles can be observed embedded in the microspheres, and there are hollow parts. It can be seen from the figure that the nanoparticles and PLGA are fused together, and there are no nanoparticles in some areas, indicating that this area is hollow. This characteristic of high signal around and no signal in the middle is a feature of the hollow structure.
[0037] Test Example 1 Take the acid-base regulators with different concentrations in Example 1, place them under an alternating magnetic field of 2 kA / m for a certain period of time, and use an optical fiber to monitor the temperature change during this period. As Figure 6 shown, the solution temperature continuously increases with time, and the higher the concentration of the acid-base regulator, the more obvious the temperature change. It can increase by 20°C within a few minutes, and the decomposition of PLGA can be achieved.
[0038] Test Example 2 Take 1 mL of the acid-base regulator with a concentration of 30 mg / mL, add it to 2 mL of deionized water, and while heating with an alternating magnetic field of 2 kA / m, use a pH meter to measure its pH value at different times. As Figure 7 shown, the solution pH continuously increases with time and finally reaches a pH value of 10. Example 2
[0039] Disperse 50 mg of Fe@Fe3O4 nanoparticles and 25 mg of PLGA in Example 1 in 1 mL of dichloromethane solution. Prepare 0.2 mL of 0.2 M Tris solution and add 0.01 M polyethyleneimine. Subsequently, mix the two, and use an ultrasonic cell disruptor to ultrasonicate at a frequency of 20 kHz with a power of 40 W for 1 s and stop for 0.5 s for 2 minutes to obtain a water-in-oil emulsion. Add 10 mL of deionized water to the water-in-oil emulsion and ultrasonicate at a frequency of 20 kHz with a power of 40 W for 1 s and stop for 0.5 s for 2 minutes to obtain a water-in-oil-in-water emulsion. Finally, place the solution in a ventilated place for 24 h to obtain an acid-base regulator encapsulated with polyethyleneimine.
[0040] Figure 8 SEM image of the obtained acid-base regulator encapsulated with polyethyleneimine, showing a nanoscale microsphere morphology.
[0041] Figure 9 TEM image of the obtained acid-base regulator encapsulated with polyethyleneimine. Fe@Fe3O4 nanoparticles can be observed embedded in the microspheres, and there are hollow parts. Due to the use of a larger proportion of the aqueous phase component, the hollow parts are relatively large.
[0042] Test Example 3 Take 1 mL of the acid-base regulator at a concentration of 30 mg / mL, add it to 2 mL of deionized water, and while heating with an alternating magnetic field of 2 kA / m, use a pH meter to measure its pH value at different times. As Figure 10 shown, due to more basic components, it has a slightly higher acid-base regulation ability. The pH of the solution continuously increases over time and can ultimately reach a pH value of 10.5, and the concentration change of hydroxide ions can reach 10 -4 M.
[0043] As described above, the above is only the specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.
Claims
1. A magnetic-responsive acid-base regulator, wherein the magnetic-responsive acid-base regulation should at least include a transition from acidic, neutral or weakly basic to basic under an alternating magnetic field; characterized in that, The magnetic-responsive acid-base regulator includes a carrier, magnetic nanoparticles embedded in the carrier, and an alkaline solution inside the carrier; due to the presence of the magnetic nanoparticles, the magnetic-responsive acid-base regulator will heat up again under the action of an alternating magnetic field and cause the carrier to decompose, so that the alkaline solution releases to adjust the acidity and alkalinity of the environment.
2. The acid-base regulator with magnetic response according to claim 1, characterized in that: The carrier is a hollow poly(lactic-co-glycolic acid) (PLGA) microsphere, the nanoparticles embedded in the carrier are Fe@Fe3O4 with a core-shell structure, and the alkaline solution inside the carrier is one of sodium bicarbonate, NaOH, or polyethyleneimine.
3. The acid-base regulator with magnetic response according to claim 1, characterized in that: The diameter of the hollow PLGA microsphere is 100 nm - 500 nm, and the diameter of the Fe@Fe3O4 nanoparticles is 3 - 20 nm.
4. A magnetic response acid-base regulator according to claim 1, characterized in that: The concentration change of hydroxide ions of the acid-base regulator at 100 mg / mL can reach 10 -4 M within 1 minute under an alternating magnetic field with a magnetic field strength of 2 kA / m.
5. The preparation method of a magnetic response acid-base regulator according to any one of claims 1-4, characterized in that, It includes the following steps: Step (1): Prepare Fe@Fe3O4 nanoparticles by the thermal decomposition method; Step (2): Use an alkaline Tris aqueous solution and a dichloromethane solution containing PLGA and Fe@Fe3O4 nanoparticles to form a two-phase solution, and form a water-in-oil emulsion under ultrasonic waves; Step (3): Add water again and form a water-in-oil-in-water emulsion under ultrasonic waves; Step (4): Place it at room temperature for 24 h to volatilize the dichloromethane in the oil phase and obtain the acid-base regulator.
6. The preparation method of the magnetic response acid-base regulator according to claim 5, characterized in that: In step (1), the Fe@Fe3O4 nanoparticles are obtained by the high-temperature decomposition of an iron organic precursor in an inert atmosphere and an oil-phase solution, and are washed and centrifuged with a hexane solution for use. The specific steps are as follows: The first step: Mix the iron organic precursor with a solvent and a reducing agent, heat to 100 - 120 °C, and stir until completely dissolved; The second step: Under the protection of an inert gas, heat the solution to 120 - 180 °C and keep it for 30 minutes to 2 hours to decompose the iron organic precursor to generate Fe nanoparticles; after the reaction ends, naturally cool to room temperature and form an outer layer of Fe3O4 by surface oxidation under natural conditions; The third step: Dispersed with a hexane solution and precipitated with an ethanol solution for washing to obtain Fe@Fe3O4 nanoparticles; The solvent is ODE, and the reducing agent is OA or OAm.
7. The preparation method of the magnetoresponsive acid-base regulator according to claim 5, characterized in that: The alkaline Tris aqueous solution in step (2) is a mixed aqueous solution of sodium bicarbonate, NaOH, or polyethyleneimine and tris(hydroxymethyl)aminomethane; the Fe@Fe3O4 nanoparticles and PLGA are uniformly dispersed in the dichloromethane solution together.
8. The preparation method of the magnetic response acid-base regulator according to claim 5, characterized in that: In step (2), the volume ratio of the alkaline Tris aqueous solution to the dichloromethane solution is 1:(5 - 10), the ultrasonic power is 40 - 200 W, and the frequency is 10 - 80 kHz.
9. The preparation method of the magnetic response acid-base regulator according to claim 5, characterized in that: In step (3), the volume of the aqueous solution added is 5 - 10 times the volume of the water-in-oil emulsion in step (2), the ultrasonic power is 40 - 200 W, and the frequency is 20 - 80 kHz.
10. Use of a magnetoresponsive acid-base regulator according to any one of claims 1-4 in the regulation of the pH of a solution, wherein the regulation of the pH of the solution includes the following application scenarios: industrial wastewater treatment, pH regulation of a culture medium, pH regulation of a wound, regulation of a tumor microenvironment; characterized in that, It includes at least using an alternating magnetic field to increase the alkalinity of the solution; The magnetic-responsive acid-base regulator includes a carrier, magnetic nanoparticles embedded in the carrier, and an alkaline solution inside the carrier; due to the presence of the magnetic nanoparticles, the magnetic-responsive acid-base regulator will heat up again under the action of an alternating magnetic field and cause the carrier to decompose, so that the alkaline solution releases to adjust the acidity and alkalinity of the environment.