Multicore magnetic ferrite nanoparticles, method for preparing the same and use thereof
Patent Information
- Application Number
- CN202611253018.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-08-18
- Publication Date
- 2026-09-29
AI Technical Summary
[0003]本发明的第一个目的是提供一种多核磁性铁氧体纳米颗粒以解决现有的单核磁性纳米颗粒由于其尺寸小、磁学性能弱导致其在生物体诊-疗中应用受限的技术问题
本发明首次提出了瞬时高温分解成核的方法，将金属前驱体逐滴滴加至高温的溶液B中，利用金属前驱体瞬时高温分解形成多核聚集体，成功制备了尺寸为20-70 nm的多核磁性铁氧体纳米颗粒，增强了EPR效应，促进多核磁性铁氧体纳米颗粒在肿瘤位置的选择性分布。同时，由于多核磁性铁氧体纳米颗粒单晶之间的耦合作用，多核磁性铁氧体纳米颗粒具有更强的饱和磁化强度，增强了多核磁性铁氧体纳米颗粒的磁共振成像图像质量和分辨率。
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Figure CN122828155A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of magnetic nanoparticle technology, specifically relating to a multinuclear magnetic ferrite nanoparticle, its preparation method, and its application. Background Technology
[0002] Magnetic ferrite nanoparticles are widely used in targeted drug delivery, magnetic resonance imaging (MRI), and other fields due to their excellent magnetic responsiveness, biocompatibility, biodegradability, and surface modifiability. However, mononuclear magnetic ferrite nanoparticles are small in size, generally less than 10 nm, resulting in poor selective distribution in tumor tissues through high permeability and retention effect (EPR effect), and low targeted delivery efficiency in vivo. Furthermore, mononuclear nanoparticles have weak magnetic properties, leading to low resolution in MRI. These limitations restrict the application of mononuclear magnetic ferrite nanoparticles in biological diagnosis and treatment. Increasing the size of mononuclear nanoparticles can meet the size requirements for a good EPR effect, but this often leads to aggregation of magnetic nanoparticles, reducing their stability in vivo. Therefore, constructing multinuclear magnetic nanoparticles is a good strategy to address the problems existing in the application of mononuclear magnetic nanoparticles. Summary of the Invention
[0003] The first objective of this invention is to provide a multinuclear magnetic ferrite nanoparticle to solve the technical problem that the application of existing mononuclear magnetic nanoparticles in biological diagnosis and treatment is limited due to their small size and weak magnetic properties.
[0004] The second objective of this invention is to provide a method for preparing multinuclear magnetic ferrite nanoparticles.
[0005] A third objective of this invention is to provide an application of multinuclear magnetic ferrite nanoparticles.
[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing multinuclear magnetic ferrite nanoparticles includes the following steps: dissolving a metal precursor in a polyol solvent to obtain a mixed solution A; heating the polyol solvent to obtain a solution B; adding the mixed solution A dropwise to the hot solution B, heating the reaction, adding a precipitant, and then washing and drying to obtain the final product.
[0007] Furthermore, the heating temperature for obtaining solution B by heating the polyol solvent is 200-280 °C, and the heating of solution B is carried out under an inert gas; the inert gas is nitrogen or argon.
[0008] Furthermore, the dropping rate of the mixed solution A into the hot solution B is 2-10 mL / h.
[0009] Furthermore, the heating temperature of the heating reaction is 200-280 °C, and the reaction time is 0.5-2 h.
[0010] Furthermore, the volume ratio of the mixed solution A to the solution B is 1:2 to 1:10; the molar amount of the metal precursor in the mixed solution A to the volume ratio of the polyol solvent is 0.1-1 mol:1 mL.
[0011] Furthermore, the metal precursor is iron acetylacetone; the polyol solvent is triethylene glycol; the precipitant is ethyl acetate, and the total volume ratio of the polyol solvent to the precipitant is 1:1 to 1:5.
[0012] Furthermore, the metal precursor may also include one or more of cobalt acetylacetonate and nickel acetylacetonate.
[0013] A multinuclear magnetic ferrite nanoparticle was prepared using the above-described method for preparing multinuclear magnetic ferrite nanoparticles.
[0014] Application of a multinuclear magnetic ferrite nanoparticle as a drug carrier.
[0015] Application of a multinuclear magnetic ferrite nanoparticle as a contrast agent in magnetic resonance imaging.
[0016] The beneficial effects of this invention are: This invention proposes for the first time a method for instantaneous high-temperature decomposition and nucleation. A metal precursor is added dropwise to a high-temperature solution B, and the instantaneous high-temperature decomposition of the metal precursor forms multinuclear aggregates, successfully preparing multinuclear magnetic ferrite nanoparticles with sizes of 20-70 nm. This enhances the EPR effect and promotes the selective distribution of multinuclear magnetic ferrite nanoparticles at tumor sites. Simultaneously, due to the coupling effect between the single crystals of the multinuclear magnetic ferrite nanoparticles, the nanoparticles exhibit stronger saturation magnetization, enhancing the image quality and resolution of magnetic resonance imaging (MRI) of the multinuclear magnetic ferrite nanoparticles. Attached Figure Description
[0017] Figure 1 This is a TEM image of the multinuclear magnetic ferrite nanoparticles in Example 1; Figure 2 This is a TEM image of the multinuclear magnetic ferrite nanoparticles in Example 2; Figure 3 TEM image of mononuclear magnetic ferrite nanoparticles in Comparative Example 1; Figure 4 TEM image of mononuclear magnetic ferrite nanoparticles in Comparative Example 2; Figure 5 The XRD patterns of the magnetic ferrite nanoparticles in Examples 1, 2 and 1 are shown. Figure 6 The images show hysteresis loop diagrams of the magnetic ferrite nanoparticles in Examples 1, 2, and Comparative Example 1, where A is the hysteresis loop diagram and B is a magnified view of the low magnetic field region. Detailed Implementation
[0018] The present invention will be further described below with reference to the embodiments and accompanying drawings.
[0019] Example 1 The preparation method of the multinuclear magnetic ferrite nanoparticles in Example 1 includes the following steps: S1: Add 4 mmol of ferric acetylacetone to 10 mL of fully degassed triethylene glycol solution, and sonicate to fully dissolve and disperse the ferric acetylacetone to obtain mixed solution A; S2: Add 30 mL of fully degassed triethylene glycol solution to a round-bottom flask, heat to 280°C under argon protection, and obtain solution B; S3: Mixed solution A was added dropwise to solution B at 280 °C at a rate of 7 mL / h. Iron acetylacetone decomposed, nucleated, and grew instantaneously in solution B at 280 °C, forming a black solid. After all mixed solution A was added to solution B, the reaction temperature was maintained at 280 °C and the mixture was stirred continuously for 1 h. The reaction system was then cooled to 30 °C, 40 mL of ethyl acetate was added, and the mixture was washed with ethanol and dried in an oven to obtain black multinucleated magnetic ferrite nanoparticles.
[0020] Example 2 The preparation method of the multinuclear magnetic ferrite nanoparticles in Example 2 includes the following steps: S1: Add 8 mmol of ferric acetylacetone to 10 mL of fully degassed triethylene glycol solution, and sonicate to fully dissolve and disperse the ferric acetylacetone to obtain mixed solution A; S2: Add 30 mL of fully degassed triethylene glycol solution to a round-bottom flask, and heat to 280 °C under argon gas protection to obtain solution B; S3: Mixed solution A was added dropwise to solution B at 280 °C at a rate of 7 mL / h. Iron acetylacetone decomposed, nucleated, and grew instantaneously in solution B at 280 °C, forming a black solid. After all mixed solution A was added to solution B, the reaction temperature was maintained at 280 °C and the mixture was stirred continuously for 1 h. The reaction system was cooled to 30 °C, 40 mL of ethyl acetate was added, and the mixture was then repeatedly washed with ethanol and dried in an oven to obtain black multinucleated magnetic ferrite nanoparticles.
[0021] Example 3 The preparation method of the multinuclear magnetic ferrite nanoparticles in Example 3 includes the following steps: S1: Add 7 mmol of ferric acetylacetone and 1 mmol of cobalt acetylacetone to 10 mL of fully degassed triethylene glycol solution, and sonicate to fully dissolve and disperse the ferric acetylacetone and cobalt acetylacetone to obtain mixed solution A; S2: Add 30 mL of fully degassed triethylene glycol solution to a round-bottom flask, and heat to 280 °C under argon gas protection to obtain solution B; S3: Mixed solution A was added dropwise to solution B at 280 °C at a rate of 7 mL / h. Iron acetylacetone and cobalt acetylacetone decomposed, nucleated, and grew instantaneously in solution B at 280 °C, forming a black solid. After all mixed solution A was added to solution B, the reaction temperature was maintained at 280 °C and the mixture was stirred continuously for 1 h. The reaction system was cooled to 30 °C, 40 mL of ethyl acetate was added, and the mixture was then repeatedly washed with ethanol and dried in an oven to obtain black cobalt-doped multinuclear magnetic ferrite nanoparticles.
[0022] Comparative Example 1 The preparation method of the mononuclear magnetic ferrite nanoparticles of Comparative Example 1 includes the following steps: 4 mmol of ferric acetylacetone was added directly to 40 mL of fully degassed triethylene glycol solution, and the ferric acetylacetone precursor was sonicated to fully dissolve and disperse, resulting in a mixed solution. The mixed solution was added to a round-bottom flask and heated to 280 °C under argon gas protection while stirring. After the temperature of the mixed solution reached 280 °C, it was continued to be heated at this temperature and stirred continuously for 1 h. The reaction system was cooled to 30 °C, 40 mL of ethyl acetate was added, and then the mixture was repeatedly washed with ethanol and dried in an oven to obtain black mononuclear magnetic ferrite nanoparticles.
[0023] Comparative Example 2 The preparation method of the magnetic ferrite nanoparticles in Comparative Example 2 includes the following steps: S1: Add 4 mmol of acetylacetone iron to 10 mL of fully degassed triethylene glycol solution, and sonicate to fully dissolve and disperse the acetylacetone iron precursor to obtain mixed solution A; S2: Add 30 mL of fully degassed triethylene glycol solution to a round-bottom flask, and heat to 180 °C under argon gas protection to obtain solution B; S3: Add mixed solution A dropwise to solution B at 180 °C at a rate of 7 mL / h, while maintaining heating and continuous stirring; after all mixed solution A has been added to solution B at 180 °C, raise the temperature of the reaction system to 280 °C and continue stirring for 1 h; cool the reaction system to 30 °C, add 40 mL of ethyl acetate, then wash repeatedly with ethanol, and dry in an oven to obtain black mononuclear magnetic ferrite nanoparticles.
[0024] from Figure 1It can be seen that the multinuclear magnetic ferrite nanoparticles in Example 1 exhibit an aggregated morphology and uniform size. The average particle size of the multinuclear magnetic ferrite nanoparticles in Example 1 is 29.66 ± 3.87 nm. Figure 2 It can be seen that the multinuclear magnetic ferrite nanoparticles in Example 2 exhibit an aggregated morphology and uniform size. The average particle size of the multinuclear magnetic ferrite nanoparticles in Example 2 is 67.73 ± 8.08 nm, indicating that the size of the multinuclear magnetic ferrite nanoparticles can be controllably changed by altering the concentration of the metal precursor. Figure 3 It can be seen that the magnetic ferrite nanoparticles in Comparative Example 1 exhibit a mononuclear morphology, unlike the multinuclear aggregate morphology of Examples 1 and 2. This indicates that slowly heating the mixed solution to the reaction temperature cannot form a multinuclear aggregate morphology. The size of the mononuclear magnetic ferrite nanoparticles in Comparative Example 1 is 8.23 ± 1.30 nm. Figure 4 It can be seen that when the temperature of solution B is low, the mixed solution A cannot decompose instantaneously to generate unstable crystal nuclei when added to solution B. Therefore, stable polynuclear magnetic ferrite nanoparticles cannot be formed in this system. The particle size of the mononuclear magnetic ferrite nanoparticles in Comparative Example 2 is 10.27 ± 1.30 nm. According to Figure 5 As a result, the single-crystal size of the nanoparticles can be calculated based on the Scherrer formula. The single-crystal sizes of the multinuclear magnetic ferrite nanoparticles in Examples 1 and 2 are 16.16±2.17 nm and 19.21±2.29 nm, respectively, which are much smaller than 29.66±3.87 nm and 67.73±8.08 nm, indicating that the nanoparticles obtained in Examples 1 and 2 are multinuclear aggregates. In contrast, the single-crystal size of the mononuclear magnetic ferrite nanoparticles in Comparative Example 1 is 7.77±0.74 nm, which is only slightly different from 8.23±1.30 nm, proving that the nanoparticles prepared in Comparative Example 1 are mononuclear magnetic ferrite nanoparticles. Figure 6 As shown in Figure A, both Examples 1 and 2 exhibit high saturation magnetization, approximately 75-80 emu / g, and quickly reach magnetic saturation even at relatively low magnetic field strengths, indicating that the nanoparticles of Examples 1 and 2 possess good magnetic response capabilities. The saturation magnetization of Example 2 is slightly higher than that of Example 1, suggesting that its magnetic response capability increases with size, resulting in higher image quality and resolution in magnetic resonance imaging. In contrast, the saturation magnetization of the mononuclear magnetic ferrite nanoparticles obtained in Comparative Example 1 is significantly lower, approximately 50 emu / g. Figure 6As can be seen from B in the figure, compared with Comparative Example 1, the multinuclear magnetic ferrite nanoparticles of Example 1 and Example 2 still exhibit weaker remanence and coercivity. However, after the magnetic field is removed, their coercivity and remanence are close to zero, indicating that the nanoparticles of Example 1 and Example 2 have certain superparamagnetic properties, are not prone to agglomeration in solution, and can be stably dispersed.
Claims
1. A method for preparing multinuclear magnetic ferrite nanoparticles, characterized in that, Includes the following steps: The metal precursor is dissolved in a polyol solvent to obtain a mixed solution A; Solution B is obtained by heating the polyol solvent; Mixed solution A is added dropwise to hot solution B, heated to react, and then a precipitant is added. The mixture is then washed and dried to obtain the final product.
2. The method for preparing multinuclear magnetic ferrite nanoparticles according to claim 1, characterized in that, The heating temperature for obtaining solution B by heating the polyol solvent is 200-280 °C, and the heating of solution B is carried out under an inert gas; the inert gas is nitrogen or argon.
3. The method for preparing multinuclear magnetic ferrite nanoparticles according to claim 1, characterized in that, The mixed solution A is added dropwise to the hot solution B at a rate of 2-10 mL / h.
4. The method for preparing multinuclear magnetic ferrite nanoparticles according to claim 1, characterized in that, The heating temperature for the heating reaction is 200-280 ℃, and the reaction time is 0.5-2 h.
5. The method for preparing multinuclear magnetic ferrite nanoparticles according to claim 1, characterized in that, The volume ratio of the mixed solution A to the solution B is 1:2 to 1:10; the molar amount of the metal precursor in the mixed solution A is 0.1-1 mol:1 mL.
6. The method for preparing multinuclear magnetic ferrite nanoparticles according to claim 1, characterized in that, The metal precursor is iron acetylacetone; the polyol solvent is triethylene glycol; the precipitant is ethyl acetate, and the total volume ratio of the polyol solvent to the precipitant is 1:1 to 1:
5.
7. The method for preparing multinuclear magnetic ferrite nanoparticles according to claim 6, characterized in that, The metal precursor also includes one or more of cobalt acetylacetonate and nickel acetylacetonate.
8. A multinuclear magnetic ferrite nanoparticle, characterized in that, The nanoparticles were prepared using the method described in any one of claims 1-7.
9. An application of the multinuclear magnetic ferrite nanoparticles as described in claim 8 as a drug carrier.
10. The application of the multinuclear magnetic ferrite nanoparticles as described in claim 8 as a magnetic resonance imaging contrast agent.