Asymmetric magnetic nanoparticles, their preparation method and applications

Abstract

This invention discloses an asymmetric magnetic nanoparticle, its preparation method, and its applications. The asymmetric magnetic nanoparticle comprises, from the inside out, an Er-doped NaYF4 core, a NaYF4 layer, and an asymmetric mesoporous silica layer, with Fe2C nanoparticles loaded on the asymmetric mesoporous silica layer. The asymmetric magnetic nanoparticle of this invention possesses advantages such as enabling remote and precise navigation, efficient and stable enrichment in target areas, and long-term high-contrast afterglow emission. It can not only improve the safety and effectiveness of malignant tumor treatment but also achieve integrated and visualized diagnosis and treatment processes, making it suitable for large-scale industrial applications.

Description

Technical Field

[0001] This invention relates to the field of targeted drug delivery technology, specifically to an asymmetric magnetic nanoparticle, its preparation method, and its application. Background Technology

[0002] Malignant tumors (also known as cancer) are caused by the malignant proliferation of cells. They are invasive and metastatic, and are one of the major diseases that seriously threaten human health. Chemotherapy is a core treatment for malignant tumors, but traditional chemotherapy methods have significant drawbacks, specifically: Traditional chemotherapy uses systemic administration, resulting in low drug accumulation efficiency at the lesion site. To achieve effective therapeutic concentrations, the dosage must be increased, inevitably damaging healthy tissues and organs and causing severe toxic side effects. Therefore, traditional chemotherapy methods not only have limited efficacy but also reduce the patient's quality of life.

[0003] Magnetic targeted drug delivery systems are a special targeting technology that uses an external magnetic field to guide and enrich drug-loaded magnetic particles to the lesion site. Its core advantage lies in its remote, real-time, and controllable targeting capabilities, which can reduce systemic exposure and increase drug concentration at the target site. However, existing magnetic targeted drug delivery systems still have significant drawbacks and cannot fully meet practical application requirements, specifically: 1) Insufficient navigation accuracy: Static magnetic fields cannot provide complex and precise real-time navigation for high-speed moving nanocarriers in the blood. Nanocarriers mainly rely on passive transport by blood flow to the vicinity of the target area where they are captured by the magnetic field, resulting in very limited active targeting capabilities for deep tissues or lesions; 2) Limited enrichment efficiency: As the distance between the external magnetic field and the lesion site increases, the magnetic field strength and gradient decrease sharply, significantly weakening the magnetic force acting on the nanocarrier. The nanocarrier struggles to overcome the scouring force of blood flow, leading to a large number of nanocarriers "off-target" and unsatisfactory enrichment efficiency; 3) Limited functionality: Most traditional magnetic carriers are passively responding particles to magnetic fields, lacking autonomous movement capabilities and unable to achieve complex functions such as actively crossing biological barriers and penetrating deep tissues.

[0004] Therefore, it is of great significance to develop a magnetically targeted drug delivery material that can achieve remote and precise navigation and can be efficiently and stably enriched in the target area. Summary of the Invention

[0005] The purpose of this invention is to provide an asymmetric magnetic nanoparticle, its preparation method, and its application.

[0006] The technical solution adopted in this invention is: An asymmetric magnetic nanoparticle comprises, from the inside out, an Er-doped NaYF4 core, a NaYF4 layer, and an asymmetric mesoporous silica layer, wherein the asymmetric mesoporous silica layer is loaded with Fe2C nanoparticles.

[0007] Preferably, the Er doping amount of the Er-doped NaYF4 core is 2.8 mmol% to 3.2 mmol.

[0008] Preferably, the diameter of the Er-doped NaYF4 core is 23 nm to 30 nm.

[0009] Preferably, the thickness of the NaYF4 layer is 25nm to 37nm.

[0010] Preferably, the asymmetric mesoporous silica layer has a feather-shaped profile.

[0011] Preferably, the thickness of the asymmetric mesoporous silica layer is 193 nm to 200 nm.

[0012] Preferably, the Fe2C nanoparticles have a particle size of 1 nm to 3 nm.

[0013] A method for preparing asymmetric magnetic nanoparticles as described above includes the following steps: 1) A methanol solution of YCl3, ErCl3, oleic acid, octadecene, and NH4F-NaOH is mixed and reacted to obtain NaYF4:Er; 2) Mix NaYF4:Er and NH4F-NaOH methanol solutions and react to obtain NaYF4:Er@NaYF4; 3) Disperse NaYF4:Er@NaYF4 in a mixed solution of ethanol, water and ammonia, then add tetraethyl orthosilicate for hydrolysis to obtain NaYF4:Er@NaYF4@nSiO2; 4) Disperse NaYF4:Er@NaYF4@nSiO2 and triethylamine in water, then add hexadecyltrimethylammonium chloride and mix evenly. Then add chlorobenzene and tetraethyl orthosilicate for hydrolysis to obtain NaYF4:Er@NaYF4@nSiO2-mSiO2. 5) NaYF4:Er@NaYF4@nSiO2-mSiO2, octadecene, oleylamine and ammonium bromide were mixed, and then iron pentacarbonyl was added for reaction. Oleic acid was then added, and the product was separated and purified to obtain asymmetric magnetic nanoparticles.

[0014] Preferably, the molar ratio of YCl3 and ErCl3 in step 1) is 1:0.02 to 0.04.

[0015] Preferably, the reaction in step 1) is carried out at a temperature of 145℃ to 155℃ for a reaction time of 50 min to 70 min.

[0016] Preferably, the reaction in step 2) is carried out at a temperature of 280℃ to 300℃ for a reaction time of 80 min to 100 min.

[0017] Preferably, in step 3), the mass ratio of NaYF4:Er@NaYF4 to tetraethyl orthosilicate is 1:12-14.

[0018] Preferably, the hydrolysis in step 3) is carried out at a temperature of 30℃ to 40℃ for a time of 12h to 24h.

[0019] Preferably, in step 4), the mass ratio of NaYF4:Er@NaYF4@nSiO2 to tetraethyl orthosilicate is 1:30-40.

[0020] Preferably, the hydrolysis in step 4) is carried out at a temperature of 50℃ to 70℃ for a time of 10h to 15h.

[0021] Preferably, in step 5), the mass ratio of NaYF4:Er@NaYF4@nSiO2-mSiO2 to iron pentacarbonyl is 1:10 to 20.

[0022] Preferably, the reaction in step 5) is carried out at a temperature of 170℃ to 190℃ for a reaction time of 20 min to 40 min.

[0023] A targeted drug comprising the aforementioned asymmetric magnetic nanoparticles.

[0024] The beneficial effects of this invention are: the asymmetric magnetic nanoparticles of this invention have the advantages of enabling remote and precise navigation, efficient and stable enrichment in the target area, and long-term high-contrast afterglow emission. They can not only improve the safety and effectiveness of malignant tumor treatment, but also realize the integration and visualization of the diagnosis and treatment process, making them suitable for large-scale industrial applications.

[0025] Specifically: 1) The asymmetric magnetic nanoparticles of the present invention have the characteristics of X-ray excitation and near-infrared long afterglow emission, with an afterglow time of up to several hours, which can realize the integration and visualization of the diagnosis and treatment process of malignant tumors. 2) The imaging mode of the asymmetric magnetic nanoparticles of the present invention can effectively avoid the interference of autofluorescence of biological tissues, thereby enabling high-contrast imaging of organs and continuous emission imaging of the NIR-II region of tumors. 3) The asymmetric magnetic nanoparticles of the present invention can generate effective autonomous propulsion under the drive of an external vortex magnetic field, which significantly improves their mobility and navigation accuracy in complex biological fluids (e.g., blood). 4) The active movement of the asymmetric magnetic nanoparticles of the present invention can be combined with the anchoring effect of the gradient magnetic field generated by the injectable magnetic hydrogel (which can form a stable, durable and spatially controllable local gradient magnetic field by pre-implanting in the lesion area), thereby achieving synergistic enhanced targeting from large-scale precise navigation to local stable retention in the lesion, and completely solving the problem of low efficiency of traditional passive targeting strategies. Attached Figure Description

[0026] Figure 1 The images show SEM images and particle size distribution diagrams of NaYF4:3%Er and NaYF4:3%Er@NaYF4 with different diameters in the examples.

[0027] Figure 2 The images shown are TEM and EDS spectra of NaYF4:3%Er@NaYF4@nSiO2-mSiO2 and NYF@nm-Fe in the examples.

[0028] Figure 3 The image shows the XRD pattern of NaYF4:3%Er@NaYF4 in the example.

[0029] Figure 4 The XRD patterns of NaYF4:3%Er@NaYF4@nSiO2-mSiO2 and NYF@nm-Fe in the examples are shown.

[0030] Figure 5 The image shows the XPS full spectrum of NYF@nm-Fe in the example.

[0031] Figure 6 The fine XPS spectrum of Fe 2p for NYF@nm-Fe in the examples is shown.

[0032] Figure 7 The nitrogen adsorption-desorption isotherm curves of NaYF4:3%Er@NaYF4@nSiO2-mSiO2 in the examples are shown.

[0033] Figure 8 The nitrogen adsorption-desorption isotherm curves for NYF@nm-Fe in the examples are shown.

[0034] Figure 9 The fluorescence spectra of NaYF4:3%Er and NaYF4:3%Er@NaYF4 with different diameters are shown in the examples.

[0035] Figure 10 This is the hysteresis loop of NYF@nm-Fe in the example.

[0036] Figure 11 The hysteresis loop of samarium iron nitrogen rare earth permanent magnet material.

[0037] Figure 12 It is the hysteresis loop of an injectable magnetic hydrogel.

[0038] Figure 13 This is a magnetic field propagation diagram of NYF@nm-Fe in the embodiment.

[0039] Figure 14 The diagram shows the relationship between the movement of the vortex cluster formed by NYF@nm-Fe in the embodiment and the magnetic field strength.

[0040] Figure 15 This is a CT image of an isolated tumor. Detailed Implementation

[0041] The present invention will be further explained and described below with reference to specific embodiments.

[0042] Example: An asymmetric magnetic nanoparticle, the preparation method of which is as follows: 1) Preparation of NaYF4:3%Er with different diameters: a) Mix 0.0582 mmol of YCl3, 0.0018 mmol of ErCl3, 3 mL of oleic acid, 7 mL of octadecene, and 25 mL of a methanol solution of NH4F-NaOH (NH4F concentration of 8 mmol / L and NaOH concentration of 20 mmol / L) thoroughly, stir at 150 °C for 1 h, then stir and cool to room temperature, and finally stir at 50 °C for 70 min to obtain NaYF4:3%Er (diameter of approximately 18 nm; dispersion). b) Mix 3 mL of the NaYF4:3%Er (dispersion) obtained in step a), 0.0582 mmol of YCl3, 0.0018 mmol of ErCl3, 3 mL of oleic acid, 7 mL of octadecene, and 25 mL of a methanol solution of NH4F-NaOH (NH4F concentration of 8 mmol / L and NaOH concentration of 20 mmol / L) thoroughly, stir at 150 °C for 1 h, then stir and cool to room temperature, and finally stir at 50 °C for 70 min to obtain NaYF4:3%Er (diameter approximately 26.5 nm; dispersion). 2) Preparation of NaYF4:3%Er@NaYF4 with different diameters: i) Mix the NaYF4:3%Er (approximately 26.5 nm in diameter; dispersion) obtained in step 1) with 25 mL of a methanol solution of NH4F-NaOH (NH4F concentration of 8 mmol / L, NaOH concentration of 20 mmol / L), stir for 40 min, then place in an open reactor and stir at 100 °C for 7 min. After sealing the reactor, continue stirring for 30 min, then ventilate for 10 s and evacuate for 10 min. Repeat this process 3 times until the bubbles disappear. After ventilating again, raise the temperature to 290 °C and stir for 90 min. Allow to cool naturally to room temperature, then add ethanol and centrifuge to obtain NaYF4:3%Er@NaYF4 (approximately 33 nm in diameter, abbreviated as NYF; dispersion). ii) Mix the NaYF4:3%Er@NaYF4 (dispersion) obtained in step i) with 25 mL of NH4F-NaOH methanol solution (NH4F concentration of 8 mmol / L, NaOH concentration of 20 mmol / L), stir for 40 min, then place in an open reactor and stir at 100 °C for 7 min. After sealing the reactor, continue stirring for 30 min, then ventilate for 10 s and evacuate for 10 min. Repeat this process 3 times until the bubbles disappear. After ventilating again, raise the temperature to 290 °C and stir for 90 min. Allow to cool naturally to room temperature, then add ethanol and centrifuge to obtain NaYF4:3%Er@NaYF4 (diameter approximately 53 nm, abbreviated as NYF; dispersion). 3) Disperse 1 mL of NaYF4:3%Er@NaYF4 (approximately 53 nm in diameter; dispersion) in a mixed solution consisting of 100 mL of ethanol, 7.6 mL of deionized water, and 4.0 mL of ammonia (10% by mass). Add 5.6 mL of tetraethyl orthosilicate, stir at 35 °C for 12 h, centrifuge, wash the solid with ethanol and deionized water, and dry at 60 °C overnight to obtain NaYF4:3%Er@NaYF4@nSiO2. 4) Add 60 mg of NaYF4:3%Er@NaYF4@nSiO2 and 0.035 g of triethylamine to 6 mL of deionized water, sonicate for 15 min, then add 4 mL of 98% hexadecyltrimethylammonium chloride aqueous solution, stir at 60 °C for 1 h, add 8.75 mL of chlorobenzene and 2.25 mL of tetraethyl orthosilicate, continue stirring at 60 °C for 12 h, centrifuge, take the solid and wash with ethanol and deionized water, then dry at 50 °C overnight to obtain NaYF4:3%Er@NaYF4@nSiO2-mSiO2; 5) Mix 60 mg of NaYF4:3%Er@NaYF4@nSiO2-mSiO2, 3 mL of octadecene, 5 mL of oleylamine and 0.5 g of ammonium bromide, stir at 80 °C for 1 h, then heat to 180 °C and slowly add 1 mL of 90% (w / w) iron pentacarbonyl aqueous solution. After the addition is complete, keep warm for 30 min, then cool to 140 °C and add 0.4 mL of oleic acid. Cool to room temperature and then centrifuge with acetone to obtain asymmetric magnetic nanoparticles (denoted as NYF@nm-Fe).

[0043] Performance testing: 1) Scanning electron microscope (SEM) images and particle size distribution diagrams of NaYF4:3%Er and NaYF4:3%Er@NaYF4 with different diameters in the examples are shown below. Figure 1 As shown (a-d are SEM images, e-h are particle size distribution images).

[0044] Depend on Figure 1 It can be seen that two types of NaYF4:3%Er with diameters of approximately 18 nm and 26.5 nm, and two types of NaYF4:3%Er@NaYF4 with diameters of approximately 33 nm and 53 nm were prepared.

[0045] 2) Transmission electron microscopy (TEM) images and EDS spectra of NaYF4:3%Er@NaYF4@nSiO2-mSiO2 and NYF@nm-Fe in the examples are as follows: Figure 2 (a is the TEM image of NaYF4:3%Er@NaYF4@nSiO2-mSiO2, b is the TEM image of NYF@nm-Fe, and c is the EDS spectrum of YF@nm-Fe.)

[0046] Depend on Figure 2 It can be seen that NYF@nm-Fe was successfully synthesized. It has an asymmetric morphology and a badminton-like shape, which is beneficial for subsequent magnetic manipulation.

[0047] 3) The X-ray diffraction (XRD) pattern of NaYF4:3%Er@NaYF4 (approximately 53 nm in diameter) in the embodiment is shown below. Figure 3 As shown.

[0048] Depend on Figure 3 It can be seen that NaYF4:3%Er@NaYF4 is a pure hexagonal crystal phase, which corresponds one-to-one with the standard card and has good crystallinity.

[0049] 4) The XRD patterns of NaYF4:3%Er@NaYF4@nSiO2-mSiO2 and NYF@nm-Fe in the examples are as follows: Figure 4 As shown.

[0050] Depend on Figure 4 It can be seen that NaYF4:3%Er@NaYF4@nSiO2-mSiO2 contains an amorphous silicon dioxide structure, while NYF@nm-Fe successfully introduces Fe with a crystalline structure.

[0051] 5) The XPS (X-ray photoelectron spectroscopy) full spectrum of NYF@nm-Fe in the examples is as follows: Figure 5 As shown.

[0052] Depend on Figure 5 It can be seen that NYF@nm-Fe contains Fe, Si and O elements, indicating that it was successfully prepared.

[0053] 6) The fine XPS spectrum of Fe 2p of NYF@nm-Fe in the examples is shown below. Figure 6 As shown.

[0054] Depend on Figure 6 It can be seen that the iron element in NYF@nm-Fe is in the form of Fe. 3+ Main, Fe 2+ It exists in a mixed valence state as a secondary form.

[0055] 7) The nitrogen adsorption-desorption isotherm curves of NaYF4:3%Er@NaYF4@nSiO2-mSiO2 in the examples are as follows: Figure 7 As shown.

[0056] Depend on Figure 7 It can be seen that NaYF4:3%Er@NaYF4@nSiO2-mSiO2 has a high specific surface area (200m²). 2 The well-developed mesoporous structure ( / g) is conducive to the subsequent adsorption and growth of crystalline iron on its surface.

[0057] 8) The nitrogen adsorption-desorption isotherm curves of NYF@nm-Fe in the examples are as follows: Figure 8 As shown.

[0058] Depend on Figure 8 It can be seen that the specific surface area of ​​NYF@nm-Fe is reduced to only 75m². 2 / g indicates that Fe2C was successfully grown on its surface.

[0059] 9) The fluorescence spectra of NaYF4:3%Er and NaYF4:3%Er@NaYF4 with different diameters in the examples are shown below. Figure 9 As shown.

[0060] Depend on Figure 9 It can be seen that as the particle size increases, the intensity of near-infrared fluorescence excited by X-rays gradually increases.

[0061] 10) The hysteresis loop of NYF@nm-Fe in the embodiment is as follows: Figure 10 As shown.

[0062] Depend on Figure 10 It can be seen that NYF@nm-Fe exhibits superparamagnetic characteristics, with a saturation magnetization of about 40 emu / g, extremely low coercivity (close to zero), and negligible remanence.

[0063] 11) The hysteresis loop of samarium iron nitrogen (SmFeN) rare earth permanent magnet materials is as follows: Figure 11 As shown.

[0064] Depend on Figure 11 It can be seen that SmFeN exhibits ferromagnetic characteristics, with a hysteresis loop showing typical hard magnetic properties, high saturation magnetization (approximately 150 emu / g), and significant coercivity.

[0065] 12) Preparation of injectable magnetic hydrogels: a) Disperse 30 mg of hyaluronic acid and 30 mg of cyclodextrin in 0.95 mL of PBS buffer, add 50 μL of 0.5% LAP photoinitiator aqueous solution, and irradiate with UV for 5 min to obtain hydrogel; b) Mix 1 mL of hydrogel and 50 mg of samarium iron nitrogen (SmFeN) rare earth permanent magnet material evenly to obtain an injectable magnetic hydrogel.

[0066] Hysteresis loop of injectable magnetic hydrogels, such as Figure 12 (The illustration in the lower right corner is a picture of the actual injectable magnetic hydrogel.)

[0067] Depend on Figure 12 It can be seen that the hysteresis loop is a narrow "S" shape and closes through the origin, with a saturation magnetization of about 80 emu / g. At the same time, the coercivity and remanence are close to zero, indicating that the injectable magnetic hydrogel exhibits typical superparamagnetism at room temperature. This means that despite the introduction of the hydrogel organic network, the NFeSm nanoparticles in it still maintain their nanoscale crystal characteristics, giving the injectable magnetic hydrogel both good magnetic responsiveness and no remanence. This injectable magnetic hydrogel can be used to precisely navigate asymmetric magnetic nanoparticles to the lesion site (by pre-implanting the injectable magnetic hydrogel in the lesion area to form a stable, durable, and spatially controllable local gradient magnetic field).

[0068] 13) The NYF@nm-Fe in the examples was observed under a microscope by controlling the type and parameters of the magnetic field, and the resulting trajectory diagram is shown below. Figure 13 As shown.

[0069] Depend on Figure 13It can be seen that as the magnetic field strength increases from 0 mT to 8 mT, the aspect ratio of the cluster gradually increases from the initial state to 2.4, and reaches a maximum value at a certain strength, and then gradually decreases. Under a lower magnetic field, the magnetic torque is insufficient to drive all units to form a highly oriented structure. A moderate magnetic field can achieve optimal oriented arrangement and vortex coordinated motion, which is manifested as the maximum aspect ratio. An excessively strong magnetic field may lead to motion instability or excessive aggregation, thereby reducing shape anisotropy.

[0070] 14) The NYF@nm-Fe in the embodiment was observed under a microscope by controlling the type and parameters of the magnetic field. The resulting graph shows the relationship between the movement of the vortex cluster and the magnetic field strength. Figure 14 As shown.

[0071] Depend on Figure 14 It can be seen that by adjusting the type and parameters of the magnetic field, the motion behavior and trajectory of the NYF@nm-Fe cluster can be precisely controlled; by controlling the rotation frequency and intensity of the magnetic field, the NYF@nm-Fe cluster can be guided to move along a specific trajectory, indicating that NYF@nm-Fe has good maneuverability, and its response speed increases with the increase of magnetic field strength and frequency, showing a high magnetic responsivity.

[0072] 15) Injectable magnetic hydrogel (as above) was injected into mouse tumors, followed by NYF@nm-Fe from the previous example injected via the tail vein. Mice were sacrificed at different time points (0h, 12h, and 24h), and the tumors were dissected. CT images of the ex vivo tumors are shown below. Figure 15 As shown.

[0073] Depend on Figure 15 It can be seen that NYF@nm-Fe exhibits significant enrichment and retention at the tumor site over time, indicating that the combination of the active movement of asymmetric magnetic nanoparticles and the anchoring effect of the gradient magnetic field generated by the injectable magnetic hydrogel can achieve synergistic enhanced targeting from large-scale precise navigation to local stable retention of lesions, ultimately completely solving the problem of low efficiency in traditional passive targeting strategies.

[0074] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. An asymmetric magnetic nanoparticle, characterized in that, From the inside out, it consists of an Er-doped NaYF4 core, a NaYF4 layer, and an asymmetric mesoporous silica layer, with the asymmetric mesoporous silica layer loaded with Fe2C nanoparticles.

2. The asymmetric magnetic nanoparticle of claim 1, wherein: The Er doping amount of the Er-doped NaYF4 core is 2.8 mmol% to 3.2 mmol.

3. The asymmetric magnetic nanoparticle of claim 1, wherein: The asymmetric mesoporous silica layer has a feather-like shape.

4. The asymmetric magnetic nanoparticle according to any one of claims 1 to 3, wherein: The Er-doped NaYF4 core has a diameter of 23 nm to 30 nm; the NaYF4 layer has a thickness of 25 nm to 37 nm; the asymmetric mesoporous silica layer has a thickness of 193 nm to 200 nm; and the Fe2C nanoparticles have a particle size of 1 nm to 3 nm.

5. A method for preparing asymmetric magnetic nanoparticles as described in any one of claims 1 to 4, characterized in that, Includes the following steps: 1) A methanol solution of YCl3, ErCl3, oleic acid, octadecene, and NH4F-NaOH is mixed and reacted to obtain NaYF4:Er; 2) Mix NaYF4:Er and NH4F-NaOH methanol solutions and react to obtain NaYF4:Er@NaYF4; 3) Disperse NaYF4:Er@NaYF4 in a mixed solution of ethanol, water and ammonia, then add tetraethyl orthosilicate for hydrolysis to obtain NaYF4:Er@NaYF4@nSiO2; 4) Disperse NaYF4:Er@NaYF4@nSiO2 and triethylamine in water, then add hexadecyltrimethylammonium chloride and mix evenly. Then add chlorobenzene and tetraethyl orthosilicate for hydrolysis to obtain NaYF4:Er@NaYF4@nSiO2-mSiO2. 5) NaYF4:Er@NaYF4@nSiO2-mSiO2, octadecene, oleylamine and ammonium bromide were mixed, and then iron pentacarbonyl was added for reaction. Oleic acid was then added, and the product was separated and purified to obtain asymmetric magnetic nanoparticles.

6. The method for preparing asymmetric magnetic nanoparticles according to claim 5, characterized in that: Step 1) The molar ratio of YCl3 and ErCl3 is 1:0.02 to 0.04; Step 1) The reaction is carried out at a temperature of 145℃ to 155℃ for a reaction time of 50 min to 70 min; Step 2) The reaction is carried out at a temperature of 280℃ to 300℃ for a reaction time of 80 min to 100 min.

7. The method for preparing asymmetric magnetic nanoparticles according to claim 5, characterized in that: In step 3), the mass ratio of NaYF4:Er@NaYF4 to tetraethyl orthosilicate is 1:12-14; the hydrolysis in step 3) is carried out at a temperature of 30℃-40℃ for 12h-24h.

8. The method for preparing asymmetric magnetic nanoparticles according to claim 5, characterized in that: Step 4) The mass ratio of NaYF4:Er@NaYF4@nSiO2 to tetraethyl orthosilicate is 1:30-40; Step 4) The hydrolysis is carried out at a temperature of 50℃-70℃ for 10-15 hours.

9. The method for preparing asymmetric magnetic nanoparticles according to claim 5, characterized in that: Step 5) The mass ratio of NaYF4:Er@NaYF4@nSiO2-mSiO2 to iron pentacarbonyl is 1:10-20; Step 5) The reaction is carried out at a temperature of 170℃-190℃ for a reaction time of 20min-40min.

10. A targeted drug, characterized in that, It includes the asymmetric magnetic nanoparticles as described in any one of claims 1 to 4.

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