Mn-doped MgAl-LDH particles for sonodynamic therapy and preparation and application of Mn-doped MgAl-LDH particles

Abstract

The invention discloses Mn-doped MgAl-LDH particles for sonodynamic therapy as well as preparation and application. The Mn-doped MgAl-LDH particles are synthesized through a chemical coprecipitation method, Mn ion doping under the protection of N2 and hydrothermal treatment. Wherein trace doping of Mn ions in an LDH structure causes an appropriate energy band structure, so that effective separation of electrons and holes under ultrasonic irradiation is promoted, and generation of ROS is promoted. The Mn-doped MgAl-LDH particles prepared by the preparation method disclosed by the invention show excellent SDT performance, can effectively inhibit the growth of tumors, and show good biocompatibility. Therefore, the innovative design of the invention opens up a potential path for exploring a novel sound-sensitive agent in effective ultrasonic catalytic tumor treatment.

Description

Technical Field

[0001] The invention belongs to the field of biological nanomaterials, and in particular relates to Mn-doped MgAl-LDH particles for sonodynamic therapy, and preparation and application thereof. Background Art

[0002] As a typical reactive oxygen species (ROS)-related treatment method, sonodynamic therapy (SDT) utilizes low-intensity ultrasound and rationally designed sonosensitizers to generate a large amount of toxic ROS, which leads to cell apoptosis. Based on the sonoluminescence caused by the ultrasonic cavitation effect, the sonosensitizer can be activated by ultrasound and absorb appropriate energy, resulting in the effective separation of electrons and holes. The activated electrons can react with the ambient oxygen at the tumor site to produce superoxide anions (·O 2- ), which can combine with the activated hole to subsequently generate toxic singlet oxygen ( 1 O2).

[0003] Sonosensitizers play a vital role in the SDT process. In the past few decades, significant progress has been made in the development of various high-efficiency sonosensitizers derived from photocatalysts, such as metal oxides, sulfides, and MOF / COF-based nanosensitizers. Among them, layered double hydroxides (LDHs) have been widely studied as a promising photocatalyst and catalyst support due to their abundant availability, excellent degradability, and unique layered structure.

[0004] As a hydrotalcite-like anionic clay, LDH is an inorganic layered nanomaterial composed of positively charged hydroxide layers stacked with edge-sharing octahedral M(OH)6 units and charge-balancing anions located between the layers. Notably, MgAl-LDH is a typical p-type semiconductor and is widely used in photocatalytic hydrogen and oxygen evolution reactions and water splitting. However, the photocatalytic activity of MgAl-LDH is limited by its weak light absorption and the rapid binding of activated electrons and holes.

[0005] In addition, LDH particles have good biosafety and biodegradability, which has good application prospects in vivo. However, precisely because of this, LDH will undergo structural collapse and gradual degradation in the weak acid environment of the tumor, not to mention its stable response performance under ultrasound, making it unable to play an effective role in ultrasound dynamic therapy. Summary of the invention

[0006] In view of the above problems, the present invention proposes a Mn-doped MgAl-LDH particle for sonodynamic therapy, preparation and application, which solves the problems of low photocatalytic activity and weak ROS generation ability of MgAl-LDH in the related art, and further uses it for tumor sonodynamic therapy to achieve efficient tumor inhibition. 2+ The trace doping in the LDH structure forms a suitable energy band structure, thereby promoting the effective separation of electrons and holes under ultrasonic irradiation, thereby promoting the generation of ROS. In addition, the MgAl-LDH crystal structure partially replaced by manganese is more stable and is not prone to structural collapse and degradation in a weak acid environment. The Mn-doped MgAl-LDH particles prepared by the present invention exhibit excellent SDT performance, can effectively inhibit tumor growth and exhibit good biocompatibility.

[0007] One of the technical solutions of the present invention is to provide a method for preparing the above-mentioned Mn-doped MgAl-LDH particles. The material is synthesized by a three-step process, a chemical coprecipitation method to prepare flaky MgAl-LDH, Mn ion doping under N2 protection and hydrothermal treatment. Specifically, the method comprises the following steps:

[0008] (1) Preparation of flaky MgAl-LDH;

[0009] (2) Mn ions are doped into MgAl-LDH to obtain Mn-doped MgAl-LDH.

[0010] Furthermore, the flaky MgAl-LDH is prepared by the following method:

[0011] MgCl2·6H2O and Al(NO3)3·9H2O in a molar ratio of 3:1 were dissolved in deionized water, then added to a 0.4M NaOH solution and stirred at room temperature for 20-40 minutes, wherein the molar ratio of MgCl2·6H2O to NaOH was 3:(6-8). The product was washed three to four times by centrifugation with water and redispersed in deionized water.

[0012] Furthermore, the Mn-doped MgAl-LDH is prepared by the following method:

[0013] 0.01M MnCl2·4H2O solution was added dropwise to 5-20mg / mL MgAl-LDH solution and stirred in N2 atmosphere, wherein the volume ratio of MnCl2·4H2O solution to MgAl-LDH solution was (3-10):20, and then transferred to a reactor and heated at 120-130°C for 16-20 h. After cooling to room temperature, the product was washed three to four times by centrifugation with water.

[0014] The second technical solution of the present invention is to provide a Mn-doped MgAl-LDH particle for sonodynamic therapy, wherein Mn 2+ Partially replace Mg in MgAl-LDH 2+ The nanoparticles are in the form of flakes with a particle size of 50-200nm.

[0015] The third technical solution of the present invention is to provide the above-mentioned nanoparticles as sonosensitizers for sonodynamic therapy and their application in sonodynamic therapy of tumors.

[0016] The Mn-doped MgAl-LDH particles prepared by the present invention have a smaller band gap than MgAl-LDH particles, and the doping of Mn leads to the formation of defect energy levels near the conduction band of MgAl-LDH, which can effectively capture activated electrons and inhibit electron-hole recombination, so that more activated electrons and holes can be activated under ultrasound to generate a large amount of ROS.

[0017] In vitro and in vivo experiments showed that Mn-doped MgAl-LDH particles exhibited excellent SDT performance, effectively inhibited tumor growth and showed good biocompatibility.

[0018] In addition, the present invention also relates to an ultrasound dynamic therapy system, comprising an ultrasound source and a sonosensitizer, wherein the sonosensitizer is the aforementioned Mn-doped MgAl-LDH particles. The ultrasound frequency is 1.0 MHz and the power is 1.0 W / cm 2 .

[0019] The beneficial effect of the present invention is that the trace doping of Mn ions in the Mn-doped MgAl-LDH particles synthesized by the present invention in the LDH structure leads to a suitable energy band structure, which promotes the effective separation of electrons and holes under ultrasonic irradiation, thereby promoting the generation of ROS. The Mn-doped MgAl-LDH particles synthesized by the present invention show good cell compatibility after being co-cultured with AML12 cells, and under the action of ultrasound, the Mn-doped MgAl-LDH particles show excellent SDT effect. In vivo anti-tumor experiments also show that the Mn-doped MgAl-LDH particles show excellent SDT treatment efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 is a SEM image of the MMA-LDH particles in Example 1;

[0021] Figure 2 TEM images of the MMA-LDH particles in Example 1 at different magnifications;

[0022] Figure 3 is the selected area electron diffraction pattern (SAED) of MMA-LDH in Example 1;

[0023] Figure 4 XRD patterns of MgAl-LDH particles and MMA-LDH in Example 1;

[0024] Figure 5 is the elemental spectrum of MMA-LDH in Example 1;

[0025] Figure 6 The hydrodynamic size distribution of MgAl-LDH particles and MMA-LDH in Example 1;

[0026] Figure 7 TEM images of MgAl-LDH after acid treatment for different time periods in Comparative Example 1;

[0027] Figure 8 Ultrasound (1.0 MHz, 1.0 W / cm 2 ) UV-Vis spectra of time-dependent degradation of DPBF after mixing with MgAl-LDH;

[0028] Fig. 9 Ultrasound (1.0 MHz, 1.0 W / cm 2 ) UV-Vis spectra of time-dependent degradation of DPBF after mixing with MMA-LDH under treatment;

[0029] Fig.10 is the degradation percentage of DPBF in MgAl-LDH and MMA-LDH solutions under ultrasonic treatment for different time;

[0030] Fig.11 For ultrasonic treatment (1.0 MHz, 1.0 W / cm 2 , 2 min) to detect the ESR spectrum of MMA-LDH 1 O2 production;

[0031] Fig.12 Electrochemical impedance spectra (EIS) of MgAl-LDH and MMA-LDH obtained by 5 mV AC signal;

[0032] Fig.13 (a) Solid diffuse reflectance spectra and (b) (αhν) of MgAl-LDH and MMA-LDH 2 The relationship curve between and h;

[0033] Fig.14 is the cell survival rate after co-culture of AML12 cells with different concentrations of MMA-LDH;

[0034] Fig.15is the survival rate of 4T1 cells after co-culture with different concentrations of MMA-LDH (0-100 μg / mL) for 24 h with or without ultrasonic treatment;

[0035] Fig.16 Fluorescence images of 4T1 cells after EdU and DAPI co-staining after different treatments (scale bar: 50 μm);

[0036] Fig.17 The clone formation of 4T1 cells after different treatments;

[0037] Fig.18 Fluorescence images of 4T1 cells stained with DCFH-DA after different treatments (scale bar: 50 μm);

[0038] Fig.19 Schematic diagram of SDT experiment on Balb / c mice;

[0039] Fig. 20 The weight changes of mice after different treatments;

[0040] Fig.21 The curves of tumor volume changes in mice after different treatments;

[0041] Fig. 22 The changes of tumor weights of mice after different treatments;

[0042] Fig.23 The tumor photos of mice in each treatment group on day 14;

[0043] Fig.24 H&E and Ki67 staining images of tumors removed from different treatment groups (day 14) (scale bar: 100 μm);

[0044] Fig.25 H&E staining images of the main organs of mice in different treatment groups were used for pathological examination (scale bar: 100 μm). DETAILED DESCRIPTION

[0045] The following examples are used to further illustrate the present invention, and their purpose is to illustrate the present invention and should not be construed as limiting the scope of the present invention. Unless otherwise specified, all parts by weight and weight percentages are used below.

[0046] The raw materials used in the present invention, unless otherwise specified, are conventional commercially available products; the methods used in the present invention, unless otherwise specified, are conventional methods in the art.

[0047] The embodiments of the present invention are further described below with reference to a plurality of embodiments.

[0048] It should be clear that the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present application.

[0049] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "said" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0050] Example 1

[0051] (1) MgCl2·6H2O (3 mmol) and Al(NO3)3·9H2O (1 mmol) were dissolved in deionized water (5 mL), and the mixed solution was then added to NaOH solution (15 mL, 0.4 M) and stirred at room temperature for 20 min. The product was washed three to four times by centrifugation with water and redispersed in deionized water to obtain a 5 mg / mL MgAl-LDH solution.

[0052] (2) MnCl2·4H2O solution (3 mL, 0.01 M) was added dropwise to 30 mL of the above MgAl-LDH solution and stirred overnight in a N2 atmosphere. Subsequently, the precursor solution was transferred to a 50 mL polytetrafluoroethylene reactor and heated at 120 °C for 16 h. After cooling to room temperature, the product was washed three times by centrifugation with water.

[0053] The SEM and TEM images of the materials obtained in step 1 and step 2 are shown in Figure 1 and Figure 2 ,It can be seen from the figure that the Mn-doped MgAl-LDH nanoparticles are flake-shaped with a size range of 50-200nm. Figure 3 and Figure 4 Shown are the selected area electron diffraction (SAED) and X-ray diffraction patterns, respectively, which analyze the crystallization characteristics and phase composition of MMA-LDH nanosheets. Figure 5 The elemental analysis results show that the Mn element is uniformly distributed in the MMA-LDH nanosheets. From the dynamic light scattering results ( Figure 6 ) As can be seen, the hydrodynamic size of MgAl-LDH is 270 nm, while that of MMA-LDH increases to 317 nm. The polydispersity indices of MgAl-LDH and MMA-LDH are ~0.208 and ~0.219, respectively.

[0054] Example 2

[0055] (1) MgCl2·6H2O (3 mmol) and Al(NO3)3·9H2O (1 mmol) were dissolved in deionized water (5 mL), and the mixed solution was then added to NaOH solution (20 mL, 0.4 M) and stirred at room temperature for 40 min. The product was washed three to four times by centrifugation with water and redispersed in deionized water to obtain a 20 mg / mL MgAl-LDH solution.

[0056] (2) MnCl2·4H2O solution (10 mL, 0.01 M) was added dropwise to 20 mL of the above MgAl-LDH solution and stirred overnight in a N2 atmosphere. Subsequently, the precursor solution was transferred to a 50 mL polytetrafluoroethylene reactor and heated at 130 °C for 20 h. After cooling to room temperature, the product was washed four times by centrifugation with water.

[0057] Embodiment 3:

[0058] The ROS types, characterization methods and results of Mn-doped MgAl-LDH particles are as follows:

[0059] In order to determine the type of ROS generated, the short-lived ROS were accurately captured using the spin trap TEMP. 1 O2 and ·OH. MMA-LDH solution (160 μL, 60 μg / mL) was mixed with TEMP or DMPO (40 μL) and treated with ultrasound for 2 min. TEMP- 1 O2 products. Fig.11 As shown, in the presence of MMA-LDH and ultrasound, the ESR spectrum exhibits three characteristic peaks with a ratio of 1:1:1, corresponding to TEMP- 1 O2 production, which indicates that ultrasound-induced 1 Production of O2.

[0060] Mechanism analysis: The charge transfer efficiency and carrier separation efficiency of MgAl-LDH and MMA-LDH were tested by electrochemical impedance spectroscopy (EIS). Fig.12 In the EIS Nyquist plot shown, MMA-LDH exhibits a smaller semicircle than MgAl-LDH, which indicates that MMA-LDH has lower charge resistance and higher conductivity. The results show that MMA-LDH has a higher separation efficiency of electrons and holes, which ultimately promotes the SDT performance of the material. In order to clarify the mechanism of the SDT performance of MMA-LDH, the energy band widths of MgAl-LDH and MMA-LDH were tested and calculated using solid diffuse reflectance spectroscopy. Fig.13 As shown in a, after doping Mn into MgAl-LDH, the light absorption ability of MMA-LDH is significantly enhanced. The band gap width is then calculated using the Tauc method. The results show that ( Fig.13b) The band gaps of MgAl-LDH and MMA-LDH are 3.61 eV and 2.52 eV, respectively, which indicates that the doping of Mn leads to a significant decrease in the energy band width, thus promoting the absorption of ultrasonic energy. In addition, the doping of Mn leads to the formation of defect levels near the conduction band of MgAl-LDH, which can effectively capture activated electrons and inhibit electron-hole recombination. Therefore, MMA-LDH can achieve more activation of activated electrons and holes under ultrasound to generate a large number of 1 O2.

[0061] Embodiment 4:

[0062] In vitro cell study of Mn-doped MgAl-LDH particles, the specific process and results are as follows:

[0063] AML12 mouse normal hepatocytes were used to evaluate the in vitro biocompatibility of MMA-LDH. Fig.14 As shown in the figure, MMA-LDH had no obvious toxicity to AML12 cells, and there was no statistical difference in cell survival rate after co-culture with MMA-LDH at a concentration of up to 100 ppm for 24 h, which indicated the good cell compatibility of MMA-LDH. The in vivo sonodynamic performance of MMA-LDH was studied by co-culturing 4T1 mouse breast cancer cells with MMA-LDH at different concentrations (0-100 ppm) and applying ultrasound treatment. Fig.15 As shown in the figure, after 24 h of co-culture with 4T1 cells, MMA-LDH was slightly toxic to 4T1 cells within a given concentration range, and ~75.2% of 4T1 cells survived at a concentration of 100 ppm. After ultrasound irradiation, MMA-LDH showed significantly enhanced cell killing ability, and the cell survival rate of 4T1 showed a concentration-dependent downward trend, and only 19% of the cells survived at a material concentration of 100 ppm, which shows the excellent SDT effect of MMA-LDH.

[0064] The phenomenon of inhibiting cell proliferation caused by the SDT effect of MMA-LDH was qualitatively studied through EdU staining experiments and clone formation experiments. 5-ethynyl-2'-deoxyuridine (EdU), as a thymidine analog, can replace thymidine and be incorporated into newly synthesized DNA during DNA synthesis. At the same time, the acetylene group on EdU can react with fluorescently labeled small molecule azide probes through Cu+ catalysis to produce a click reaction, thereby labeling newly synthesized DNA to detect proliferating cells. EdU / DAPI double staining results show that ( Fig.16), compared with the control group and the ultrasound group alone, the MMA-LDH treatment group showed slightly weakened green fluorescence, and after the combination of MMA-LDH and ultrasound treatment, the green fluorescence in the cells was significantly weakened, indicating that MMA-LDH+US treatment significantly reduced the proportion of EdU-stained cells. In addition, the results of clone formation also further showed that ( Fig.17 ), MMA-LDH+US treatment showed the strongest inhibitory effect on cell proliferation, which indicates that the combined treatment of MMA-LDH and US significantly inhibited the proliferation activity of 4T1 cells, which is consistent with the results of the MTT test. In addition, the generation of intracellular ROS during the SDT process was detected by the typical fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA). After DCFH-DA enters the cell, it can be cleaved by intracellular esterases and converted into DCF under the oxidation of ROS, emitting green fluorescence. Fig.18 As shown, the MMA-LDH+US combined treatment group showed the strongest green fluorescence intensity, while no obvious green fluorescence was detected in the cells of the control group, ultrasound alone group and MMA-LDH group, which indicates that MMA-LDH can produce a large amount of ROS under ultrasound and has a significant SDT effect.

[0065] Embodiment 5:

[0066] In vivo anti-tumor studies of Mn-doped MgAl-LDH particles are as follows:

[0067] Based on the excellent in vitro SDT effect of MMA-LDH, the antitumor activity of MMA-LDH was evaluated using the 4T1 breast cancer model. In vivo studies were conducted on tumor-bearing mice. The experimental process is as follows: Fig.19 The tumor-bearing mice were randomly divided into 4 groups (n = 5): (1) normal saline (control group, intravenous injection); (2) ultrasound alone group (1.0 MHz, 1.5 W / cm 2 , 2 minutes); (3) MMA-LDH (7.5 mg / kg, intravenous injection); (4) MMA-LDH+US (7.5 mg / kg, intravenous injection). The injection operation was repeated on days 0, 5, and 10, and ultrasound was performed on the corresponding groups 12 h and 24 h after injection ( Fig.19 The body weight and tumor volume of mice were tested and recorded every two days. Fig. 20 As shown in the figure, there was no significant difference in the body weight of mice in different groups during the entire treatment period, which means that MMA-LDH has good biosafety. MMA-LDH has a weak inhibitory effect on tumor growth, while the combined treatment of MMA-LDH and ultrasound showed an excellent tumor inhibition effect. The tumor inhibition rate of the MMA-LDH+US group can reach 72.6%, which is significantly higher than that of the other three groups ( Fig.21After treatment, the mice were killed and the tumors were removed, weighed and photographed. The results showed that ( Fig. 22 and Fig.23 ), the tumor weight and the photos of the resected tumors after treatment showed obvious differences, and the results were consistent with the tumor volume change curve, which also confirmed the excellent SDT treatment efficiency of MMA-LDH.

[0068] The SDT therapeutic effect of MMA-LDH was further investigated by H&E and Ki67 staining images of the resected tumors. Fig.24 As shown, compared with the other three groups, the MMA-LDH+US group showed obvious nuclear condensation and severe cytoplasmic vacuolation, which are typical apoptotic characteristics of tumor tissue. In addition, the Ki67 results proved that MMA-LDH combined with ultrasound treatment induced the most Ki67-positive cells, and the proliferation ability of 4T1 cells was significantly inhibited. The above two histochemical results are consistent with the results of the anti-tumor experiment. The biosafety of MMA-LDH was further evaluated by H&E staining of the main organs (heart, liver, spleen, lung and kidney) of mice in different groups after the treatment. The results showed that ( Fig.25 ), H&E staining images of major organs showed no obvious abnormalities, which demonstrated the biosafety of MMA-LDH and its potential for clinical application.

[0069] Comparative Example 1

[0070] MgCl2·6H2O (3 mmol) and Al(NO3)3·9H2O (1 mmol) were dissolved in deionized water (5 mL), and then the mixed solution was added to NaOH solution (15 mL, 0.4 M) and stirred at room temperature for 20 min. The product was washed three to four times by centrifugation with water and redispersed in 20 mL of deionized water to obtain MgAl-LDH solution.

[0071] Study on the stability of MgAl-LDH in acidic microenvironment: Figure 7 It can be seen that MgAl-LDH will degrade rapidly under acidic conditions, and the layered structure of LDH will collapse rapidly and cannot maintain a stable structure.

[0072] Study on ultrasonic response performance of MgAl-LDH and Mn-doped MgAl-LDH particles:

[0073] The ROS generation of MgAl-LDH and MMA-LDH under ultrasound irradiation was detected using a typical ROS probe DPBF. Specifically, DPBF (100 μL, 2 mmol / L) and MgAl-LDH or MMA-LDH (200 μL, 1 mg / mL) were added to an ethanol: water (1:1) mixture (2.7 mL). The solution was sonicated (1.0 MHz, 1.0 W / cm2) in the dark and the absorbance of the solution was detected every two minutes using a UV-Vis spectrophotometer. The SDT performance of different materials was compared by measuring the intensity at 415 nm, which represents the DPBF level.

[0074] The results are as follows Figure 8-10 As shown in the figure, under ultrasonic treatment, DPBF in the MgAl-LDH or MMA-LDH system gradually degraded over time. The degradation degree of DPBF induced by MgAl-LDH was low, while in the presence of MMA-LDH, the oxidation rate of DPBF was significantly accelerated, indicating that it has excellent SDT performance. The degradation rates of DPBF incubated with MgAl-LDH and MMA-LDH after ultrasonic treatment for 10 minutes were 41.28% and 73.93%, respectively, indicating that the doping of Mn enhanced the ultrasonic catalytic activity of MMA-LDH. The above results show that the ultrasonic response performance of MgAl-LDH without Mn doping is low, and the analysis mainly comes from two aspects: (1) MgAl-LDH has low photocatalytic activity and weak ability to generate ROS; (2) The structure of MgAl-LDH is easy to collapse under ultrasonic action and slightly acidic environment, and it cannot achieve effective ultrasonic dynamic effect. The crystal structure of MgAl-LDH partially replaced by manganese is not easily degraded in an acidic environment, and can maintain structural stability, achieving effective ultrasonic dynamic treatment effect.

[0075] The above embodiments describe in detail the structure, features and effects of the present invention. The above are only preferred embodiments of the present invention. Any changes made in accordance with the concept of the present invention, or modifications to equivalent embodiments with equivalent changes, which do not exceed the scope covered by the specification, should be within the protection scope of the present invention.

Claims

1. A method for preparing Mn-doped MgAl-LDH particles for sonodynamic therapy, characterized in that: The following steps are involved: (1) Preparation of flaky MgAl-LDH; (2) Mn ions are doped into MgAl-LDH to obtain Mn-doped MgAl-LDH.

2. The preparation method according to claim 1, characterized in that: The flaky MgAl-LDH is prepared by the following method: MgCl2·6H2O and Al(NO3)3·9H2O in a molar ratio of 3:1 were dissolved in deionized water, then added to a 0.4M NaOH solution and stirred at room temperature for 20-40 minutes, wherein the molar ratio of MgCl2·6H2O to NaOH was 3:(6-8). The product was washed three to four times by centrifugation with water and redispersed in deionized water.

3. The preparation method according to claim 1, characterized in that: The Mn-doped MgAl-LDH is prepared by the following method: A 0.01 M MnCl2·4H2O solution was added dropwise to a 5-20 mg / mL MgAl-LDH solution and stirred in a N2 atmosphere, wherein the volume ratio of the MnCl2·4H2O solution to the MgAl-LDH solution was (3-10):(20-30), and then transferred to a reactor and heated at 120-130°C for 16-20 h; after cooling to room temperature, the product was washed three to four times by centrifugation with water.

4. A Mn-doped MgAl-LDH particle for sonodynamic therapy, characterized in that: Mn 2+ Partially replace Mg in MgAl-LDH 2+ The location.

5. The particle according to claim 4, characterized in that The nanoparticles are flake-shaped and have a particle size of 50-200nm.

6. Use of the Mn-doped MgAl-LDH particles as claimed in any one of claims 1 to 5 as sonosensitizers in sonodynamic therapy for tumors.

7. An ultrasonic dynamic therapy system, characterized in that: The method comprises an ultrasonic source and a sonosensitizer, wherein the sonosensitizer comprises Mn-doped MgAl-LDH particles prepared by the method according to claim 1.

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