WO2022217871A1

WO2022217871A1 - Bismuth/barium titanate heterojunction for enhancing sonodynamic antitumor effect and preparation method therefor

Info

Publication number: WO2022217871A1
Application number: PCT/CN2021/123500
Authority: WO
Inventors: 宁成云; 杨虹; 翟锦霞; 肖才榕; 于鹏; 李扬帆; 周正难; 张欢
Original assignee: 华南理工大学
Priority date: 2021-04-12
Filing date: 2021-10-13
Publication date: 2022-10-20
Also published as: CN113209290A; CN113209290B

Abstract

Disclosed in the present invention are a bismuth/barium titanate heterojunction for enhancing a sonodynamic antitumor effect and a preparation method therefor. The method of the present invention comprises: (1) preparing barium titanate nanoparticles by means of a hydrothermal method; (2) performing high-temperature and high-pressure polarization treatment on the barium titanate nanoparticles; and (3) depositing bismuth on the surface of the barium titanate nanoparticles by using a one-step in-situ deposition method, and constructing a bismuth/barium titanate P-N heterojunction. The bismuth/barium titanate heterojunction of the present invention has good biocompatibility, high safety, and good stability, and can enhance a sonodynamic antitumor effect.

Description

A kind of bismuth/barium titanate heterojunction with enhanced sonodynamic anti-tumor and preparation method thereof

technical field

The invention belongs to the technical field of nanomaterials for sonodynamic therapy of tumors, in particular to a bismuth/barium titanate heterojunction capable of enhancing sonodynamic anti-tumor and a preparation method thereof.

Background technique

Breast cancer seriously threatens the life and health of human beings, especially women. The current clinical treatments for breast cancer mainly revolve around surgical resection, chemotherapy and radiotherapy. Surgical removal of the breast is usually the preferred treatment for breast cancer, but incomplete removal can lead to cancer metastasis and cancer recurrence. Chemotherapy and radiotherapy are often used as adjuvant methods to remove small lesions, but the side effects will obviously lead to immunocompromised patients or poor treatment effect. Sonodynamic therapy (SDT) is a non-invasive, harmless and precise treatment method. The therapy uses ultrasound to activate sonosensitizers to generate reactive oxygen species (ROS) to kill cancer cells, which can only target cancer cells without damaging surrounding areas. Normal cells or organs can also avoid the side effects caused by traditional tumor treatments. In addition, the penetration depth of ultrasound in human tissue can reach 10cm, which can be used to treat deep tumors.

Barium titanate has piezoelectricity, because the built-in electric field constructed under ultrasound can promote the separation of electron-hole pairs and enhance the generation of reactive oxygen species, and is currently mainly used in the field of catalysis. In addition, studies have shown that noble metal deposition can further enhance the separation of electron-hole pairs and increase the production of reactive oxygen species. According to reports, bismuth metal has good biocompatibility, and compared with precious metals such as platinum and gold, bismuth is inexpensive, abundant in resources, environmentally friendly, and has good optical and electrical properties, which can replace platinum and gold. and other precious metals. At present, nano-scale bismuth is mainly obtained by electrochemical deposition, and bismuth is plated on three-dimensional cathode materials by electroplating. However, this method is only suitable for three-dimensional materials and is ineffective for loading bismuth on the surface of nanomaterials. In addition, the electrochemical deposition method is complicated and the coating It is not uniform and not friendly to the environment. It is necessary to explore new methods to enable bismuth element to be uniformly deposited on the surface of nanomaterials.

SUMMARY OF THE INVENTION

In order to solve the shortcomings and deficiencies of the prior art, the primary purpose of the present invention is to provide a preparation method of a bismuth/barium titanate heterojunction that enhances acoustic dynamics and anti-tumor.

First, the barium titanate piezoelectric nanoparticles were synthesized by hydrothermal treatment, then the barium titanate nanoparticles were polarized by high temperature and high pressure polarization, and then bismuth element was loaded on the surface of the barium titanate piezoelectric nanoparticles by one-step in-situ deposition method. , forming a bismuth/barium titanate heterojunction.

Another object of the present invention is to provide a bismuth/barium titanate heterojunction with enhanced sonodynamic anti-tumor prepared by the above method.

The bismuth/barium titanate heterojunction obtained by the invention can enhance the curative effect of sonodynamic therapy by combining with non-invasive ultrasound to generate reactive oxygen species with low tumor cell tolerance.

The object of the present invention is achieved through the following technical solutions:

A preparation method of a bismuth/barium titanate heterojunction with enhanced acoustic power and anti-tumor, comprising the following steps:

(1) drip ammonia water into the tetrabutyl titanate solution, add it to the octahydrate barium hydroxide solution after mixing, add ethanolamine dropwise after mixing, then hydrothermally react, centrifugally wash, and dry to obtain a nanometer barium titanate particles;

(2) carrying out high temperature and high pressure polarization treatment on the barium titanate nanoparticles to obtain polarized barium titanate nanoparticles;

(3) adding polarized barium titanate nanoparticles into the bismuth nitrate pentahydrate solution, after mixing uniformly, adding sodium borohydride for reaction, centrifugal washing, and drying to obtain a bismuth/barium titanate heterojunction.

Preferably, the concentration of the tetrabutyl titanate solution in step (1) is 0.8-2 mol/L, and the solvent is absolute ethanol, which is dissolved at room temperature; the concentration of the barium hydroxide octahydrate solution is 1-2 mol/L, The solvent is deionized water, and the dissolution temperature is 80-100°C.

Preferably, in step (1), the molar ratio of tetrabutyl titanate, ammonia water, sodium hydroxide octahydrate and ethanolamine is 1:2.8:1.3:2～1:3.8:1.5:2.8.

Preferably, the dripping speed of the ammonia water in step (1) is 0.5-1 mL/min; the dripping speed of the ethanolamine is 0.5-1 mL/min.

Preferably, in step (1), ammonia water and ethanolamine are added dropwise and then stirred for 10-30 min each.

Preferably, the temperature of the hydrothermal reaction in step (1) is 180-210° C., and the time is 42-54 h.

Preferably, the centrifugal washing in step (1) refers to alternating centrifugal washing with absolute ethanol and deionized water for 3 to 5 times, wherein the centrifugal speed is 7000 to 9000 rpm, and the time is 5 to 10 min; the drying refers to Dry at 50～70℃.

Preferably, the parameters of the high temperature and high pressure polarization treatment in step (2) are: the polarization temperature is 90-110° C., the polarization electric field intensity is 2-4 KV/cm, and the polarization time is 5-15 minutes.

Preferably, in step (3), the molar ratio of bismuth nitrate pentahydrate, polarized barium titanate nanoparticles and sodium borohydride is 1:5.7:5-1:8.6:15.

Preferably, the solvent of the bismuth nitrate pentahydrate solution in step (3) is deionized water, wherein the concentration of polarized barium titanate nanoparticles is 5-10 mg/mL, the bismuth nitrate pentahydrate is 2.5-7.5 mmol/L, and the hydrogen borohydride The sodium concentration is 25 to 75 mmol/L.

Preferably, the polarized barium titanate nanoparticles in step (3) are added to the bismuth nitrate pentahydrate solution, and ultrasonically dispersed for 10-30 minutes.

Preferably, the temperature of the reaction in step (3) is normal temperature (15-30° C.), and the time is 3-15 min.

Preferably, the centrifugal washing in step (3) refers to alternating centrifugal washing with absolute ethanol and deionized water for 3 to 5 times, wherein the centrifugal speed is 7000 to 9000 rpm, and the time is 5 to 10 min; Dry at 50～70℃.

Preferably, the bismuth/barium titanate heterojunction obtained in step (3) needs to be sterilized by ultraviolet light for 30-90 minutes before use.

A bismuth/barium titanate heterojunction capable of enhancing acoustic power and anti-tumor is prepared by the above preparation method.

The invention uses barium titanate piezoelectric nanoparticles and bismuth metal element to construct a heterojunction, and the built-in electric field generated under the ultrasonic response of barium titanate and the coupling of the bismuth heterojunction promote and regulate the carrier (electron-hole pair) Separation, increase the content of reactive oxygen species and enhance the efficacy of sonodynamic therapy. The raw material synthesized by the hydrothermal method and the one-step in-situ deposition method is green, non-toxic, convenient and economical, easy to prepare, enhances the killing force on tumors under the ultrasonic response, broadens the types of sonosensitizers in the sonodynamic therapy, and improves the It makes up for the defects and deficiencies of the low anti-tumor efficiency of the existing sonosensitizers.

The ratio of sodium borohydride to bismuth source in step 3 of the present invention seriously affects the generation effect of bismuth element. If the content of sodium borohydride is too high, the reduction reaction speed will be severe and difficult to control, which will easily lead to serious agglomeration of Bi element, or lead to direct self-nucleation and growth in solution to form Bi element and agglomerate, without forming Bi heterogeneity on the surface of barium titanate If the content of sodium borohydride is too low, it is easy to cause sodium borohydride to directly reduce the bismuth source in the solution, that is, to directly generate Bi in the solution, resulting in very little Bi heterojunction formed on the surface of barium titanate, so only Appropriate ratio of sodium borohydride to bismuth source can form bismuth/barium titanate heterojunction with uniform structure. In addition, the reaction time also has a certain influence on the formation of the bismuth/barium titanate heterojunction. The short reaction time can easily lead to the direct nucleation and growth of Bi in the solution, and the sodium borohydride cannot fully contact the surface of the barium titanate. If the length is too long, the simple element Bi is easily oxidized to bismuth oxide, which leads to the failure of the synthesis, or leads to serious aggregation of the elemental Bi, and self-nucleation and growth in the solution to form the elemental Bi without barium titanate forming a heterojunction.

Compared with the prior art, the present invention has the following advantages and beneficial effects:

(1) At present, the preparation method of barium titanate is mainly a high temperature sintering method. The present invention utilizes a simple hydrothermal reaction method to prepare tetragonal barium titanate nanoparticles, and the nanometer size is uniform, about 100-150 nm.

(2) In the present invention, the barium titanate nanoparticles are polarized to enhance their piezoelectricity, and the output value of the potential signal is about 0.04V under ultrasonic conditions.

(3) The present invention realizes for the first time that a bismuth heterojunction is loaded on the surface of the barium titanate piezoelectric material, and a P-N heterojunction is constructed, in which the bismuth element is uniformly distributed on the surface of the barium titanate piezoelectric nanoparticles, with uniform size and small particle size. About 5 to 10 nm.

(4) The construction of the bismuth/barium titanate heterojunction of the present invention enhances the separation of electron-hole pairs under the action of ultrasound, further promotes the generation of reactive oxygen species, thereby enhancing the effect of sonodynamic anti-tumor, and the enhancement efficiency reaches 27%, which is The construction of ultrasound-responsive nanoparticles for sonodynamic therapy provides a new idea.

(6) The bismuth/barium titanate provided by the present invention can not only be used for sonodynamic therapy, but the construction of bismuth heterojunction can also enhance the light absorption capacity of the material. Through subsequent reasonable design, the material can be used in photodynamic therapy, photothermal therapy, etc. It also has application potential in therapy and acousto-optic combination therapy.

Description of drawings

Figure 1 is a schematic diagram of a self-made polarization mold.

FIG. 2 is a scanning electron microscope (SEM) image of the BTO piezoelectric nanoparticles obtained in Example 1. FIG.

FIG. 3 is an X-ray diffraction (XRD) pattern of the BTO piezoelectric nanoparticles obtained in Example 1. FIG.

FIG. 4 is a graph of the electromechanical response of the BTO piezoelectric nanoparticles obtained in Example 1 under ultrasonic conditions (40 kHz, 0.3 W cm ⁻² ).

FIG. 5 is a scanning electron microscope (SEM) image of the Bi-BTO-1 piezoelectric nanoparticles obtained in Example 2. FIG.

FIG. 6 is an X-ray diffraction (XRD) pattern of the Bi-BTO-1 piezoelectric nanoparticles obtained in Example 2. FIG.

FIG. 7 is a scanning electron microscope (SEM) image of the Bi-BTO-2 piezoelectric nanoparticles obtained in Example 3. FIG.

FIG. 8 is a scanning electron microscope (SEM) image of the Bi-BTO-3 piezoelectric nanoparticles obtained in Example 4. FIG.

9 is a scanning electron microscope (SEM) image of Bi-BTO-4 piezoelectric nanoparticles in Comparative Example 1. FIG.

FIG. 10 is a scanning electron microscope (SEM) image of Bi-BTO-5 piezoelectric nanoparticles obtained in Comparative Example 2. FIG.

11 is the killing effect of Bi-BTO-1 piezoelectric nanoparticles combined with ultrasound in Example 5 on human breast cancer (MDA-MB-231).

12 is the biocompatibility characterization of Bi-BTO-1 piezoelectric nanoparticles in Example 6 on fibroblasts (L929).

Detailed ways

The present invention will be described in further detail below with reference to the embodiments and accompanying drawings, but the embodiments of the present invention are not limited thereto.

If the specific conditions are not indicated in the examples of the present invention, the conventional conditions or the conditions suggested by the manufacturer are used. The raw materials, reagents, etc., which are not specified by the manufacturer, are all conventional products that can be purchased from the market.

Example 1

1. Preparation of barium titanate piezoelectric nanoparticles:

(1) 25 mmol of tetrabutyl titanate was weighed and dissolved in 20 mL of absolute ethanol, then 5 mL of ammonia water was slowly added dropwise to the above solution at a rate of 0.5 mL/min, and stirred for 15 min to obtain A solution.

(2) weighing 35mmol of barium hydroxide octahydrate and dissolved in 50mL polytetrafluoroethylene lining containing 25mL of deionized water, heating while stirring under a 90°C water bath, until the barium hydroxide octahydrate is completely dissolved, to obtain B liquid.

(3) Slowly pour liquid A in (1) into liquid (2) B, and stir for 15 min. Then, 5 mL of ethanolamine was added dropwise at a rate of 0.5 mL/min, followed by stirring for 15 min.

(4) The polytetrafluoroethylene lining was put into a high temperature and high pressure reaction kettle, and the reaction was carried out at 200° C. for 48 hours. After the reaction was completed, the materials were alternately centrifuged and washed 3 times with absolute ethanol and deionized water, wherein the centrifugal speed was 8000 rpm for 5 min, and then dried in an oven at 60° C. for later use.

2. Polarization treatment:

The synthesized barium titanate nanoparticles were placed in a self-made polarization mold for high temperature and high pressure polarization treatment. The polarization parameters were set as: polarization temperature 100 °C, polarization electric field intensity 3 KV/cm, and polarization time 10 min. Denote the polarized barium titanate nanoparticles as BTO.

Figure 1 is a schematic diagram of a self-made polarization mold.

The SEM of the BTO is shown in FIG. 2 . The polarized barium titanate nanoparticles in this example have a cubic shape, and the particle size is small, ranging from 100 to 150 nm.

The XRD of BTO is shown in FIG. 3 , and the polarized barium titanate nanoparticles in this embodiment have a perovskite structure.

The electromechanical response of BTO under ultrasonic conditions (40kHz, 0.3W cm ^-2 ) is shown in Figure 4. The polarized barium titanate nanoparticles in this example generate a built-in electric field under ultrasonic conditions, and the potential is about 0.04V.

Example 2

Construction of Bismuth/Barium Titanate Heterojunction Piezoelectric Nanoparticles:

(1) Dissolve 0.2 mmol of bismuth nitrate pentahydrate in 40 mL of deionized water, and stir for 15 min.

(2) 0.3 g of the barium titanate nanoparticles synthesized by the hydrothermal method in Example 1 were weighed and added to the solution of (1), and ultrasonically dispersed for 15 minutes until the barium titanate nanoparticles were uniformly dispersed.

(3) 1 mmol of sodium borohydride was added to the solution of (2), and the reaction was stirred at room temperature for 10 min.

(4) Immediately after the completion of the reaction, the material was centrifuged alternately for 3 times with absolute ethanol and deionized water, wherein the centrifugal speed was 8000 rpm, and the time was 8 minutes, then dried at 60°C in an oven, and sterilized by ultraviolet light for 60 minutes. ,stand-by. The bismuth-supported barium titanate heterojunction is designated as Bi-BTO-1.

The SEM of Bi-BTO-1 is shown in Figure 5. Bi-BTO-1 prepared in this example is successfully loaded on the surface of barium titanate nanoparticles with bismuth metal element, and the loading is uniform, and the particle size of bismuth is between 5 and 10 nm. .

The XRD of Bi-BTO-1 is shown in FIG. 6 . In the diffraction pattern of Bi-BTO-1 prepared in this example, the diffraction peak of bismuth was successfully observed, indicating that bismuth was successfully loaded on the surface of barium titanate nanoparticles.

Example 3

(2) Weigh 0.3 g of the barium titanate nanoparticles synthesized by the hydrothermal method in Example 1 and add it to the solution (1), and ultrasonically disperse for 15 min until the barium titanate nanoparticles are uniformly dispersed.

(3) Add 2 mmol of sodium borohydride to the solution of (2), and stir the reaction at room temperature for 10 min.

(4) Immediately after the completion of the reaction, the material was centrifuged alternately for 3 times with absolute ethanol and deionized water, wherein the centrifugal speed was 8000 rpm, and the time was 8 minutes, then dried at 60°C in an oven, and sterilized by ultraviolet light for 60 minutes. ,stand-by. The bismuth-supported barium titanate heterojunction is designated as Bi-BTO-2.

The SEM of Bi-BTO-2 is shown in Figure 7. Bi-BTO-2 prepared in this example is successfully loaded on the surface of barium titanate nanoparticles with bismuth metal element, and the loading is uniform, and the particle size of bismuth is between 5 and 10 nm. .

Example 4

(3) Add 3 mmol of sodium borohydride to the solution of (2), and stir the reaction at room temperature for 10 min.

(4) Immediately after the completion of the reaction, the material was centrifuged alternately for 3 times with absolute ethanol and deionized water, wherein the centrifugal speed was 8000 rpm, and the time was 8 minutes, then dried at 60°C in an oven, and sterilized by ultraviolet light for 60 minutes. ,stand-by. The bismuth-supported barium titanate heterojunction is designated as Bi-BTO-3.

The SEM of Bi-BTO-3 is shown in Figure 8. The Bi-BTO-3 prepared in this example is successfully loaded on the surface of barium titanate nanoparticles with bismuth metal element, and the loading is uniform, and the particle size of bismuth is between 5 and 10 nm. .

Comparative Example 1

(2) 0.3 g of the barium titanate nanoparticles synthesized by the hydrothermal method in Example 1 were weighed and added to the solution (1), and stirred for 15 min until the barium titanate nanoparticles were uniformly dispersed.

(3) 0.4 mmol of sodium borohydride was added to the solution of (2), and the reaction was stirred for 10 min.

(4) Immediately after the completion of the reaction, the material was centrifuged alternately for 3 times with absolute ethanol and deionized water, wherein the centrifugal speed was 8000 rpm, and the time was 8 minutes, then dried at 60°C in an oven, and sterilized by ultraviolet light for 60 minutes. ,stand-by. The bismuth-supported barium titanate heterojunction is designated as Bi-BTO-4.

The SEM of Bi-BTO-4 is shown in FIG. 9 , in the Bi-BTO-4 prepared in this comparative example, the bismuth metal element is loaded on the surface of the barium titanate nanoparticles in a small amount and unevenly.

Comparative Example 2

(3) 4 mmol of sodium borohydride was added to the solution of (2), and the reaction was stirred for 10 min.

(4) Immediately after the completion of the reaction, the material was centrifuged alternately for 3 times with absolute ethanol and deionized water, wherein the centrifugal speed was 8000 rpm, and the time was 8 minutes, then dried at 60°C in an oven, and sterilized by ultraviolet light for 60 minutes. ,stand-by. The bismuth-supported barium titanate heterojunction is designated as Bi-BTO-5.

The SEM of Bi-BTO-5 is shown in Fig. 10. In the Bi-BTO-5 prepared in this comparative example, the bismuth metal element is loaded on the surface of the barium titanate nanoparticles in a small amount and unevenly.

Example 5

Human breast cancer cells (MDA-MB-231) were selected to test the anti-tumor effect of Bi-BTO-1 heterojunction piezoelectric nanoparticles under ultrasound (US). MDA-MB-231 cells were seeded in DMEM high-glucose medium containing 10% fetal bovine serum and 1% penicillin-streptomycin double antibody, and cultured in an incubator at 37°C, 5% carbon dioxide and saturated humidity. Growth phase cells.

MDA-MB-231 cancer cells in logarithmic growth phase were taken, the supernatant was discarded after centrifugation, and 3 mL of medium was taken to suspend the cells gently. The experimental group was divided into six groups: Control group, BTO group, Bi-BTO-1 group, US group, US+BTO group, US+Bi-BTO-1 group. MDA-MB-231 cancer cells with a cell density of 10 ⁴ cells/well were seeded in a 96-well plate, and 100 μL of DMEM high-glucose medium containing 10% fetal bovine serum and 1% penicillin-streptomycin double antibody was added to each well. There are six parallel samples in each group, and after culturing in a constant temperature incubator for 12 hours, after aspirating and discarding the medium, 100 μL of medium was added to the Control group and the US group, and 200 μg/mL of BTO diluted in the medium was added to the BTO group and the US+BTO group. 100 μL of solution, Bi-BTO-1 group and US+Bi-BTO-1 group were added with 100 μL of 200 μg/mL Bi-BTO-1 solution diluted in culture medium, and after co-cultivation for 12 h, ultrasonication (40 kHz, 0.3 W cm ^{− 2} ) After treatment for 60s and 4h, ultrasonic (40kHz, 0.3W cm ^-2 ) treatment was performed once, for a total of two treatments. After the treatment was completed, the cells were cultured in a constant temperature incubator for 12 h. When the co-cultivation time is up, aspirate the old medium, add the diluted CCK-8 working solution, incubate in a CO ₂ constant temperature incubator for 2 h, transfer to a new 96-well plate after the reaction, and then use a multi-function microplate reader Detect the absorbance of the reaction solution in the well plate at a wavelength of 450 nm. The relative viability of tumor cells was calculated using formula (1).

The results of this example are shown in Figure 11. The cell survival rates in the Control group, the BTO group and the Bi-BTO-1 group were similar, indicating that the material had no effect on the cell viability, and the US group MDA-MB-231 cancer cell survival rate was 81% , slightly decreased. Compared with other groups, the cell viability in the US+BTO group and the US+Bi-BTO-1 group was greatly reduced, and the cell viability was 57% and 30%, respectively. The survival rate was the lowest. Compared with the US+BTO group, the tumor cell killing rate increased by 27%, indicating that the Bi heterojunction can enhance the production of reactive oxygen species, enhance the sonodynamic efficacy, and have a more obvious lethality to cancer cells.

Example 6

Fibroblasts (L929) were selected to verify the biocompatibility of Bi-BTO-1. L929 cells were inoculated in DMEM high-glucose medium containing 10% fetal bovine serum and 1% penicillin-streptomycin double antibody, and cultured in an incubator at 37°C, 5% carbon dioxide and saturated humidity. The experiments were used for logarithmic growth phase cells .

L929 cells in logarithmic growth phase were taken, the supernatant was discarded after centrifugation, and 3 mL of medium was taken to suspend the cells gently. The experimental group was divided into three groups: Control group, BTO group and Bi-BTO-1 group. The L929 cells with a cell density of 5000 cells/well were seeded in a 96-well plate, and 100 μL of DMEM high-glucose medium containing 10% fetal bovine serum and 1% penicillin double antibody was added to each well, and six parallel samples in each group were added. , and then after culturing in a constant temperature incubator for 12 hours, after aspirating and discarding the medium, Control added 100 μL of medium, the BTO group added 100 μL of 200 μg/mL BTO solution diluted in the medium, and the Bi-BTO-1 group added 200 μg of the medium diluted /mL Bi-BTO-1 solution 100 μL, after co-cultivation for 12, 24, and 48 h, respectively, when the co-cultivation time is up, aspirate the old medium, add the diluted CCK-8 working solution, and incubate in a CO ₂ constant temperature incubator Incubate for 2 h, transfer to a new 96-well plate after the reaction, and then use a multi-function microplate reader to detect the absorbance of the reaction solution in the well plate at a wavelength of 450 nm.

The results of this example are shown in Figure 12. Compared with the Control group, the activity of L929 cells in the BTO group and the Bi-BTO-1 group has no obvious downward trend, which indicates that the two materials are non-toxic and have good biological properties. Capacitance.

The above-mentioned embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above-mentioned embodiments, and any other changes, modifications, substitutions, combinations, The simplification should be equivalent replacement manners, which are all included in the protection scope of the present invention.

Claims

A method for preparing a bismuth/barium titanate heterojunction that enhances sonodynamic anti-tumor features, comprising the following steps:

(1) drip ammonia water into the tetrabutyl titanate solution, add it to the octahydrate barium hydroxide solution after mixing, add ethanolamine dropwise after mixing, then hydrothermally react, centrifugally wash, and dry to obtain a nanometer barium titanate particles;

(2) performing high temperature and high pressure polarization treatment on the barium titanate nanoparticles to obtain polarized barium titanate nanoparticles;

(3) adding polarized barium titanate nanoparticles into the bismuth nitrate pentahydrate solution, after mixing uniformly, adding sodium borohydride for reaction, centrifugal washing, and drying to obtain a bismuth/barium titanate heterojunction.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustodynamic anti-tumor according to claim 1, wherein the concentration of the bismuth nitrate pentahydrate solution in step (3) is 2.5-7.5 mmol/L , the solvent is deionized water.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustodynamic anti-tumor according to claim 1, characterized in that, the temperature of the reaction in step (3) is normal temperature, and the time is 3-15 min.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustic dynamics and anti-tumor according to claim 1, characterized in that in step (3), the bismuth nitrate pentahydrate, polarized barium titanate nanoparticles and The molar ratio of sodium borohydride is 1:5.7:5～1:8.6:15.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustodynamic anti-tumor according to claim 1, wherein the parameter of the high temperature and high pressure polarization treatment in step (2) is: the polarization temperature is 90 ℃ ～110℃, the polarization electric field strength is 2～4KV/cm, and the polarization time is 5～15min.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustic dynamics and anti-tumor according to claim 1, wherein in step (1), tetrabutyl titanate, ammonia water, sodium hydroxide octahydrate and ethanolamine The molar ratio is 1:2.8:1.3:2.1～1:3.8:1.5:2.8.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustodynamic anti-tumor according to claim 1, wherein the concentration of the tetrabutyl titanate solution in step (1) is 0.8-2 mol/L , the solvent is absolute ethanol; the concentration of the octahydrate barium hydroxide solution is 1-2 mol/L, and the solvent is deionized water.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustodynamic anti-tumor according to claim 1, wherein the temperature of the hydrothermal reaction in step (1) is 180-210°C, and the time is 42 ～54h; the speed of the dropwise addition is all; under stirring state, the ammonia solution of tetrabutyl titanate in step (1) is poured into the barium hydroxide octahydrate solution, and then stirred for 10～30min.
The method for preparing a bismuth/barium titanate heterojunction for enhancing acoustodynamic anti-tumor according to claim 1, wherein the dropping rate of the ammonia water in step (1) is 0.5-1 mL/min; the ethanolamine The speed of the dropwise addition is 0.5 to 1 mL/min, and each is stirred for 10 to 30 minutes after the dropwise addition; the centrifugal washing in steps (1) and (3) refers to alternate centrifugal washing with absolute ethanol and deionized water for 3 to 5 times, wherein The centrifugal speed is 7000-9000 rpm, and the time is 5-10 minutes; the drying refers to drying at 50-70° C.; the polarized barium titanate nanoparticles in step (3) are added to the bismuth nitrate pentahydrate solution , ultrasonic dispersion 10 ~ 30min.
A bismuth/barium titanate heterojunction with enhanced sonodynamic anti-tumor prepared by the method of any one of claims 1 to 9.