CN113209290A - Bismuth/barium titanate heterojunction for enhancing acoustic power and resisting tumors and preparation method thereof - Google Patents
Bismuth/barium titanate heterojunction for enhancing acoustic power and resisting tumors and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an anti-tumor bismuth/barium titanate heterojunction capable of enhancing acoustic power and a preparation method thereof. The method comprises (1) preparing barium titanate nanoparticles by a hydrothermal method; (2) carrying out high-temperature high-pressure polarization treatment on the barium titanate nanoparticles; (3) and depositing a bismuth simple substance on the surface of the barium titanate nano particles by using a one-step in-situ deposition method to construct a bismuth/barium titanate P-N heterojunction. The bismuth/barium titanate heterojunction has good biocompatibility, high safety and good stability, and can enhance the acoustic dynamic anti-tumor effect.
Description
Technical Field
The invention belongs to the technical field of sonodynamic tumor treatment nano materials, and particularly relates to an anti-tumor bismuth/barium titanate heterojunction capable of enhancing sonodynamic and a preparation method thereof.
Background
Breast cancer is a serious threat to the health of humans, especially women. The current clinical treatment means for breast cancer mainly comprises surgical excision, chemotherapy, radiotherapy and the like. Surgical removal of the breast is often the first mode of treatment for breast cancer, but incomplete removal can lead to metastasis of cancer cells and recurrence of the cancer. Chemotherapy and radiotherapy are often used as auxiliary means to remove the microscopic lesions, but the side effects obviously cause the immune damage of patients or poor treatment effect. The therapy uses ultrasonic to activate the sound-sensitive agent to generate Reactive Oxygen Species (ROS) to kill cancer cells, can only target cancer cells without damaging surrounding normal cells or organs, and can also avoid side effects caused by the traditional tumor treatment means. In addition, the penetration depth of the ultrasonic wave in human tissues can reach 10cm, and the ultrasonic wave can be used for treating deep tumors.
Barium titanate has piezoelectricity, and can promote separation of electron-hole pairs and enhance generation of active oxygen due to a built-in electric field constructed under ultrasound, so that barium titanate is mainly applied to the field of catalysis at present. In addition, it has been shown that noble metal deposition can further enhance the electron hole pair separation and increase the yield of active oxygen. The bismuth metal is reported to have good biocompatibility, and compared with noble metals such as platinum and gold, the bismuth metal has the advantages of low price, rich resources, environmental friendliness, good optical and electrical conductivity and the like, and can replace the noble metals such as platinum and gold. At present, the nano-scale bismuth simple substance is mainly obtained by an electrochemical deposition method, and bismuth is plated on a three-dimensional cathode material by electroplating, but the method is only suitable for the three-dimensional material and is ineffective for loading the bismuth simple substance on the surface of the nano-material.
Disclosure of Invention
In order to overcome the defects and shortcomings in the prior art, the invention aims to provide a preparation method of an enhanced acoustic dynamic anti-tumor bismuth/barium titanate heterojunction.
Firstly, synthesizing barium titanate piezoelectric nanoparticles through hydrothermal treatment, then carrying out polarization treatment on the barium titanate nanoparticles through high-temperature high-pressure polarization, and then loading a bismuth simple substance on the surfaces of the barium titanate piezoelectric nanoparticles by utilizing a one-step in-situ deposition method to form a bismuth/barium titanate heterojunction.
The invention also aims to provide the bismuth/barium titanate heterojunction which is used for enhancing the acoustic dynamic force and resisting the tumor and is prepared by the method.
The bismuth/barium titanate heterojunction obtained by the invention can generate active oxygen with low tumor cell tolerance by combining non-invasive ultrasound to enhance the treatment effect of sonodynamic.
The purpose of the invention is realized by the following technical scheme:
a preparation method of an enhanced acoustic dynamic anti-tumor bismuth/barium titanate heterojunction comprises the following steps:
(1) dropwise adding ammonia water into tetrabutyl titanate solution, uniformly mixing, adding into barium hydroxide octahydrate solution, uniformly mixing, dropwise adding ethanolamine, performing hydrothermal reaction, centrifugally washing, and drying to obtain barium titanate nanoparticles;
(2) carrying out high-temperature high-pressure polarization treatment on the barium titanate nanoparticles to obtain polarized barium titanate nanoparticles;
(3) and adding the polarized barium titanate nano particles into a bismuth nitrate pentahydrate solution, uniformly mixing, adding sodium borohydride for reaction, centrifugally washing, and drying to obtain the bismuth/barium titanate heterojunction.
Preferably, the concentration of the tetrabutyl titanate solution in the step (1) is 0.8-2 mol/L, the solvent is absolute ethyl alcohol, and the tetrabutyl titanate solution is dissolved at normal temperature; the concentration of the barium hydroxide octahydrate solution is 1-2 mol/L, the solvent is deionized water, and the dissolving temperature is 80-100 ℃.
Preferably, the molar ratio of tetrabutyl titanate, ammonia water, sodium hydroxide octahydrate and ethanolamine in step (1) is 1:2.8:1.3: 2-1: 3.8:1.5: 2.8.
Preferably, the dropping speed of the ammonia water in the step (1) is 0.5-1 mL/min; the dropping speed of the ethanolamine is 0.5-1 mL/min.
Preferably, the ammonia water and the ethanolamine are respectively added dropwise in the step (1) and then stirred for 10-30 min.
Preferably, the temperature of the hydrothermal reaction in the step (1) is 180-210 ℃, and the time is 42-54 h.
Preferably, the centrifugal washing in the step (1) refers to alternately and centrifugally washing for 3-5 times by using absolute ethyl alcohol and deionized water, wherein the centrifugal rotating speed is 7000-9000 r/min, and the time is 5-10 min; the drying refers to drying at 50-70 ℃.
Preferably, the parameters of the high-temperature high-pressure polarization treatment in the step (2) are as follows: the polarization temperature is 90-110 ℃, the polarization electric field intensity is 2-4 KV/cm, and the polarization time is 5-15 min.
Preferably, the molar ratio of bismuth nitrate pentahydrate, polarized barium titanate nanoparticles and sodium borohydride in step (3) is 1: 5.7: 5-1: 8.6: 15.
preferably, the solvent of the bismuth nitrate pentahydrate solution in the step (3) is deionized water, wherein the concentration of the polarized barium titanate nanoparticles is 5-10 mg/mL, the concentration of the bismuth nitrate pentahydrate is 2.5-7.5 mmol/L, and the concentration of the sodium borohydride is 25-75 mmol/L.
Preferably, the polarized barium titanate nanoparticles obtained in the step (3) are added into a bismuth nitrate pentahydrate solution, and are subjected to ultrasonic dispersion for 10-30 min.
Preferably, the reaction in the step (3) is carried out at normal temperature (15-30 ℃) for 3-15 min.
Preferably, the centrifugal washing in the step (3) is alternately centrifugal washing with absolute ethyl alcohol and deionized water for 3-5 times, wherein the centrifugal rotating speed is 7000-9000 r/min, and the time is 5-10 min; the drying is drying at 50-70 ℃.
Preferably, the bismuth/barium titanate heterojunction obtained in the step (3) can be used after being subjected to ultraviolet sterilization for 30-90 min.
An anti-tumor bismuth/barium titanate heterojunction with enhanced acoustic power is prepared by the preparation method.
According to the invention, the barium titanate piezoelectric nanoparticles and the bismuth metal simple substance are utilized to construct a heterojunction, and the separation of carriers (electron hole pairs) is promoted and regulated through the coupling of a built-in electric field generated under the ultrasonic response of barium titanate and the bismuth heterojunction, so that the generation content of active oxygen is improved, and the curative effect of the acoustic dynamic therapy is enhanced. The raw materials synthesized by the hydrothermal method and the one-step in-situ deposition method adopted by the invention are green, nontoxic, convenient, economical and easy to prepare, the killing acting force on the tumor is enhanced under ultrasonic response, the variety of the acoustic sensitizer in the acoustic dynamic therapy is widened, and the defect of low anti-tumor efficiency of the existing acoustic sensitizer are overcome.
The ratio of sodium borohydride to bismuth source in step 3 of the invention seriously affects the generation effect of the bismuth simple substance. If the content of sodium borohydride is too high, the reduction reaction speed is severe and difficult to control, which easily causes serious aggregation of the elementary substance Bi, or leads to the direct self-nucleation growth in the solution to form the elementary substance Bi and to aggregate, but does not form a Bi heterojunction on the surface of barium titanate; if the content of the sodium borohydride is too low, the sodium borohydride is easy to directly reduce the bismuth source in the solution, namely, a Bi simple substance is directly generated in the solution, so that the content of a Bi heterojunction formed on the surface of the barium titanate is very low, and the bismuth/barium titanate heterojunction with a uniform structure can be formed only by a proper ratio of the sodium borohydride to the bismuth source. In addition, the reaction time has certain influence on the formation of bismuth/barium titanate heterojunction, the reaction time is short, the direct nucleation growth of the Bi simple substance in the solution is easily caused, and the sodium borohydride can not be fully contacted with the surface of the barium titanate; the reaction time is too long, the Bi simple substance is easily oxidized into bismuth oxide, so that the synthesis fails, or the Bi simple substance is seriously aggregated, and the Bi simple substance is formed by self-nucleation growth in the solution without forming a heterojunction by barium titanate.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) at present, the preparation method of barium titanate is mainly a high-temperature sintering method, and the invention prepares tetragonal-phase barium titanate nanoparticles with uniform nanometer size of about 100-150 nm by using a simple hydrothermal reaction method.
(2) The invention polarizes the barium titanate nano-particles to enhance the piezoelectricity thereof, and the potential signal output value of the barium titanate nano-particles under the ultrasonic condition is about 0.04V.
(3) According to the invention, the bismuth heterojunction is loaded on the surface of the barium titanate piezoelectric material for the first time, and the P-N heterojunction is constructed, wherein the bismuth simple substance is uniformly distributed on the surface of the barium titanate piezoelectric nano-particles, and the barium titanate piezoelectric nano-particles have uniform size and small particle size of about 5-10 nm.
(4) The construction of the bismuth/barium titanate heterojunction enhances the separation of electron hole pairs under the action of ultrasound, further promotes the generation of active oxygen, thereby enhancing the anti-tumor effect of acoustic power, enhancing the efficiency by 27 percent and providing a new idea for constructing nanoparticles with ultrasonic response to be applied to the treatment of the acoustic power therapy.
(6) The bismuth/barium titanate provided by the invention can be used for the acoustodynamic therapy, the bismuth heterojunction can enhance the light absorption capacity of the material, and the material has application potential in the photodynamic therapy, the photothermal therapy and the acousto-optic combination therapy through reasonable design.
Drawings
FIG. 1 is a schematic view 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. 3 is an X-ray diffraction (XRD) pattern of the BTO piezoelectric nanoparticles obtained in example 1.
FIG. 4 shows BTO piezoelectric nanoparticles obtained in example 1 under ultrasonic conditions (40kHz, 0.3W cm)-2) Force electrical response diagram below.
FIG. 5 is a Scanning Electron Microscope (SEM) image of the Bi-BTO-1 piezoelectric nanoparticles obtained in example 2.
FIG. 6 is an X-ray diffraction (XRD) pattern of Bi-BTO-1 piezoelectric nanoparticles obtained in example 2.
FIG. 7 is a Scanning Electron Microscope (SEM) image of the Bi-BTO-2 piezoelectric nanoparticles obtained in example 3.
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 the Bi-BTO-4 piezoelectric nanoparticles of comparative example 1.
FIG. 10 is a Scanning Electron Microscope (SEM) image of the Bi-BTO-5 piezoelectric nanoparticles obtained in comparative example 2.
FIG. 11 is the effect of Bi-BTO-1 piezoelectric nanoparticles in combination with ultrasound on the killing of human-derived breast cancer (MDA-MB-231) in example 5.
FIG. 12 shows the biocompatibility characterization of the Bi-BTO-1 piezoelectric nanoparticles to fibroblasts (L929) in example 6.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto.
Those who do not specify specific conditions in the examples of the present invention follow conventional conditions or conditions recommended by the manufacturer. The raw materials, reagents and the like which are not indicated for manufacturers are all conventional products which can be obtained by commercial purchase.
Example 1
1. Preparing barium titanate piezoelectric nanoparticles:
(1) after 25mmol of tetrabutyl titanate was weighed and dissolved in 20mL of absolute ethanol, 5mL of aqueous ammonia was slowly dropped into the solution at a dropping rate of 0.5mL/min, and the solution was stirred for 15min to obtain solution A.
(2) 35mmol of barium hydroxide octahydrate was weighed and dissolved in a 50mL polytetrafluoroethylene liner containing 25mL of deionized water, and the mixture was heated with stirring in a water bath at 90 ℃ until the barium hydroxide octahydrate was completely dissolved, to obtain solution B.
(3) Slowly pouring the solution A in the step (1) into the solution B in the step (2), and stirring for 15 min. Then, 5mL of ethanolamine was added dropwise at a rate of 0.5mL/min, followed by stirring for 15 min.
(4) And (3) putting the polytetrafluoroethylene lining into a high-temperature high-pressure reaction kettle, and reacting for 48 hours at 200 ℃. After the reaction is finished, the material is respectively and alternately washed by centrifugation for 3 times by using absolute ethyl alcohol and deionized water, wherein the centrifugation speed is 8000 revolutions per minute, and the time is 5 minutes, and then the material is dried in an oven at 60 ℃ for standby.
2. And (3) polarization treatment:
and (2) loading the synthesized barium titanate nanoparticles into a self-made polarization mold for high-temperature and high-pressure polarization treatment, wherein the polarization parameters are set as follows: the polarization temperature is 100 ℃, the polarization electric field intensity is 3KV/cm, and the polarization time is 10 min. The polarized barium titanate nanoparticles were noted as BTO.
FIG. 1 is a schematic view of a self-made polarization mold.
As shown in fig. 2, the SEM of BTO shows that the barium titanate nanoparticles after polarization in this example are cubic, and have a small particle size of 100 to 150 nm.
As shown in fig. 3, XRD of BTO shows that the barium titanate nanoparticles after polarization in this example have a perovskite structure.
Ultrasonic condition of BTO (40kHz, 0.3W cm)-2) The force-electricity response of the barium titanate nanoparticles polarized in this example is shown in fig. 4, and the electric potential of the barium titanate nanoparticles is about 0.04V.
Example 2
Construction of bismuth/barium titanate heterojunction piezoelectric nanoparticles:
(1) 0.2mmol of bismuth nitrate pentahydrate was weighed and dissolved in 40mL of deionized water, and stirred for 15 min.
(2) 0.3g of barium titanate nanoparticles synthesized by the hydrothermal method of example 1 was weighed and added to the solution of (1), and ultrasonically dispersed for 15min until the barium titanate nanoparticles were uniformly dispersed.
(3) 1mmol of sodium borohydride in the solution (2) is added, and the reaction is stirred at room temperature for 10 min.
(4) And respectively and alternately centrifuging and washing the material for 3 times by using absolute ethyl alcohol and deionized water immediately after the reaction is finished, wherein the centrifugation speed is 8000 revolutions per minute and the time is 8 minutes, and then drying in an oven at 60 ℃ and carrying out ultraviolet sterilization for 60 minutes for later use. The bismuth-loaded barium titanate heterojunction is recorded as Bi-BTO-1.
As shown in FIG. 5, in the SEM of Bi-BTO-1, in the Bi-BTO-1 prepared in the present embodiment, the bismuth metal simple substance is successfully loaded on the surface of the barium titanate nanoparticles, and the loading is uniform, and the particle size of bismuth is between 5 nm and 10 nm.
XRD of Bi-BTO-1 As shown in FIG. 6, diffraction peaks of bismuth were successfully observed in the diffraction pattern of Bi-BTO-1 prepared in this example, indicating that bismuth was successfully supported on the surface of barium titanate nanoparticles.
Example 3
Construction of bismuth/barium titanate heterojunction piezoelectric nanoparticles:
(1) 0.2mmol of bismuth nitrate pentahydrate was weighed and dissolved in 40mL of deionized water, and stirred for 15 min.
(2) 0.3g of barium titanate nanoparticles synthesized by the hydrothermal method of example 1 was weighed and added to the solution of (1), and ultrasonically dispersed for 15min until the barium titanate nanoparticles were uniformly dispersed.
(3) 2mmol of sodium borohydride in the solution (2) is added, and the reaction is stirred at room temperature for 10 min.
(4) And respectively and alternately centrifuging and washing the material for 3 times by using absolute ethyl alcohol and deionized water immediately after the reaction is finished, wherein the centrifugation speed is 8000 revolutions per minute and the time is 8 minutes, and then drying in an oven at 60 ℃ and carrying out ultraviolet sterilization for 60 minutes for later use. The bismuth-loaded barium titanate heterojunction is recorded as Bi-BTO-2.
As shown in FIG. 7, in the SEM of Bi-BTO-2, in the Bi-BTO-2 prepared in the present embodiment, the bismuth metal simple substance is successfully loaded on the surface of the barium titanate nanoparticles, and the loading is uniform, and the particle size of bismuth is between 5 nm and 10 nm.
Example 4
Construction of bismuth/barium titanate heterojunction piezoelectric nanoparticles:
(1) 0.2mmol of bismuth nitrate pentahydrate was weighed and dissolved in 40mL of deionized water, and stirred for 15 min.
(2) 0.3g of barium titanate nanoparticles synthesized by the hydrothermal method of example 1 was weighed and added to the solution of (1), and ultrasonically dispersed for 15min until the barium titanate nanoparticles were uniformly dispersed.
(3) And 3mmol of sodium borohydride in the solution (2) is added, and the reaction is stirred at room temperature for 10 min.
(4) And respectively and alternately centrifuging and washing the material for 3 times by using absolute ethyl alcohol and deionized water immediately after the reaction is finished, wherein the centrifugation speed is 8000 revolutions per minute and the time is 8 minutes, and then drying in an oven at 60 ℃ and carrying out ultraviolet sterilization for 60 minutes for later use. And recording the bismuth-loaded barium titanate heterojunction as Bi-BTO-3.
As shown in FIG. 8, in the SEM of Bi-BTO-3, in the Bi-BTO-3 prepared in the present embodiment, the bismuth metal simple substance is successfully loaded on the surface of the barium titanate nanoparticles, and the loading is uniform, and the particle size of bismuth is between 5 nm and 10 nm.
Comparative example 1
Construction of bismuth/barium titanate heterojunction piezoelectric nanoparticles:
(1) 0.2mmol of bismuth nitrate pentahydrate was weighed and dissolved in 40mL of deionized water, and stirred for 15 min.
(2) 0.3g of barium titanate nanoparticles synthesized by the hydrothermal method of example 1 was weighed and added to the solution of (1), and stirred for 15min until the barium titanate nanoparticles were uniformly dispersed.
(3) And adding 0.4mmol of sodium borohydride into the solution (2), and stirring for reaction for 10 min.
(4) And respectively and alternately centrifuging and washing the material for 3 times by using absolute ethyl alcohol and deionized water immediately after the reaction is finished, wherein the centrifugation speed is 8000 revolutions per minute and the time is 8 minutes, and then drying in an oven at 60 ℃ and carrying out ultraviolet sterilization for 60 minutes for later use. The bismuth-loaded barium titanate heterojunction is recorded as Bi-BTO-4.
SEM of Bi-BTO-4 As shown in FIG. 9, in the Bi-BTO-4 prepared in this comparative example, the simple substance of bismuth metal was slightly and unevenly supported on the surface of the barium titanate nanoparticles.
Comparative example 2
Construction of bismuth/barium titanate heterojunction piezoelectric nanoparticles:
(1) 0.2mmol of bismuth nitrate pentahydrate was weighed and dissolved in 40mL of deionized water, and stirred for 15 min.
(2) 0.3g of barium titanate nanoparticles synthesized by the hydrothermal method of example 1 was weighed and added to the solution of (1), and stirred for 15min until the barium titanate nanoparticles were uniformly dispersed.
(3) 4mmol of sodium borohydride in the solution (2) is added, and the reaction is stirred for 10 min.
(4) And respectively and alternately centrifuging and washing the material for 3 times by using absolute ethyl alcohol and deionized water immediately after the reaction is finished, wherein the centrifugation speed is 8000 revolutions per minute and the time is 8 minutes, and then drying in an oven at 60 ℃ and carrying out ultraviolet sterilization for 60 minutes for later use. The bismuth-loaded barium titanate heterojunction is recorded as Bi-BTO-5.
SEM of Bi-BTO-5 As shown in FIG. 10, in the Bi-BTO-5 prepared in the present comparative example, the bismuth metal simple substance was slightly and unevenly supported on the surface of the barium titanate nanoparticles.
Example 5
Human breast cancer cells (MDA-MB-231) are selected for testing the anti-tumor effect of the Bi-BTO-1 heterojunction piezoelectric nano-particles under the Ultrasonic (US) condition. MDA-MB-231 cells are inoculated in DMEM high-sugar medium containing 10% fetal calf serum and 1% streptomycin double antibody, and cultured in an incubator with 37 ℃, 5% carbon dioxide and saturated humidity, and cells in logarithmic growth phase are used in experiments.
MDA-MB-231 cancer cells in logarithmic growth phase are taken, centrifuged, supernatant is discarded, and 3mL of culture medium is taken to lightly blow and suspend the cells. The experimental components were divided into six groups: control group, BTO group, Bi-BTO-1 group, US + BTO groupGroup US + Bi-BTO-1. The cell density was 104MDA-MB-231 cancer cells are inoculated into a 96-well plate, 100 mu L of DMEM high-sugar medium containing 10% fetal bovine serum and 1% streptomycin double antibody is added into each well, each group of six parallel samples are cultured in a constant-temperature incubator for 12 hours, then after the medium is sucked and discarded, 100 mu L of the medium is added into a Control group and a US group, 100 mu L of BTO solution of 200 mu g/mL diluted by the medium is added into a BTO group and a US + BTO group, 100 mu L of Bi-BTO-1 solution of 200 mu g/mL diluted by the medium is added into a Bi-BTO-1 group and a Bi + BTO-1 group, and after the co-culture is continued for 12 hours, ultrasound (40kHz, 0.3W cm) is carried out-2) Treating for 60s, 4h, and then performing ultrasonic treatment (40kHz, 0.3W cm)-2) The treatment is carried out once and the treatment is carried out twice. After the treatment is completed, the culture is carried out in a constant temperature incubator for 12 hours. When the CO-culture time is up, the old culture medium is discarded, the diluted CCK-8 working solution is added, and CO is added2And (3) incubating for 2h in a constant-temperature incubator, transferring the reaction product into a new 96-well plate after reaction, and detecting the absorbance of the reaction solution in the well plate at the wavelength of 450nm by using a multifunctional microplate reader. The relative activity of tumor cells was calculated using formula (1).
The results of this example are shown in fig. 11, where the cell survival rates of the Control group, BTO group and Bi-BTO-1 group are similar, which indicates that the material has no influence on the cell activity, the survival rate of MDA-MB-231 cancer cell in the US group is 81%, which is slightly lower, and compared with other groups, the cell survival rates of US + BTO group and US + Bi-BTO-1 group are greatly reduced, which are 57% and 30%, respectively, wherein the survival rate of US + Bi-BTO-1 group is the lowest, and the tumor cell killing rate is increased by 27% compared with US + BTO group, which indicates that the Bi heterojunction can enhance the generation of active oxygen, enhance the acoustic dynamic curative effect, and has more obvious killing power on cancer cells.
Example 6
Fibroblast (L929) is selected to verify that the Bi-BTO-1 biocompatibility exists. L929 cells were inoculated in DMEM high-sugar medium containing 10% fetal calf serum and 1% streptomycin double antibody, cultured in an incubator containing 5% carbon dioxide and saturated humidity at 37 ℃, and used in the experiment as cells in the logarithmic growth phase.
Taking L929 cells in a logarithmic phase, centrifuging, removing supernatant, and taking 3mL of culture medium to lightly blow and suspend the cells. The experimental components are three groups: control group, BTO group, Bi-BTO-1 group. Inoculating L929 cells with the cell density of 5000 cells/well into a 96-well plate, adding 100 mu L of DMEM high-sugar medium containing 10% fetal calf serum and 1% streptomycin double antibody into each well, adding six parallel samples into each group, then culturing in a constant-temperature incubator for 12h, sucking and removing the medium, adding 100 mu L of the medium into Control, adding 100 mu L of BTO solution diluted by the medium into BTO group, adding 100 mu L of Bi-BTO-1 solution diluted by the medium into Bi-BTO-1 group, respectively CO-culturing for 12, 24 and 48h, waiting for CO-culturing time, sucking and removing the old medium, adding diluted CCK-8 working solution, and adding CO2And (3) incubating for 2h in a constant-temperature incubator, transferring the reaction product into a new 96-well plate after reaction, and detecting the absorbance of the reaction solution in the well plate at the wavelength of 450nm by using a multifunctional microplate reader.
The results of this example are shown in FIG. 12, and compared with the Control group, the activity of L929 cells in the BTO group and the Bi-BTO-1 group did not have a significant decrease tendency, thereby indicating that both materials are non-toxic and have good biocompatibility.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A preparation method of an enhanced acoustic power anti-tumor bismuth/barium titanate heterojunction is characterized by comprising the following steps:
(1) dropwise adding ammonia water into tetrabutyl titanate solution, uniformly mixing, adding into barium hydroxide octahydrate solution, uniformly mixing, dropwise adding ethanolamine, performing hydrothermal reaction, centrifugally washing, and drying to obtain barium titanate nanoparticles;
(2) carrying out high-temperature high-pressure polarization treatment on the barium titanate nanoparticles to obtain polarized barium titanate nanoparticles;
(3) and adding the polarized barium titanate nano particles into a bismuth nitrate pentahydrate solution, uniformly mixing, adding sodium borohydride for reaction, centrifugally washing, and drying to obtain the bismuth/barium titanate heterojunction.
2. The method for preparing the enhanced sonodynamic antitumor bismuth/barium titanate heterojunction as claimed in claim 1, wherein the concentration of the bismuth nitrate pentahydrate solution in the step (3) is 2.5-7.5 mmol/L, and the solvent is deionized water.
3. The method for preparing the bismuth/barium titanate heterojunction capable of enhancing the acoustic power and resisting the tumor according to claim 1, wherein the reaction temperature in the step (3) is normal temperature, and the reaction time is 3-15 min.
4. The method for preparing an enhanced sonodynamic antitumor bismuth/barium titanate heterojunction as claimed in claim 1, wherein the molar ratio of the bismuth nitrate pentahydrate, the polarized barium titanate nanoparticles and the sodium borohydride in step (3) is 1: 5.7: 5-1: 8.6: 15.
5. the method for preparing the bismuth/barium titanate heterojunction for enhancing the acoustodynamic force and resisting the tumor according to claim 1, wherein the parameters of the high-temperature high-pressure polarization treatment in the step (2) are as follows: the polarization temperature is 90-110 ℃, the polarization electric field intensity is 2-4 KV/cm, and the polarization time is 5-15 min.
6. The method for preparing the bismuth/barium titanate heterojunction for enhancing the sonodynamic force and resisting the tumor according to claim 1, wherein the molar ratio of tetrabutyl titanate, ammonia water, sodium hydroxide octahydrate and ethanolamine in the step (1) is 1:2.8:1.3: 2.1-1: 3.8:1.5: 2.8.
7. the method for preparing the bismuth/barium titanate heterojunction capable of enhancing the sonodynamic force and resisting the tumor according to claim 1, wherein the concentration of the tetrabutyl titanate solution in the step (1) is 0.8-2 mol/L, and the solvent is absolute ethyl alcohol; the concentration of the barium hydroxide octahydrate solution is 1-2 mol/L, and the solvent is deionized water.
8. The preparation method of the bismuth/barium titanate heterojunction for enhancing the acoustodynamic force and resisting the tumor according to claim 1, wherein the temperature of the hydrothermal reaction in the step (1) is 180-210 ℃, and the time is 42-54 h; the dropping speed is all the same; and (2) pouring the tetrabutyl titanate ammonia water solution in the step (1) into the barium hydroxide octahydrate solution under the stirring state, and then stirring for 10-30 min.
9. The preparation method of the bismuth/barium titanate heterojunction for enhancing the acoustodynamic force and resisting the tumor according to claim 1, wherein the dropping speed of the ammonia water in the step (1) is 0.5-1 mL/min; the dropping speed of the ethanolamine is 0.5-1 mL/min, and the ethanolamine is stirred for 10-30 min after dropping; the centrifugal washing in the steps (1) and (3) is alternately and centrifugally washed for 3-5 times by using absolute ethyl alcohol and deionized water, wherein the centrifugal rotating speed is 7000-9000 r/min, and the time is 5-10 min; the drying refers to drying at 50-70 ℃; and (3) adding the polarized barium titanate nanoparticles into a bismuth nitrate pentahydrate solution, and performing ultrasonic dispersion for 10-30 min.
10. An enhanced sonodynamic antitumor bismuth/barium titanate heterojunction prepared by the method of any one of claims 1 to 9.
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| WO2022217871A1 (en) * | 2021-04-12 | 2022-10-20 | 华南理工大学 | Bismuth/barium titanate heterojunction for enhancing sonodynamic antitumor effect and preparation method therefor |
| CN115944732A (en) * | 2023-03-14 | 2023-04-11 | 成都中医药大学 | Bismuth-based porous nano material and preparation method and application thereof |
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