Acoustic electric Ba triggering post-translational modification 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles, method of making and use thereof

Abstract

The application relates to the technical field of biology, and particularly relates to a sound electricity Ba that triggers post-translational modification 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles, a preparation method and application thereof. A titanium tetrachloride solution and a mixed reagent solution are stirred and mixed to obtain a stirring mixed solution; the stirring mixed solution is mixed with sodium hydroxide and polyvinylpyrrolidone and then subjected to heat treatment to obtain a heat-treated product; the heat-treated product is subjected to solid-liquid separation to obtain a solid, and the solid is washed to be neutral and dried. + The nanoparticles provided by the application consume H + around mitochondria under ultrasonic stimulation, leading to depolarization of a mitochondrial membrane potential. After the mitochondrial membrane potential is depolarized, E3 ubiquitin ligase Parkin is transferred from a cytoplasm to a mitochondrial outer membrane, and is massively aggregated and accumulated on the mitochondrial outer membrane, leading to ubiquitination modification and cascade degradation of an anti-apoptotic protein MCL-1 of the mitochondrial outer membrane, so that cell apoptosis is promoted.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biotechnology, in particular to a sound electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles, a preparation method and application thereof. BACKGROUND

[0002] Post-translational modification is an important regulatory mechanism that changes the properties of proteins by covalently attaching modified chemical groups to some amino acid residues. Post-translational modification regulates important physiological processes such as signal transduction, metabolism, protein localization and transformation, and has wide clinical significance in diseases such as cardiovascular disease, metabolic disorder and cancer. Post-translational modification is an important aspect of epigenetic regulation of life activities. They are usually catalyzed by enzymes and are the main regulators of protein activity, including various modifications such as ubiquitination, methylation, acetylation, glycosylation, etc. Among them, protein ubiquitination modification is a dynamic post-translational modification process based on molecular cascade, which is involved in almost all life processes of eukaryotes. Ubiquitination modification is a multi-step process mediated by three types of enzymes: ubiquitin activating enzyme (E1), ubiquitin coupling enzyme (E2) and ubiquitin ligase (E3). Ubiquitin is first activated by E1, then transferred to E2 binding enzyme. Subsequently, E3 ubiquitin ligase interacts with E2 loaded with ubiquitin and substrate protein, forming an isopeptide bond between the C-terminal of ubiquitin and the substrate lysine. This process regulates the stability, localization and function of proteins, and ultimately affects basic cellular processes such as cell cycle progression and DNA repair. Therefore, post-translational modification has a wide impact on cell fate regulation. They can cause activation or inhibition of pathways, assembly or degradation of protein complexes, and accumulation or relocation of proteins.

[0003] Currently, many small molecule compounds have been developed in the laboratory to achieve post-translational modification to regulate cell fate. In 2004, the first epigenetic drug approved by the US Food and Drug Administration (FDA) is azacitidine (Vidaza), which causes DNA demethylation by inhibiting the DNMT1 enzyme responsible for maintaining DNA methylation, for the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. HDAC inhibitors (HDACi) can regulate histone post-translational modification at the epigenetic level and regulate protein expression. HDACi can regulate metabolic pathway proteins by increasing histone acetylation, or reverse epithelial-mesenchymal transition by regulating ubiquitination pathways. The first HDAC inhibitor is suberoylanilide hydroxamic acid (SAHA, vorinostat), which was approved by the FDA in 2006 for the treatment of cutaneous manifestations of T-cell lymphoma (CTCL). Vorinostat can induce growth arrest, differentiation or apoptosis of various transformed cells. However, these drugs have side effects such as leukopenia, neutropenia and thrombocytopenia, and gastrointestinal symptoms such as nausea, vomiting, diarrhea and constipation. This can be due to the drug's target throughout the body, so the drug's off-target effects explain the emergence of adverse reactions. These cases have verified that it is possible to regulate the post-translational modification process of cells. However, the use of most post-translational modification regulatory enzyme inhibitors is limited by their poor bioavailability, cytotoxicity and specificity. Therefore, it is crucial to develop new strategies for post-translational modification regulation with specific targets and selectivity. SUMMARY

[0004] To solve the above problems, the present application provides a sound electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles and a preparation method and application thereof, reports a non-drug strategy based on sound electric nanomaterials for directly manipulating cell post-translational modification. This work provides the earliest example of non-drug nanoparticles directly manipulating post-translational modification changes. It realizes the precise positioning of drug sites and targets, makes up for the shortcomings of small molecule compounds, and reveals a new mechanism for nanoparticles to directly manipulate epigenetic modifications.

[0005] To achieve the above purpose, the present application provides the following technical solutions:

[0006] The present application provides a sound electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles and a preparation method and application thereof, reports a non-drug strategy based on sound electric nanomaterials for directly manipulating cell post-translational modification. This work provides the earliest example of non-drug nanoparticles directly manipulating post-translational modification changes. It realizes the precise positioning of drug sites and targets, makes up for the shortcomings of small molecule compounds, and reveals a new mechanism for nanoparticles to directly manipulate epigenetic modifications.

[0007] 1) Stir and mix the titanium tetrachloride solution and the mixed reagent solution to obtain a stirring mixed solution;

[0008] The concentration of the titanium tetrachloride solution is 0.9 mmol / ml;

[0009] The molar content of barium chloride in each 30 ml mixed reagent solution is 12.75 mmol, the molar content of calcium chloride is 2.25 mmol, and the molar content of ytterbium chloride is 1 mmol;

[0010] 2) The stirring mixed solution is mixed with sodium hydroxide and polyvinylpyrrolidone and then subjected to heat treatment to obtain a heat-treated product;

[0011] 3) The heat-treated product obtained in step 2) is subjected to solid-liquid separation to obtain a solid, which is washed to neutral and dried to obtain the piezoelectric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles.

[0012] Preferably, the volume ratio of the titanium tetrachloride solution to the mixed reagent solution in step 1) is 1:3.

[0013] Preferably, the stirring time of the mixed solution in step 1) is 30 min.

[0014] Preferably, the volume ratio of the stirring mixed solution to the mass of sodium hydroxide and the mass of polyvinylpyrrolidone in step 2) is 40 ml:3.6 g:1.2 g.

[0015] The molecular weight of the polyvinylpyrrolidone is 8000 Da.

[0016] Preferably, the mixing time in step 2) is 30 min.

[0017] Preferably, the heat treatment conditions in step 2) include a temperature of 200°C and a time of 20 h.

[0018] Preferably, deionized water and anhydrous ethanol are used for washing to neutral in step 3).

[0019] Preferably, the drying conditions in step 3) include a temperature of 80°C and a time of 12 h.

[0020] The present application provides the piezoelectric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles prepared by the preparation method of the above technical solution.

[0021] The present application also provides the piezoelectric Ba 0.85 Ca 0.15 Ti 0.9Yb 0.1 Use of O3 nanoparticles in preparation of drugs for promoting post-translational modification of tumor cells.

[0022] Advantages of the present application:

[0023] 1) Doping of Ca and Yb and changes in their electronic structure to improve the conductivity and covalent bond strength of BCT: Yb nanoparticles.

[0024] 2) The piezoelectric coefficient d33 reflects the piezoelectric performance of the nanoparticles. The d33 of BTO is only 320.67 pm / V, while the d33 of BCT: Yb is as high as 545.97 pm / V, indicating that the doping of Ca and Yb elements improves the piezoelectric performance, further confirming that the synthesized BCT: Yb has excellent piezoelectric performance.

[0025] 3) Under the stimulation of BCT: Yb piezoelectric nanomaterials, Parkin is transferred from the cytoplasm to the mitochondria by promoting the depolarization of the mitochondrial membrane potential, resulting in the recruitment and accumulation of Parkin on the mitochondria, thereby ubiquitinating and degrading the anti-apoptotic protein Mcl-1 on the outer membrane of the mitochondria, and achieving control of the growth of cancer cells. BRIEF DESCRIPTION OF DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiments will be briefly introduced below.

[0027] Figure 1 TEM of BCT: Yb nanoparticles;

[0028] Figure 2 High-magnification TEM of BCT: Yb nanoparticles;

[0029] Figure 3 Scanning electron microscope image of BCT: Yb nanoparticles;

[0030] Figure 4 TEM-mapping image of BCT: Yb (combined and individual elements: Ba, Ti, O, Ca, Yb);

[0031] Figure 5 X-ray diffraction pattern of BCT: Yb;

[0032] Figure 6 X-ray photoelectron spectrogram of BCT: Yb;

[0033] Figure 7 Infrared spectrogram of BCT: Yb;

[0034] Figure 8Raman spectrum of BCT: Yb;

[0035] Figure 9 immunofluorescence image of Parkin localization after ultrasound treatment;

[0036] Figure 10 image of mitochondria, ubiquitination and Parkin localization;

[0037] Figure 11 image of MCL-1 protein change;

[0038] Figure 12 image of apoptosis change after ultrasound treatment;

[0039] Figure 13 image of mitochondrial membrane potential change after ultrasound treatment;

[0040] Figure 14 image of tumor volume change of 4T1 tumor-bearing mice during BCT: Yb ultrasound treatment;

[0041] Figure 15 image of hematoxylin and eosin (H&E) staining of tumor tissue section after BCT: Yb ultrasound treatment. DETAILED DESCRIPTION

[0042] The application provides a preparation method of a sound electricity Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticle, which comprises the following steps:

[0043] 1) stirring and mixing a titanium tetrachloride solution and a mixed reagent solution to obtain a stirring and mixing liquid;

[0044] The concentration of the titanium tetrachloride solution is 0.9 mmol / ml;

[0045] The molar content of barium chloride in 30 ml of the mixed reagent solution is 12.75 mmol, the molar content of calcium chloride is 2.25 mmol, and the molar content of ytterbium chloride is 1 mmol;

[0046] 2) mixing the stirring and mixing liquid with sodium hydroxide and polyvinylpyrrolidone and then performing heat treatment to obtain a heat-treated product;

[0047] 3) performing solid-liquid separation on the heat-treated product obtained in the step 2) to obtain a solid, washing the solid to neutral, drying, and then obtaining a sound electricity Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticle.

[0048] The present application stirs and mixes titanium tetrachloride solution and mixed reagent solution to obtain a stirred and mixed solution; the concentration of the titanium tetrachloride solution is 0.9 mmol / ml; the molar content of barium chloride in 30 ml of the mixed reagent solution is 12.75 mmol, the molar content of calcium chloride is 2.25 mmol, and the molar content of ytterbium chloride is 1 mmol. In the present application, the volume ratio of the titanium tetrachloride solution to the mixed reagent solution is preferably 1:3. In the present application, the stirring and mixing time is preferably 30 min.

[0049] The present application mixes the stirred and mixed solution with sodium hydroxide and polyvinylpyrrolidone and then performs heat treatment to obtain a heat-treated product. In the present application, the volume of the stirred and mixed solution to the mass of sodium hydroxide and the mass of polyvinylpyrrolidone are preferably 40 ml:3.6 g:1.2 g. In the present application, the molecular weight of the polyvinylpyrrolidone is preferably 8000 Da. In the present application, the mixing time is preferably 30 min. In the present application, the heat treatment conditions are preferably including a temperature of 200℃ and a time of 20 h.

[0050] The present application performs solid-liquid separation on the obtained heat-treated product to obtain a solid, washes the solid to neutral, and then dries to obtain the piezoelectric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles. In the present application, the washing to neutral is preferably using deionized water and anhydrous ethanol. In the present application, the drying conditions are preferably including a temperature of 80℃ and a time of 12 h.

[0051] The present application also provides the piezoelectric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles prepared by the preparation method.

[0052] The present application also provides the piezoelectric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles in the preparation of a drug for promoting post-translational modification of tumor cells.

[0053] In order to further illustrate the present application, the present application is described in detail below in conjunction with examples, but they should not be understood as limiting the scope of protection of the present application.

[0054] Example 1

[0055] Ba 0.85 Ca 0.15 Ti0.9 Yb 0.1 Preparation of BCT:Yb NPs, the procedure is as follows:

[0056] 1) BCT:Yb NPs were synthesized by hydrothermal reaction. 1.707 g (9 mmol) of TiCl4 powder was dissolved in 10 mL of anhydrous ethanol to prepare a TiCl4 anhydrous ethanol solution. Then, 3.114 g (12.75 mmol) of BaCl2·2H2O and 0.166 g (2.25 mmol) of CaCl2 and 0.387 g (1 mmol) of YbCl3 solid powder were dissolved in 30 mL of deionized water to prepare a mixed solution. 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles. During the synthesis, 1.707 g (9 mmol) of TiCl4 powder was dissolved in 10 mL of anhydrous ethanol to prepare a TiCl4 anhydrous ethanol solution. Then, 3.114 g (12.75 mmol) of BaCl2·2H2O and 0.166 g (2.25 mmol) of CaCl2 and 0.387 g (1 mmol) of YbCl3 solid powder were dissolved in 30 mL of deionized water to prepare a mixed solution.

[0057] 2) After the two clear solutions were mixed uniformly by magnetic stirring in a 100 mL round-bottom flask for 10 minutes, 3.6 g of NaOH and 1.2 g of polyvinylpyrrolidone (PVP, molecular weight 8000 Da) were added, and stirring was continued for 30 minutes. Finally, the suspension was transferred to a 50 mL stainless steel autoclave lined with tetrafluoroethylene, and reacted at 200 °C for 20 hours.

[0058] 3) After the reaction was completed, the obtained precipitate was repeatedly washed with deionized water and anhydrous ethanol until pH = 7.0, and then dried in an oven at 80 °C for 12 h to obtain BCT:Yb NPs. BCT:Yb NPs with a size of 96.87 ± 7.26 nm were prepared, as shown in FIG. 1. Scanning electron microscope imaging of BCT:Yb NPs is shown in FIG. 2, and element mapping shows that the distributions of Ba, Ca, Ti, Yb, and O within the composite structure are uniform, as shown in FIG. 3. The x-ray diffraction pattern clearly shows the crystal structure of the prepared nanoparticles. The positions of different peaks are consistent with the standard card of tetragonal phase BTO, as shown in FIG. 4. The chemical composition and oxidation state of BCT:Yb were studied by x-ray photoelectron spectroscopy, as shown in FIG. 5. Fourier transform infrared spectroscopy further proves the successful synthesis of BCT:Yb, as shown in FIG. 6. In the Raman spectrum, the characteristic peaks of BTO at 307 cm-1 and 715 cm-1 are tetragonal phase BTO, as shown in FIG. 7. 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles (BCT:Yb NPs). BCT:Yb NPs with a size of 96.87 ± 7.26 nm were prepared, as shown in FIG. 1. Scanning electron microscope imaging of BCT:Yb NPs is shown in FIG. 2, and element mapping shows that the distributions of Ba, Ca, Ti, Yb, and O within the composite structure are uniform, as shown in FIG. 3. The x-ray diffraction pattern clearly shows the crystal structure of the prepared nanoparticles. The positions of different peaks are consistent with the standard card of tetragonal phase BTO, as shown in FIG. 4. The chemical composition and oxidation state of BCT:Yb were studied by x-ray photoelectron spectroscopy, as shown in FIG. 5. Fourier transform infrared spectroscopy further proves the successful synthesis of BCT:Yb, as shown in FIG. 6. In the Raman spectrum, the characteristic peaks of BTO at 307 cm-1 and 715 cm-1 are tetragonal phase BTO, as shown in FIG. 7. Figures 1-2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 -1 -1 Figure 8 ​​​​​​​​as shown.

[0059] Example 2

[0060] Experimental procedures for the experiment that ultrasound treatment of BCT: Yb NPs prepared in Example 1 causes Parkin translocation to mitochondria, causes ubiquitination degradation of MCL-1, promotes apoptosis are as follows:

[0061] 1) Hela cells were incubated overnight in 35 mm confocal dishes, 1 μg of Parkin eukaryotic expression vector (Parkin / PEGFP-N1) plasmid or control vector was transfected into cells with Lipofectamine 3000 according to the manufacturer's protocol, 48 h later, PBS, BaTiO3 (BTO), Ba 0.70 Ca 0.30 TiO3 (BCT), BCT: Yb 50 μg / mL were added for 6 h, and ultrasound (1.5 W / cm 2 , 1 MHz, 50% duty cycle) for 3 minutes. After 24 h, the localization of Parkin and the mitochondrial marker protein Tom20 was detected using a fluorescence confocal laser scanning microscope. In the control group, GFP-Parkin was widely distributed in the cytoplasm and did not overlap with mitochondria, while when HeLa cells were treated with BCT: Yb under ultrasound (US) stimulation, Parkin was rapidly recruited to mitochondria. The results showed that there were more yellow spots in the BCT: Yb+US group of cells, representing the colocalization of Parkin and the mitochondrial marker protein Tom20, and BCT: Yb and US stimulation promoted the translocation of Parkin from the cytoplasm to mitochondria as Figure 9 shown.

[0062] 2) Hela cells were incubated overnight in 35 mm confocal dishes, 1 μg of Parkin eukaryotic expression vector (Parkin / PEGFP-N1) plasmid or control vector was transfected into cells with Lipofectamine 3000 according to the manufacturer's protocol, 48 h later, PBS, BTO, BCT, BCT: Yb were added for 6 h, and ultrasound (1.5 W / cm 2 , 1 MHz, 50% duty cycle) for 3 minutes. After 24 h, the localization of Parkin protein, ubiquitination and the mitochondrial marker protein Tom20 was detected using a fluorescence confocal laser scanning microscope. In cells treated with BCT: Yb+us, there was colocalization between GFP-Parkin and ubiquitination in mitochondria, as Figure 10 shown, which suggested that the increase in mitochondrial ubiquitination might be related to Parkin.

[0063] 3) Hela cells were incubated overnight in 6-well plates, and 1 μg of Parkin eukaryotic expression vector (Parkin / PEGFP-N1) plasmid or control vector was transfected into cells with Lipofectamine 3000 according to the manufacturer's protocol. After 48 h, PBS, BTO, BCT, BCT: Yb were added for incubation for 6 h, and ultrasonic treatment (1.5 W / cm 2 , 1 MHz, 50% duty cycle) was performed for 3 min. After 24 h, flow cytometry apoptosis experiments were performed after staining with annexin V-APC and propidium iodide (PI), and the anti-tumor effect was observed. After US treatment, the cells obviously underwent apoptosis. The apoptosis rate of the BCT: Yb+US group was higher than that of the other groups, reaching 53.5%, as shown in Figure 11 , indicating that BCT: Yb-mediated treatment has a higher tumor killing effect.

[0064] 4) Hela cells were incubated overnight in 6-well plates, and 1 μg of Parkin eukaryotic expression vector (Parkin / PEGFP-N1) plasmid or control vector was transfected into cells with Lipofectamine 3000 according to the manufacturer's protocol. After 48 h, PBS, BTO, BCT, BCT: Yb were added for incubation for 6 h, and ultrasonic treatment (1.5 W / cm 2 , 1 MHz, 50% duty cycle) was performed for 3 min. After 24 h, proteins were extracted from each group, and Western Blotting was used to detect the expression of MCL-1 protein in each group. As shown in Figure 12 , compared with the BTO+US and BCT+US groups, the MCL-1 protein level in the HeLa cells was significantly reduced after BCT: Yb+US administration, indicating that the apoptosis caused by BCT: Yb combined with US may be related to mitochondrial MCL-1 protein ubiquitination.

[0065] Example 3

[0066] The steps of the experiment for testing the change in mitochondrial membrane potential in the BCT: Yb NPs prepared in Example 1 under ultrasonic treatment are as follows:

[0067] JC-1 probe was used to detect the mitochondrial membrane potential (ΔΨ) of Hela cells. Hela cells were seeded in 35 mm confocal dishes and incubated overnight. PBS, BTO, BCT, BCT: Yb were added for incubation for 6 h, and ultrasonic treatment (1.5 W / cm 2 , 1 MHz, 50% duty cycle) was performed for 3 min per well, and the cells were incubated for 4 h. JC-1 fluorescent dye was added, and the cells were incubated at 37°C for 20 min. After washing with cold PBS, the fluorescence intensity of each group was analyzed using a fluorescence confocal laser scanning microscope, as shown in Figure 13As shown in the diagram, JC-1 aggregates produce red fluorescence when the mitochondrial membrane potential is high. When the mitochondrial membrane potential is low, JC-1 exists as monomers and produces green fluorescence, indicating mitochondrial depolarization. The higher the ratio of green fluorescence to red fluorescence, the more pronounced the mitochondrial depolarization. The results showed that HeLa cells treated with BTO+US, BCT+US, and BCT:Yb+US all exhibited strong green fluorescence, while other groups showed strong red fluorescence.

[0068] Example 4

[0069] The experimental steps for evaluating the ultrasound treatment effect of BCT:Yb NPs prepared in Example 1 are as follows:

[0070] 1) Animal experiments were conducted using a breast cancer model constructed from subcutaneously implanted 4T1 cell-bearing BALB / c mice. 2 × 10⁻⁶ cells were subcutaneously injected into the right back of female BALB / c mice. 6 A mouse 4T1 breast cancer tumor model was successfully established using 4T1 cells. Tumor-bearing mice were randomly divided into 6 groups (n = 6): (1) PBS group; (2) BCT:Yb group; (3) PBS+US group; (4) BTO+US group; (5) BCT+US group; (6) BCT:Yb+US group. When the tumor grew to 100 mm... 3 Mice were injected with the above-mentioned groups. Except for groups (1) and (2), all other groups received ultrasound therapy at 1.5 W, 1.0 MHz, and 50% duty cycle 12 hours after the first intravenous injection of nanoparticles. The tumor volume of each group was recorded during the 15-day treatment period. Figure 14 As shown.

[0071] 2) To further elucidate the therapeutic effect of BCT:Yb NPs ultrasound, tumors from each group of mice were collected after treatment and prepared into 10 μm tissue sections. These sections were stained with eosin and hematoxylin. It was observed that the tumor tissue was significantly damaged after BCT:Yb NPs ultrasound treatment. Figure 15 As shown.

[0072] Ba prepared by this invention 0.85 Ca 0.15 Ti 0.9 Yb 0.1O3(BCT:Yb NPs), unlike traditional epigenetic small-molecule drugs, are activated only by ultrasound, avoiding off-target damage to normal cells. Positively charged BCT:Yb targets mitochondria due to electrostatic interactions with the mitochondrial surface. After BCT:Yb NPs depolarize the mitochondrial membrane potential under ultrasound stimulation, they trigger the translocation of Parkin from the cytoplasm to the outer mitochondrial membrane, leading to ubiquitination and cascade degradation of the anti-apoptotic protein MCL-1, resulting in cell apoptosis. This is mainly because under ultrasound stimulation, BCT:Yb NPs can consume H+ around the mitochondria, leading to a decrease in mitochondrial membrane potential and depolarization, followed by the recruitment and activation of Parkin and its ubiquitin E3 ligase activity. Our work provides a new non-drug and non-invasive method for post-translational modification of proteins, avoiding side effects associated with the use of traditional small-molecule drugs, and expanding new applications of nanomaterials in regulating epigenetic changes, etc.

[0073] Although the above embodiments make a detailed description of the present application, it is only a part of the embodiments of the present application, not all the embodiments, and people can also obtain other embodiments according to the present embodiments without creativity, which all belong to the protection scope of the present application.

Claims

1. A type of acoustic-electrical method that triggers post-translational modification. 0.85 Ca 0.15 Ti 0.9 Yb 0.1 The method for preparing O3 nanoparticles is characterized by, Includes the following steps: 1) Stir the titanium tetrachloride solution and the mixed reagent solution to obtain a stirred mixture; The concentration of the titanium tetrachloride solution was 0.9 mmol / ml; The molar content of barium chloride in each 30 ml mixed reagent solution is 12.75 mmol, the molar content of calcium chloride is 2.25 mmol, and the molar content of ytterbium trichloride is 1 mmol. 2) The stirred mixture is mixed with sodium hydroxide and polyvinylpyrrolidone and then subjected to heat treatment to obtain a heat-treated product; 3) Separate the heat-treated material obtained in step 2) from its solid state to obtain a solid. Wash the solid until it is neutral, and after drying, obtain the acoustic-electric Ba. 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles.

2. The preparation method according to claim 1, characterized in that, In step 1), the volume ratio of titanium tetrachloride solution to mixed reagent solution is 1:

3.

3. The preparation method according to claim 1, characterized in that, The mixing time for step 1) is 30 minutes.

4. The preparation method according to claim 1, characterized in that, In step 2), the volume ratio of the stirred mixture to the mass ratio of sodium hydroxide and polyvinylpyrrolidone is 40 ml: 3.6 g: 1.2 g. The molecular weight of the polyvinylpyrrolidone is 8000 Da.

5. The preparation method according to claim 1, characterized in that, The mixing time for step 2) is 30 minutes.

6. The preparation method according to claim 1, characterized in that, The conditions for heat treatment in step 2) include: a temperature of 200°C and a time of 20 hours.

7. The preparation method according to claim 1, characterized in that, Step 3) involves washing with deionized water and anhydrous ethanol until neutral.

8. The preparation method according to claim 1, characterized in that, The drying conditions in step 3) include: a temperature of 80°C and a time of 12 hours.

9. An acoustic-electric Ba obtained by the preparation method according to any one of claims 1 to 8 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles.

10. The acoustic-electric Ba obtained by the preparation method according to any one of claims 1 to 8 0.85 Ca 0.15 Ti 0.9 Yb 0.1 Application of O3 nanoparticles in the preparation of antitumor drugs.

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