Triggered post-translational modification acoustoelectric Ba0. 85Ca0. 15Ti0. 9Yb0. 1O3 nanoparticles as well as preparation method and application thereof

Abstract

The invention relates to the technical field of biology, in particular to acoustoelectric Ba0. 85Ca0. 15Ti0. 9Yb0. 1O3 nanoparticles capable of triggering post-translational modification as well as a preparation method and application of the acoustoelectric Ba0. 85Ca0. 15Ti0. 9Yb0.1 O3 nanoparticles. Stirring and mixing the titanium tetrachloride solution and the mixed reagent solution to obtain a stirred mixed solution; mixing the stirred mixed solution with sodium hydroxide and polyvinylpyrrolidone, and performing heat treatment to obtain a heat-treated substance; and carrying out solid-liquid separation on the heat-treated substance to obtain a solid, washing the solid to be neutral, and drying. The nanoparticles provided by the invention consume H < + > near mitochondria under ultrasonic stimulation, so that mitochondrial membrane potential depolarization is caused. After mitochondrial membrane potential depolarization, E3 ubiquitin ligase Parkin is transferred from cytoplasm to a mitochondrial outer membrane, and is massively gathered and accumulated on the mitochondrial outer membrane, so that ubiquitination modification and cascade degradation of mitochondrial outer membrane anti-apoptosis protein MCL-1 are caused, and cell apoptosis is promoted.

Description

Technical Field

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

[0002] Post-translational modification (PTM) is an important regulatory mechanism that alters protein properties by covalently attaching modified chemical groups to certain amino acid residues. PTMs regulate important physiological processes, such as signal transduction, metabolism, protein localization, and turnover, and have broad clinical significance in diseases such as cardiovascular and metabolic disorders and cancer. PTMs are a crucial aspect of epigenetic regulation of life. They are typically catalyzed by enzymes and serve as major regulators of protein activity. They include various modifications, such as ubiquitination, methylation, acetylation, and glycosylation. Among them, protein ubiquitination is a dynamic post-translational modification process based on a molecular cascade, involved in virtually all life processes in eukaryotes. Ubiquitination is a multistep process mediated by three classes of enzymes: ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Ubiquitin is first activated by E1 and then transferred to the E2 conjugating enzyme. Subsequently, the E3 ubiquitin ligase interacts with the ubiquitin-loaded E2 and the substrate protein, forming an isopeptide bond between the ubiquitin C-terminus and the substrate's lysine. This process regulates protein stability, localization, and function, ultimately influencing fundamental cellular processes such as cell cycle progression and DNA repair. Therefore, post-translational modifications have a broad impact on the regulation of cell fate. They can lead to pathway activation or repression, assembly or degradation of protein complexes, and protein accumulation or relocalization.

[0003] Currently, many small molecule compounds have been developed in the laboratory to achieve post-translational modifications to regulate cell fate. In 2004, the first epigenetic drug approved by the US Food and Drug Administration (FDA) was azacitidine (Vidaza), which inhibits the DNMT1 enzyme responsible for maintaining DNA methylation, leading to DNA demethylation, for the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. HDAC inhibitors (HDACi) can regulate histone post-translational modifications and regulate protein expression at the epigenetic level. HDACi can regulate metabolic pathway proteins by increasing histone acetylation or reverse epithelial-mesenchymal transition by regulating ubiquitination pathways. The first HDAC inhibitor was hydroxyaniline 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 in a variety of transformed cells. However, these drugs have side effects such as leukopenia, neutropenia, and thrombocytopenia, as well as gastrointestinal symptoms such as nausea, vomiting, diarrhea, and constipation. This may be because the drug targets are distributed throughout the body, so off-target effects of the drugs explain the occurrence of adverse reactions. These cases verify that it is possible to regulate cellular post-translational modification processes. 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 of the Invention

[0004] In order to solve the above problems, the present invention provides a Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles, their preparation methods, and applications report a non-drug strategy based on acoustic-electric nanomaterials for directly manipulating cellular post-translational modifications. This work provides the earliest example of non-drug nanoparticles directly manipulating changes in post-translational modifications. It enables precise targeting of drug sites and targets, addresses the limitations of small molecule compounds, and reveals a new mechanism for direct nanoparticle manipulation of epigenetic modifications.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] The present invention provides a method for triggering post-translational modification of the acoustic-electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 The preparation method of O3 nanoparticles comprises the following steps:

[0007] 1) stirring and mixing the titanium tetrachloride solution and the mixed reagent solution to obtain a stirred 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 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 trichloride is 1 mmol;

[0010] 2) mixing the stirred mixed liquid with sodium hydroxide and polyvinyl pyrrolidone and then heat-treating the mixture to obtain a heat-treated product;

[0011] 3) The heat-treated product obtained in step 2) is separated into solid and liquid to obtain a solid, which is then washed to neutrality and dried to obtain an acoustic electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles.

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

[0013] Preferably, the stirring and mixing time in step 1) is 30 minutes.

[0014] Preferably, in step 2), the ratio of the volume of the stirred mixture to the mass of sodium hydroxide and the mass of polyvinyl pyrrolidone is 40 ml:3.6 g:1.2 g;

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

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

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

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

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

[0020] The present invention provides an acoustic-electric Ba prepared by the preparation method of the above technical solution. 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles.

[0021] The present invention also provides the acoustic-electric Ba 0.85 Ca 0.15 Ti 0.9Yb 0.1 Application of O3 nanoparticles in the preparation of drugs that promote post-translational modification of tumor cells.

[0022] Beneficial effects of the present invention:

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

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

[0025] 3) BCT: Yb piezoelectric nanomaterials promote the transfer of Parkin from the cytoplasm to the mitochondria by promoting the depolarization of the mitochondrial membrane potential under ultrasound stimulation, leading to the recruitment and accumulation of Parkin on the mitochondria, thereby causing the ubiquitination and degradation of the mitochondrial outer membrane anti-apoptotic protein Mcl-1, thereby achieving control of cancer cell growth. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments are briefly introduced below.

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

[0028] Figure 2 This is a high-magnification TEM of BCT:Yb nanoparticles;

[0029] Figure 3 This is a scanning electron microscope image of BCT:Yb nanoparticles;

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

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

[0032] Figure 6 is the X-ray photoelectron spectrum of BCT:Yb;

[0033] Figure 7 is the infrared spectrum of BCT:Yb;

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

[0035] Figure 9 Immunofluorescence images of Parkin localization after ultrasound treatment;

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

[0037] Figure 11 This is an image showing changes in MCL-1 protein;

[0038] Figure 12 This is an image of cell apoptosis changes after ultrasound treatment;

[0039] Figure 13 This is the image of mitochondrial membrane potential changes after ultrasound treatment;

[0040] Figure 14 This is an image of tumor volume changes in 4T1 tumor-bearing mice during BCT:Yb ultrasound treatment;

[0041] Figure 15 These are hematoxylin and eosin (H&E) stained images of tumor tissue sections after BCT:Yb ultrasound treatment. DETAILED DESCRIPTION

[0042] The present invention provides a method for triggering post-translational modification of the acoustic-electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 The preparation method of O3 nanoparticles comprises the following steps:

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

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

[0045] The molar content of barium chloride in each 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 trichloride is 1 mmol;

[0046] 2) mixing the stirred mixed liquid with sodium hydroxide and polyvinyl pyrrolidone and then heat-treating the mixture to obtain a heat-treated product;

[0047] 3) The heat-treated product obtained in step 2) is separated into solid and liquid to obtain a solid, which is then washed to neutrality and dried to obtain an acoustic electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles.

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

[0049] The present invention is to mix the stirred mixed liquid with sodium hydroxide and polyvinyl pyrrolidone and then heat treat the mixture to obtain a heat-treated product. In the present invention, the volume of the stirred mixed liquid to the mass of sodium hydroxide and polyvinyl pyrrolidone is preferably 40 ml:3.6 g:1.2 g. In the present invention, the molecular weight of the polyvinyl pyrrolidone is preferably 8000 Da. In the present invention, the mixing time is preferably 30 minutes. In the present invention, the heat treatment conditions preferably include: a temperature of 200° C. and a time of 20 hours.

[0050] The present invention separates the heat-treated product into solid and liquid to obtain a solid, washes the solid to neutrality, and then dries the solid to obtain an acoustic electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles. In the present invention, deionized water and anhydrous ethanol are preferably used for washing until neutral. In the present invention, the drying conditions preferably include: a temperature of 80°C and a drying time of 12 hours.

[0051] The present invention also provides an acoustic-electric Ba prepared by the preparation method described in the above technical solution. 0.85 Ca 0.15 Ti 0.9 Yb 0.1 O3 nanoparticles.

[0052] The present invention also provides the acoustic-electric Ba 0.85 Ca 0.15 Ti 0.9 Yb 0.1 Application of O3 nanoparticles in the preparation of drugs that promote post-translational modification of tumor cells.

[0053] In order to further illustrate the present invention, the present invention is described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0054] Example 1

[0055] Ba 0.85 Ca 0.15 Ti 0.9 Yb0.1 Preparation of O3 nanoparticles (BCT:Yb NPs) is as follows:

[0056] 1) Synthesis of Ba by hydrothermal reaction 0.85 Ca 0.15 Ti 0.9 Yb 0.1 During the synthesis process, 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, 0.166 g (2.25 mmol) of CaCl2, and 0.387 g (1 mmol) of YbCl3 solid powders were dissolved in 30 ml of deionized water to prepare a mixed solution.

[0057] 2) The two clear solutions were mixed uniformly in a 100 mL round-bottom flask under magnetic stirring for 10 minutes. Then, 3.6 g of NaOH and 1.2 g of polyvinylpyrrolidone (PVP, molecular weight 8000 Da) were added and stirring 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, the precipitate was washed repeatedly with deionized water and anhydrous ethanol until the pH value was 7.0, and then dried in an oven at 80°C for 12 hours to obtain Ba 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±7.26nm were prepared, as shown in Figure 1-2 Scanning electron microscopy imaging of BCT:Yb NPs is shown in Figure 3 As shown, element mapping shows that Ba, Ca, Ti, Yb and O are evenly distributed in the composite structure. Figure 4 As shown. The X-ray diffraction pattern clearly shows the crystal structure of the prepared nanoparticles. The positions of the different peaks are consistent with the standard card of tetragonal BTO as shown Figure 5 The chemical composition and oxidation state of BCT:Yb were studied by X-ray photoelectron spectroscopy. Figure 6 As shown. Fourier transform infrared spectroscopy further confirmed the successful modification of PEMAN surface with hexadecyltrimethylammonium bromide (CTAB). Figure 7 As shown. In the Raman spectrum, BTO has a -1 and 715cm -1 The characteristic peak at is the tetragonal BTO. Figure 8 shown.

[0059] Example 2

[0060] The experimental steps for ultrasound treatment of BCT:Yb NPs prepared in Example 1 to induce Parkin to transfer to mitochondria, induce ubiquitination and degradation of MCL-1, and promote cell apoptosis are as follows:

[0061] 1) Hela cells were incubated overnight in a 35 mm confocal culture dish, and 1 μg of Parkin eukaryotic expression vector (Parkin / PEGFP-N1) plasmid or control vector was transfected into the cells using Lipofectamine 3000 according to the manufacturer's protocol. After 48 h, PBS, BaTiO3 (BTO), Ba 0.70 Ca 0.30 TiO3(BCT), BCT:Yb 50μg / mL were incubated for 6h, and ultrasonication (1.5W / cm 2 ,1MHz,50% duty cycle) for 3 minutes. After 24h, the localization of Parkin and 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 the mitochondria. However, when HeLa cells were treated with BCT:Yb under ultrasound (US) stimulation, Parkin was rapidly recruited to the mitochondria. The results showed that there were more yellow spots in the cells of the BCT:Yb+US group, indicating that Parkin and the mitochondrial marker protein Tom20 were co-localized. BCT:Yb and US stimulation promoted the transfer of Parkin from the cytoplasm to the mitochondria. Figure 9 shown.

[0062] 2) Hela cells were incubated overnight in a 35 mm confocal culture dish, and 1 μg of Parkin eukaryotic expression vector (Parkin / PEGFP-N1) plasmid or control vector was transfected into the cells using Lipofectamine 3000 according to the manufacturer's protocol. After 48 h, PBS, BTO, BCT, and BCT:Yb were added and incubated for 6 h. Ultrasound (1.5 W / cm 2 ,1MHz,50% duty cycle) for 3 minutes. After 24 hours, the localization of Parkin protein, ubiquitination and mitochondrial marker protein Tom20 was detected using fluorescence confocal laser scanning microscopy. In BCT:Yb+us treated cells, there was colocalization between GFP-Parkin and ubiquitination in mitochondria, such as Figure 10 This suggests that the increase in mitochondrial ubiquitination may 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 the cells using Lipofectamine 3000 according to the manufacturer's protocol. After 48 h, PBS, BTO, BCT, and BCT:Yb were added and incubated for 6 h. Ultrasonication (1.5 W / cm 2 , 1MHz, 50% duty cycle) for 3 minutes. After 24 hours, flow cytometry apoptosis assay was performed after staining with annexin V-APC and propidium iodide (PI) to observe its anti-tumor effect. After US treatment, cells showed obvious apoptosis. The apoptosis rate of cells in the BCT:Yb+US group was higher than that in other groups, reaching 53.5%. Figure 11 As shown, this indicates that BCT:Yb-mediated therapy has a high 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 the cells using Lipofectamine 3000 according to the manufacturer's protocol. After 48 h, PBS, BTO, BCT, and BCT:Yb were added and incubated for 6 h. Ultrasonication (1.5 W / cm 2 ,1MHz,50% duty cycle) for 3 minutes. After 24 hours, the proteins of each group were extracted and the expression of MCL-1 protein in each group was detected by Western Blotting. Figure 12 As shown in the results, the MCL-1 protein level in HeLa cells was significantly decreased after BCT:Yb+US administration compared with the BTO+US and BCT+US groups, indicating that the apoptosis induced by BCT:Yb combined with US may be related to the ubiquitination of mitochondrial MCL-1 protein.

[0065] Example 3

[0066] The experimental steps for changing mitochondrial membrane potential by ultrasound treatment of BCT:Yb NPs prepared in Example 1 are as follows:

[0067] The mitochondrial membrane potential (ΔΨ) of Hela cells was measured using a JC-1 probe. Hela cells were seeded in 35 mm confocal microplates and cultured overnight. PBS, BTO, BCT, and BCT:Yb were added and incubated for 6 h. Each well was sonicated (1.5 W / cm 2 ,1MHz,50% duty cycle) for 3min and let it stand for 4h. JC-1 fluorescent dye was added and incubated at 37℃ for 20min. After washing with cold PBS, the fluorescence intensity of each group was analyzed using a fluorescence confocal laser scanning microscope, as shown in Figure 13When the mitochondrial membrane potential is high, JC-1 aggregates produce red fluorescence. When the mitochondrial membrane potential is low, JC-1 is monomeric and produces green fluorescence, indicating mitochondrial depolarization. The greater the ratio of green fluorescence to red fluorescence, the more pronounced mitochondrial depolarization. The results showed that HeLa cells treated with BTO+US, BCT+US, and BCT:Yb+US all exhibited strong green fluorescence, while the other groups exhibited 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 experiment: BALB / c mice bearing 4T1 cells were used as an example to construct a breast cancer model. 2×10 6 4T1 cells were used to successfully establish a mouse 4T1 breast cancer tumor model. The 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 The mice were injected with the above groups. Except for groups (1) and (2), the rest of the groups received ultrasound treatment at 1.5W, 1.0MHz, 50% duty cycle 12 hours after the first intravenous injection of nanoparticles. The tumor volume of each group during the 15-day treatment was calculated as follows: Figure 14 shown.

[0071] 2) To further illustrate the therapeutic effect of BCT:Yb NPs ultrasound, the tumors of each group of mice were collected after treatment and cut into 10 μm tissue sections. The 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 shown.

[0072] Ba prepared by the present invention 0.85 Ca 0.15 Ti 0.9 Yb 0.1O3(BCT:Yb NPs), unlike traditional epigenetic small molecule drugs, acoustic electric nanorobots are activated only by ultrasound, avoiding off-target damage to normal cells. Positively charged BCT:Yb is targeted to 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 mitochondrial outer 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 mitochondria, resulting in a decrease and depolarization of the mitochondrial membrane potential, followed by the recruitment of Parkin and activation of its ubiquitin E3 ligase activity. Our work provides a new non-drug and non-invasive approach for protein post-translational modification, avoiding the side effects associated with the use of traditional small molecule drugs, and expands new applications of nanomaterials in regulating epigenetic changes.

[0073] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A sonoelectric Ba-like device that triggers post-translational modification 0.85 Ca 0.15 Ti 0.9 Yb 0.1 The method for preparing O3 nanoparticles is characterized in that: The following steps are involved: 1) stirring and mixing the titanium tetrachloride solution and the mixed reagent solution to obtain a stirred mixed solution; The concentration of the titanium tetrachloride solution is 0.9 mmol / ml; The molar content of barium chloride in each 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 trichloride is 1 mmol; 2) mixing the stirred mixed liquid with sodium hydroxide and polyvinyl pyrrolidone and then heat-treating the mixture to obtain a heat-treated product; 3) The heat-treated product obtained in step 2) is separated into solid and liquid to obtain a solid, which is then washed to neutrality and dried to obtain an 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 the titanium tetrachloride solution to the mixed reagent solution is 1:

3.

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

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

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

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

7. The preparation method according to claim 1, characterized in that In step 3), the mixture is washed 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 drying time of 12 hours.

9. An acoustic electric Ba prepared 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 according to claim 9 0.85 Ca 0.15 Ti 0.9 Yb 0.1 Application of O3 nanoparticles in the preparation of drugs that promote post-translational modification of tumor cells.

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