Method for constructing barium titanate piezoelectric nano-enzyme in-situ based on mesoporous silicon and application
Iron-doped barium titanate piezoelectric nanozymes were constructed by gradient calcination on mesoporous silica carriers. Combining piezoelectric and enzyme catalytic properties, the problem of insufficient •OH generation in the barium titanate piezoelectric catalytic system was solved, achieving highly efficient tumor treatment.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NORTHEAST FORESTRY UNIV
- Filing Date
- 2026-03-12
- Publication Date
- 2026-06-05
AI Technical Summary
The amount of hydroxyl radicals (•OH) generated by existing barium titanate piezoelectric catalytic systems is insufficient to meet the needs of efficient tumor treatment, and a single catalytic system cannot achieve synergistic improvement of •OH generation efficiency through multiple pathways.
Using mesoporous silica as a carrier, iron-doped barium titanate piezoelectric nanozymes were constructed in situ via gradient calcination. Combining piezoelectric catalysis and enzyme-like catalysis, iron doping was used to optimize the crystal structure and electron configuration, enhancing catalytic performance and enabling the generation of •OH through multiple pathways.
Under ultrasound stimulation, the material can convert endogenous H2O in tumor cells into •OH and •O2-, and further convert them into H2O2 and •OH through POD-like and SOD-like activities, thereby enhancing the tumor-killing effect and achieving highly efficient tumor treatment.
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Figure CN122140930A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of nanozyme preparation, and in particular to a method and application of in-situ construction of barium titanate piezoelectric nanozymes based on mesoporous silica. Background Technology
[0002] In recent years, barium titanate nanomaterials have shown great potential in the field of tumor catalytic therapy due to their unique perovskite structure and excellent piezoelectric catalytic properties. Piezoelectric catalysis can generate piezoelectric potentials through mechanical stimulation such as ultrasound and mechanical vibration, driving catalytic reactions to efficiently produce reactive oxygen species (ROS) for tumor killing, providing a new pathway for deep tumor treatment. Simultaneously, the tumor microenvironment contains abundant H2O molecules that generate hydroxyl radicals (•OH) through piezoelectric catalysis. •OH, as a highly reactive species among ROS, is a core effector in tumor therapy, enabling efficient tumor killing. However, the •OH content generated by a single barium titanate piezoelectric catalytic system is insufficient to meet the actual needs of efficient tumor treatment. Therefore, constructing a multifunctional barium titanate piezoelectric catalytic system to synergistically enhance the •OH generation efficiency through multiple pathways is of great significance for improving the efficacy of tumor catalytic therapy. Piezoelectric nanozymes combine piezoelectric catalytic properties with enzyme-like catalytic properties, providing a new research approach to overcome the aforementioned challenges. Therefore, we developed a method and application for in-situ construction of barium titanate piezoelectric nanozymes based on mesoporous silica, offering an effective solution to the problems mentioned above: iron doping optimizes the crystal structure and electron configuration through lattice control, improving charge separation efficiency and enhancing the piezoelectric catalytic production of •OH. Simultaneously, iron doping endows the material with superior peroxidase (POD) and superoxide dismutase (SOD)-like activities. The SOD-like activity enhances the production of superoxide anions (•O2) generated by piezoelectric catalysis. - It is converted into H2O2, which together with the endogenous H2O2 in the tumor microenvironment serves as a substrate for a POD-mediated Fenton-like reaction, generating •OH. The piezoelectric catalysis and multi-enzyme catalysis work synergistically to increase the content of •OH, which has a strong tumor-killing effect, thereby enhancing the anti-tumor effect. Summary of the Invention
[0003] The purpose of this invention is to provide a method and application for in-situ construction of barium titanate piezoelectric nanoenzymes based on mesoporous silica, thereby solving the aforementioned problems existing in the prior art.
[0004] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0005] A method for in-situ construction and application of barium titanate piezoelectric nanoenzymes based on mesoporous silica includes the following steps:
[0006] S1, mesoporous silica (MSNs) was prepared by template method using hexadecyltrimethyl-p-toluenesulfonium, triethanolamine, 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate and ethyl orthosilicate as raw materials.
[0007] S2, using MSNs and titanium, barium and iron ions as raw materials, prepared iron-doped barium titanate piezoelectric nanozymes (denoted as Fe-BaTiO3) in situ within confined mesoporous silica using a gradient calcination method. These nanozymes possess piezoelectric catalytic properties and various enzyme catalytic activities (POD-like and SOD-like).
[0008] Preferably, the mesoporous silica described in step S1 is characterized in that the MSNs described in step S1 are prepared by a template method. 0.8–1.2 g of hexadecyltrimethyl-p-toluenesulfonium, 0.1–0.2 g of triethanolamine, and 10–15 mg of 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate are dissolved in distilled water and stirred at 80–120 °C for 1–3 h. Then, 7–11 mL of ethyl orthosilicate is added, and stirring continues for 1–3 h. Anhydrous ethanol is then rapidly added to quench the reaction. The product is centrifuged and washed, and then dispersed in anhydrous ethanol for 20–26 h to remove the template hexadecyltrimethyl-p-toluenesulfonium. Finally, the product is centrifuged, washed, and dried to obtain the solid product, which is the MSNs.
[0009] Preferably, step S2 specifically includes: dispersing 25-45 mg of MSNs in anhydrous ethanol, adding a mixed solution containing urea and ammonium chloride and stirring for 2-3 h, then adding 0.2-0.3 g of titanium acetylacetonate and continuing stirring for 5-8 h, followed by adding 0.1-0.2 g of barium chloride and stirring for 12 h, then adding 40-50 mg of ferric chloride hexahydrate and continuing stirring for 10-12 h. The resulting product is dried in an oven at 40-60 ℃, the solid product is thoroughly ground in a mortar, and finally subjected to gradient calcination in a muffle furnace at a maximum temperature of 400-500 ℃ for 4-6 h to obtain the final product Fe-BaTiO3.
[0010] Another objective of this invention is to provide piezoelectric and enzyme-like catalytic properties of barium titanate piezoelectric nanozymes constructed in situ from mesoporous silica.
[0011] The beneficial effects of this invention are:
[0012] This invention provides a method and application for in-situ construction of barium titanate piezoelectric nanozymes based on mesoporous silica. Using MSNs as a carrier, titanium acetylacetonate as the titanium source, barium chloride as the barium source, and ferric chloride hexahydrate as the iron source, the process involves stirring for 24 h followed by gradient calcination for 6 h to synthesize iron-doped barium titanate piezoelectric nanozymes grown in situ within the pores of MSNs. The prepared material exhibits piezoelectric catalytic activity, capable of converting endogenous H2O in tumor cells to •OH and O2 to •O2 under ultrasonic stimulation. - It also possesses POD-like and SOD-like activities, and can utilize SOD-like activities to convert •O2 -The process involves converting the generated H2O2 into H2O2, alleviating the H2O2 deficiency within the tumor microenvironment. Then, utilizing POD-like activity, the generated H2O2 and endogenous tumor-derived H2O2 are converted into •OH, achieving a piezoelectric catalysis and enzyme cascade reaction to further increase the •OH level, efficiently killing tumor cells and inducing tumor cell death. This strategy allows for the in-situ development of iron-doped barium titanate piezoelectric nanozymes that simultaneously achieve sonodynamic catalytic therapeutic performance and enzyme catalytic therapeutic performance within the channels of MSNs. Attached Figure Description
[0013] Figure 1 The image shows a scanning electron microscope image of the MSNs obtained in Example 1.
[0014] Figure 2 The N2 adsorption-desorption isotherms (a) and pore size distribution (b) curves of MSNs and Fe-BaTiO3 prepared in Example 1 are shown.
[0015] Figure 3 The image shown is a transmission electron microscope image of the Fe-BaTiO3 prepared in Example 1.
[0016] Figure 4 The images shown are high-angle annular dark-field scanning transmission electron microscope images and energy dispersive spectroscopy elemental distribution maps of Fe-BaTiO3 prepared in Example 1.
[0017] Figure 5 To determine whether p-benzoquinone (BQ) was added to the Fe-BaTiO3 prepared in Example 1 under ultrasonic irradiation to capture •O2. - This resulted in a time-dependent oxidation spectrum of 3,3,5,5-tetramethylbenzidine (TMB).
[0018] Figure 6 The POD-like enzyme catalytic activity of Fe-BaTiO3 prepared in Example 1 was detected by TMB;
[0019] Figure 7 The SOD-like enzyme catalytic activity of Fe-BaTiO3 prepared in Example 1 was detected by nitrotetrazole blue (NBT).
[0020] Figure 8 The TMB time-dependent oxidation spectrum of Fe-BaTiO3 prepared in Example 1 under ultrasonic irradiation produces •OH; Detailed Implementation
[0021] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.
[0022] Example 1
[0023] This embodiment provides a method for preparing barium titanate piezoelectric nanoenzymes based on in-situ mesoporous silica, which includes the following steps:
[0024] (1) Preparation of MSNs:
[0025] Dissolve 0.96 g of hexadecyltrimethyl-p-toluenesulfonium, 0.105 g of triethanolamine, and 10 mg of 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate in 50 mL of distilled water. After stirring at 80 °C for 1 h, add 7.8 mL of ethyl orthosilicate and continue stirring for 2 h. Then, centrifuge the product at 8000 rpm / min for 5 min, wash twice with anhydrous ethanol and water, respectively. Disperse the product in 150 mL of anhydrous ethanol for 24 h to remove the template hexadecyltrimethyl-p-toluenesulfonium. After centrifugation at 10000 rpm / min for 10 min, wash twice with anhydrous ethanol and dry. The obtained solid is MSNs.
[0026] The morphology of the prepared MSNs was observed using a scanning electron microscope, such as... Figure 1 As shown in the figure, the MSNs have a spherical structure with a uniform particle size distribution of approximately 120 nm. N2 adsorption and desorption tests were conducted, and the results were obtained from... Figure 2 As shown in figure a, it is proven that the surface has a distinct mesoporous structure, and the specific surface area of MSNs is found to be 229.3 m². 2 g -1 , Figure 2 The pore size distribution curve of MSNs in b proves that the average pore size is 14.43 nm.
[0027] (2) Preparation of iron-doped barium titanate piezoelectric nanozymes based on in-situ construction of mesoporous silica: 30 mg MSNs were dispersed in anhydrous ethanol, and then a mixed solution containing 2.7 g urea and 0.54 g ammonium chloride (solvents were 5 mL distilled water and 5 mL anhydrous ethanol) was added. After stirring for 3 h, 0.2293 g titanium acetylacetonate was added and stirring was continued for 8 h. Then 0.1822 g barium chloride was added and stirred for 12 h. Then 40.5 mg ferric chloride hexahydrate was added and stirring was continued for 12 h. The obtained product was dried in an oven at 60 ℃. The solid product was thoroughly ground in a mortar and finally calcined in a muffle furnace at a heating rate of 3 ℃ / min. The temperature was 110 ℃ for 2 h, 200 ℃ for 2 h, 300 ℃ for 2 h, and the maximum temperature was 400 ℃ for 6 h to obtain the final product Fe-BaTiO3.
[0028] The morphology of the material was characterized using transmission electron microscopy, and the resulting transmission electron microscopy images are shown below. Figure 3As shown, Fe-BaTiO3 exhibits a uniformly dispersed spherical structure with a particle size of approximately 120 nm. N2 adsorption and desorption tests were conducted, and the results were obtained from... Figure 2 As shown in figure a, the surface exhibits a distinct mesoporous structure, and the specific surface area of Fe-BaTiO3 is determined to be 48.7 m². 2 g -1 , Figure 2 The pore size distribution curve of MSNs in section b proves that the average pore size is 8.44 nm. The decrease in specific surface area and average pore size proves that Fe-BaTiO3 grows in situ within the pores of MSNs. Figure 4 High-angle annular dark-field scanning transmission electron microscopy images and elemental mapping spectra show that Si, O, Ba, Ti, and Fe are uniformly distributed in the material, further confirming the in-situ growth of Fe-BaTiO3.
[0029] Figure 5 To determine whether BQ trapping O2 was added to the Fe-BaTiO3 prepared in Example 1 under ultrasonic irradiation. - This led to a time-dependent oxidation profile of TMB; oxidation experiments of TMB were conducted using BQ as a trapping agent. Due to •O2 - Due to the oxidation of ROS, the absorbance of TMB increases. Under dark conditions without the addition of BQ, the absorbance of TMB increases rapidly. After adding BQ to the Fe-BaTiO3 solution, the absorbance increases due to the capture of •O2 by BQ. - Compared with the absence of BQ, the TMB absorbance at 652 nm was significantly reduced.
[0030] Figure 6 The POD-like catalytic activity of the prepared Fe-BaTiO3 was detected using TMB. The curves show a significant increase in absorbance at 652 nm after Fe doping, indicating that Fe doping significantly enhances the POD-like activity.
[0031] Figure 7 The SOD-like catalytic activity of the prepared Fe-BaTiO3 was detected using NBT. Compared with BaTiO3, the absorbance at 560 nm decreased significantly after Fe doping, indicating that the SOD-like activity was significantly improved by Fe doping.
[0032] Figure 8 The time-dependent oxidation spectrum of •OH generated by Fe-BaTiO3 under ultrasonic irradiation was obtained. Using TMB as an indicator, the generation of •OH in the piezoelectric catalysis process was evaluated by monitoring the change of absorbance at 652 nm over time. It was found that the absorbance increased significantly over time, and the absorbance increased significantly after Fe doping, indicating that Fe-BaTiO3 has a good piezoelectric-enzyme synergistic catalytic effect.
[0033] Example 2
[0034] This embodiment provides a method for preparing barium titanate piezoelectric nanoenzymes based on in-situ mesoporous silica, which includes the following steps:
[0035] (1) Preparation of MSNs:
[0036] Dissolve 1.0 g cetyltrimethyl-p-toluenesulfonium, 0.15 g triethanolamine, and 13 mg 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate in 60 mL of distilled water. Stir at 70 °C for 1.5 h, then add 8 mL of ethyl orthosilicate and continue stirring for 2.5 h. The product is then centrifuged at 8000 rpm / min for 5 min, washed twice with anhydrous ethanol and water, and dispersed in 160 mL of anhydrous ethanol for 20 h to remove the template cetyltrimethyl-p-toluenesulfonium. After centrifugation at 11000 rpm / min for 8 min, the product is washed twice with anhydrous ethanol and dried. The resulting solid is MSNs.
[0037] (2) Preparation of iron-doped barium titanate piezoelectric nanozymes based on in-situ construction of mesoporous silica: 28 mg MSNs were dispersed in anhydrous ethanol, and then a mixed solution containing 2.5 g urea and 0.47 g ammonium chloride (solvents were 5 mL distilled water and 5 mL anhydrous ethanol) was added. After stirring for 2 h, 0.2096 g titanium acetylacetonate was added and stirring was continued for 7 h. Then 0.1665 g barium chloride was added and stirred for 12 h. Finally, 37.8 mg ferric chloride hexahydrate was added and stirring was continued for 12 h. The obtained product was dried in a 60 ℃ oven. The solid product was thoroughly ground in a mortar and then calcined in a muffle furnace at a heating rate of 3 ℃ / min. The temperature was 110 ℃ for 2 h, 200 ℃ for 2 h, 300 ℃ for 2 h, 400 ℃ for 2 h, and the maximum temperature was 500 ℃ for 4 h to obtain the final product Fe-BaTiO3.
[0038] Example 3
[0039] This embodiment provides a method for preparing barium titanate piezoelectric nanoenzymes based on in-situ mesoporous silica, which includes the following steps:
[0040] (1) Preparation of MSNs:
[0041] Dissolve 0.94 g of hexadecyltrimethyl-p-toluenesulfonium, 0.1 g of triethanolamine, and 11 mg of 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate in 65 mL of distilled water. After stirring at 75 °C for 2 h, add 7 mL of ethyl orthosilicate and continue stirring for 1 h. Then, centrifuge the product at 8000 rpm / min for 5 min, wash twice with anhydrous ethanol and water, respectively. Disperse the product in 140 mL of anhydrous ethanol for 22 h to remove the template hexadecyltrimethyl-p-toluenesulfonium. After centrifugation at 11000 rpm / min for 8 min, wash twice with anhydrous ethanol and dry. The obtained solid is MSNs.
[0042] (2) Preparation of iron-doped barium titanate piezoelectric nanozymes based on in-situ construction of mesoporous silica: 28 mg MSNs were dispersed in anhydrous ethanol, and then a mixed solution containing 2.3 g urea and 0.57 g ammonium chloride (solvents were 5 mL distilled water and 5 mL anhydrous ethanol) was added. After stirring for 1 h, 0.2794 g titanium acetylacetonate was added and stirring was continued for 7 h. Then 0.1473 g barium chloride was added and stirred for 12 h. Then 43.2 mg ferric chloride hexahydrate was added and stirring was continued for 12 h. The obtained product was dried in an oven at 60 ℃. The solid product was thoroughly ground in a mortar and finally calcined in a muffle furnace at a heating rate of 3 ℃ / min. The temperature was 110 ℃ for 2 h, 200 ℃ for 2 h, 300 ℃ for 2 h, and the maximum temperature was 400 ℃ for 6 h to obtain the final product Fe-BaTiO3.
[0043] By adopting the above-disclosed technical solution of this invention, the following beneficial effects are obtained:
[0044] This invention discloses a method for in-situ construction of barium titanate piezoelectric nanozymes based on mesoporous silica and their applications. Firstly, the synthesis process is simple and easy to implement, allowing for large-scale preparation, using inexpensive raw materials, and producing nanozymes with uniform particle size distribution and good dispersibility. Secondly, the prepared material exhibits piezoelectric catalytic activity, capable of converting endogenous H2O in tumor cells to •OH and O2 to •O2 under ultrasonic stimulation. - Thirdly, this nanozyme also possesses POD-like and SOD-like activities, and can utilize its SOD-like properties to convert •O2 - The process involves converting the H2O2 to H2O2, alleviating the H2O2 deficiency in the tumor microenvironment. Then, utilizing POD-like activity, the generated H2O2 and endogenous tumor H2O2 are converted into •OH, achieving a piezoelectric catalysis and enzyme cascade reaction to further increase the •OH level, efficiently killing tumor cells and inducing tumor cell death. In conclusion, this nanozyme has considerable market potential.
[0045] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method and application for in-situ construction of barium titanate piezoelectric nanoenzymes based on mesoporous silica, characterized in that, Includes the following steps: S1, Preparation of mesoporous silica (MSNs): Mesoporous silica (MSNs) was prepared using a template method with hexadecyltrimethyl-p-toluenesulfonium, triethanolamine, 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate, and ethyl orthosilicate as raw materials. S2, Preparation of mesoporous silica-confined in-situ iron-doped barium titanate piezoelectric nanozymes: Using MSNs and titanium, barium and iron ions as raw materials, a gradient calcination method was used to prepare mesoporous silica-confined in-situ iron-doped barium titanate piezoelectric nanozymes (denoted as Fe-BaTiO3) with piezoelectric catalytic properties and various enzyme catalytic activities (peroxidase-like and superoxide dismutase-like).
2. The preparation method of barium titanate piezoelectric nanoenzymes based on in-situ construction of mesoporous silica according to claim 1, characterized in that, The MSNs described in step S1 are prepared using a template method. 0.8-1.2 g of hexadecyltrimethyl-p-toluenesulfonium, 0.1-0.2 g of triethanolamine, and 10-15 mg of 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate are dissolved in distilled water and stirred at 80-120°C for 1-3 h. Then, 7-11 mL of ethyl orthosilicate is added, and stirring is continued for another 1-3 h. The product is centrifuged and washed, and then dispersed in anhydrous ethanol for 20-26 h to remove the template hexadecyltrimethyl-p-toluenesulfonium. Finally, the product is centrifuged, washed, and dried to obtain the solid product, which is the MSNs.
3. The preparation method of barium titanate piezoelectric nanoenzymes based on in-situ mesoporous silica construction according to claim 1, characterized in that, Step S2 specifically includes: dispersing 25-45 mg MSNs in anhydrous ethanol, adding a mixed solution containing urea and ammonium chloride and stirring for 2-3 h, adding 0.2-0.3 g titanium acetylacetonate and stirring for 5-8 h, then adding 0.1-0.2 g barium chloride and stirring for 12 h, then adding 40-50 mg ferric chloride hexahydrate and stirring for 10-12 h, drying the obtained product in an oven at 40-60 ℃, grinding the solid product thoroughly in a mortar, and finally calcining it in a muffle furnace at a maximum temperature of 400-500 ℃ for 4-6 h to obtain the final product Fe-BaTiO3.
4. The preparation method of barium titanate piezoelectric nanoenzymes based on in-situ mesoporous silica construction according to claim 1, characterized in that... Add a mixed solution containing urea and ammonium chloride, using 5-10 mL of deionized water and 5-10 mL of anhydrous ethanol as solvents.
5. A barium titanate piezoelectric nanozyme based on mesoporous silica in situ, prepared by any of the preparation methods described in claims 1 to 4.
6. The application of the barium titanate piezoelectric nanozyme based on mesoporous silica in situ as described in claim 5 in targeted tumor catalytic therapy.