Enhanced piezoelectric material for triggering sonodynamic response and preparation method and application thereof
By introducing Cu into UIO-66 material, UIO-66@Cu-SS material was prepared, which solved the problem of insufficient ultrasonic responsiveness and antibacterial properties of piezoelectric materials, achieved stronger POD activity and GSH clearance ability, and improved the effect of sonodynamic therapy.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-30
- Publication Date
- 2026-03-13
AI Technical Summary
Existing piezoelectric materials, especially MOF materials, do not perform well in sonodynamic therapy due to their unsatisfactory piezoelectric effect. Their ultrasonic responsiveness and antibacterial properties need to be improved.
By introducing Cu, UIO-66@Cu-SS material was prepared, which enhanced its piezoelectric properties and ultrasonic responsiveness. Combined with the redox properties of Cu, the POD activity and GSH scavenging ability were improved.
The ultrasound response characteristics of UIO-66 were enhanced, the POD activity was increased by 1.7 times, the Cu ion release efficiency was increased by 120% and 112%, and GSH was effectively cleared, thus improving the therapeutic effect of the antibacterial sonosensitive agent.
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Figure CN121648313A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biotechnology, specifically relating to a piezoelectric material with enhanced triggering acoustic-dynamic response, its preparation method, and its application. Background Technology
[0002] Sonodynamic therapy (SDT) is a method of treating diseases by using nanomaterials to catalyze the production of excess reactive oxygen species (ROS) under the stimulation of external ultrasound. Highly efficient sonosensitive agents are crucial for achieving effective SDT. Piezoelectric sonosensitive agents are piezoelectric nanomaterials that are activated by low-frequency vibration or ultrasound, inducing piezoelectric catalysis to produce potent ROS.
[0003] Currently, piezoelectric materials widely used in antibacterial sound-sensitive agents mainly include perovskite materials such as barium titanate, potassium sodium niobate, and sodium bismuth titanate, as well as two-dimensional nanomaterials such as transition metal sulfide compounds represented by MoS2. These materials possess excellent piezoelectric properties and high mechanical stability, and therefore have attracted increasing attention in the biomedical field.
[0004] Metal-organic frameworks (MOFs) are porous materials composed of metal ions and organic linkers. They possess high specific surface areas and tunable pore sizes, enabling ultra-high drug loading, and thus have attracted significant attention in antibacterial agent delivery systems. Furthermore, using MOF-based nanoplatforms to encapsulate sonosensitive agents and metal ions can construct highly efficient SDT nanosonic sensitizers based on ultrasonically triggered charge separation. Introducing non-centrosymmetric crystal structures during MOF preparation holds promise for constructing piezoelectric MOF materials with both energy conversion and drug loading capabilities, potentially replacing traditional sonosensitive agents to achieve efficient SDT. However, MOF materials exhibiting piezoelectric effects are currently rare. UIO-66, containing Hf, possesses some piezoelectric properties due to the strong polarity of the Hf-O bond, but its piezoelectric effect remains unsatisfactory. Summary of the Invention
[0005] This invention provides an enhanced trigger acoustic-dynamic response piezoelectric material, its preparation method, and its applications. By introducing Cu, the ultrasonic response properties of the piezoelectric material UIO-66 are enhanced, resulting in stronger peroxidase (POD) activity. Furthermore, the introduction of Cu endows the material with GSH scavenging properties, improving its application value in antibacterial SDT treatment.
[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: This invention provides a method for preparing an enhanced triggering acoustic dynamic response piezoelectric material. The method includes: adding hafnium tetrachloride (HfCl4) and aminoterephthalic acid to a mixed solution of DMF and deionized water, transferring the solution to a Teflon liner, stirring continuously until completely dissolved, then heating the reaction and centrifuging to collect the precipitate, washing and drying the precipitate to obtain UIO-66; adding UIO-66 to ethanol containing 3,3'-dithiobis(propionylhydrazine), then adding CuCl2 solution, stirring overnight, centrifuging to collect the precipitate and washing to obtain the enhanced triggering acoustic dynamic response piezoelectric material, denoted as UIO-66@Cu-SS.
[0007] Furthermore, the preparation method is carried out according to the following proportions: the amount of hafnium tetrachloride is 0.15-0.4 g, the amount of aminoterephthalic acid is 0.1-0.3 g, the amount of UIO-66 is 2 mL, and the amount of CuCl2 solution is 0.24 mL.
[0008] Furthermore, the concentration of UIO-66 is 8-12 mg / mL, and the concentration of CuCl2 solution is 65-70 mg / mL. Furthermore, in the mixed solution of DMF and deionized water, 50 mL of DMF and 120-160 μL of deionized water are added.
[0009] Furthermore, the amount of ethanol used is 10 mL, and the concentration of 3,3'-dithiobis(propionylhydrazine) is 0.3-0.6 mg / mL.
[0010] Furthermore, the heating reaction temperature is 110-130 °C, and the reaction time is 22-26 h.
[0011] Furthermore, in the UIO-66 preparation step, washing was performed three times with DMF and ethanol, and drying was performed by placing it in a vacuum drying oven at 60 ℃; in the UIO-66@Cu-SS preparation step, washing was performed three times with ethanol.
[0012] The present invention also provides a piezoelectric material with enhanced acoustic dynamic response prepared by the above-described method for preparing such a piezoelectric material.
[0013] The present invention also provides the application of the above-mentioned enhanced triggering acoustic dynamic response piezoelectric material in the preparation of antibacterial acoustic sensitizers.
[0014] Furthermore, the piezoelectric material with enhanced acoustic-dynamic response is used to catalyze the generation of ROS; when the concentration of the piezoelectric material with enhanced acoustic-dynamic response is 50 μg / mL, the scavenging rate of glutathione (GSH) is above 65%; when the concentration of the piezoelectric material with enhanced acoustic-dynamic response is 120 μg / mL, the scavenging rate of GSH is above 80%.
[0015] In this invention, TMB (Tetramethylbenzidine) was also used as a probe. UIO-66 / UIO-66@Cu-SS was added to an acetate-sodium acetate buffer solution, and hydrogen peroxide (H2O2) was added. No nanomaterials were added to the blank group. After ultrasonic stimulation for 5 minutes, the color changes of the reaction group and the experimental group were observed. The absorbance of the two solutions at 652 nm was measured using a UV-spectrophotometer.
[0016] Preferably, the concentration of H2O2 is 1 M and the volume is 50 μL. The concentration of TMB is 10 mM and the volume is 50 μL.
[0017] Ultrasonic stimulation was applied to each group at the same reaction concentration, and the data were fitted to obtain the results under ultrasonic stimulation. K m and V max Preferably, the intensity of the applied ultrasound is 1 MHz and 1.2 W.
[0018] Compared with the prior art, the present invention has at least the following beneficial effects: This invention provides a piezoelectric material with enhanced triggered acoustodynamic response, its preparation method, and its application. A MOF material of UIO-66 with enhanced piezoelectric properties was prepared. Experimental results show that, under ultrasonic stimulation, UIO-66 promotes the generation of charge carriers (ee) through the piezoelectric effect. - / h + The GSH is separated and generated through a redox cascade reaction, exhibiting sonodynamic response characteristics and POD activity. However, the relevant characteristics of UIO-66 itself are relatively weak. Therefore, UIO-66@Cu-SS prepared by introducing Cu element enhances the sonodynamic response characteristics and has significantly enhanced POD activity (enhanced by at least 1.7 times), promoting the release of ROS. The release efficiency of Cu ions fixed by disulfide bonds is enhanced by 120% and 112% under acidic environment and ultrasonic vibration, respectively, thereby achieving effective removal of GSH. Attached Figure Description
[0019] Figure 1 This is a schematic diagram illustrating the synthesis of UIO-66 and UIO-66@Cu-SS and the principle of triggering the enhanced ultrasonic response.
[0020] Figure 2 Characterization of UIO-66 and UIO-66@Cu-SS; Figure 2 A is the TEM image of UIO-66; Figure 2 B is the TEM image of UIO-66@Cu-SS.
[0021] Figure 3 This is a distribution map of elements in UIO-66@Cu-SS; Figure 3 AE represents the distribution of N, O, S, Cu, and Hf elements in UIO-66@Cu-SS. Figure 3 F represents a comparison of the content of each element.
[0022] Figure 4 The effect of different pH values on the reaction of UIO-66 catalyzing the oxidation of TMB by H2O2.
[0023] Figure 5 This is the Michaelis-Menten equation and its transformed form for different H₂O₂ concentrations, as described in UIO-66. Figure 5 A and B are the Michaelis equation and the LB equation for ultrasound stimulation applied by UIO-66, respectively, and the equation for plotting the double reciprocals.
[0024] Figure 6 This is the Michaelis-Menten equation and its transformation form for different TMB concentrations according to UIO-66. Figure 6 A and B are the Michaelis equation and the LB equation for ultrasound stimulation applied by UIO-66, respectively, and the equation for plotting the double reciprocals.
[0025] Figure 7 This is a comparison of the absorption peak at 652 nm of UIO-66 and UIO-66@Cu-SS after applying ultrasonic stimulation with or without using TMB as a probe.
[0026] Figure 8 This is a comparison of the POD activity of UIO-66-Cu-SS and UIO-66 after ultrasonication.
[0027] Figure 9 This refers to the concentration of Cu ions released under different pH conditions.
[0028] Figure 10 These are the UV absorption spectra of GSH degradation using DTNB with different concentrations of UIO-66-Cu-SS. Detailed Implementation
[0029] The present invention will be further described in detail below with reference to the embodiments. In particular, it should be noted that: unless otherwise specified, the conditions in the following embodiments shall be carried out according to conventional conditions or the conditions recommended by the manufacturer. Unless otherwise specified, the raw materials used in the following embodiments may be derived from commercially available sources.
[0030] Reagents and instruments used in the experiment: Hafnium tetrachloride was purchased from Shanghai Aladdin Reagent Co., Ltd. Amino-terephthalic acid, N,N-dimethylformamide, and copper chloride were purchased from Shanghai Maclean Biological Reagent Co., Ltd. Dimethyl sulfoxide, 30% H2O2, acetic acid, sodium acetate, and anhydrous ethanol were purchased from Sinopharm Group. Glutathione, 3,3′,5,5′,-tetramethylbenzidine, and 5,5′-dithiobis(2-nitrobenzoic acid) were purchased from Innocare Technology Co., Ltd. 3,3′-dithiobis(propionylhydrazine) was purchased from Qingdao Haibo Biotechnology Co., Ltd.
[0031] The morphologies of UIO-66 and UIO-66-Cu-SS were obtained by transmission electron microscopy (JEOL JEM 2100F, Japan). Ultraviolet absorption spectra were measured using a UV-Vis spectrophotometer (Shimadzu UV-1900i, Japan). Cu ion release was measured using a PerkinElmer Nexion 350X (China) inductively coupled plasma mass spectrometer (ICP-MS).
[0032] Example 1: ①The preparation method of the piezoelectric material with enhanced triggering acoustic dynamic response is as follows: 0.275 g hafnium tetrachloride (HfCl4) and 0.155 g aminoterephthalic acid were added to a mixed solution of 50 mL DMF and 140 μL deionized water, transferred to a 100 mL Teflon liner, and stirred continuously until completely dissolved. The mixture was reacted in a reaction vessel in an oven at 120 ℃ for 24 h, and the precipitate was collected by centrifugation. The precipitate was washed three times with DMF and ethanol and dried in a vacuum drying oven at 60 ℃ to obtain UIO-66.
[0033] 2 mL of the prepared UIO-66 (10 mg / mL) was added to 10 mL of ethanol containing 3,3'-dithiobis(propionylhydrazine) (0.5 mg / mL), followed by the addition of 0.24 mL of CuCl2 (68.5 mg / mL) solution. After stirring overnight, the precipitate was collected by centrifugation and washed three times with ethanol to obtain the piezoelectric material with enhanced triggering acoustic-dynamic response, denoted as UIO-66@Cu-SS.
[0034] Figure 1 A schematic diagram illustrating the synthesis of UIO-66 and UIO-66@Cu-SS and the principle of triggering the enhanced ultrasonic response.
[0035] Figure 2 and Figure 3 Characterization of UIO-66 and UIO-66@Cu-SS Figure 2 A is the TEM image of UIO-66; Figure 2B is a TEM image of UIO-66@Cu-SS. It can be seen that UIO-66 and UIO-66@Cu-SS are spherical particles with an average diameter of less than 100 nm. After Cu element is attached, the surface of UIO-66@Cu-SS is slightly rougher than that of UIO-66. Figure 3 This is an elemental distribution diagram of UIO-66@Cu-SS. Figure 3 AE represents the distribution of N, O, S, Cu, and Hf elements in UIO-66@Cu-SS. Figure 3 F represents a comparison of the content of each element. It can be seen that the synthesized material contains Hf, the main element of UIO-66, as well as introduced Cu and S elements.
[0036] ② Investigate the effect of different buffer pH on the reaction of H2O2 oxidation of TMB catalyzed by UIO-66: Prepare HAc-NaAc buffer solutions with pH values of 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, and 6.0 for the enzymatic reaction catalyzed by UIO-66. For a 1 mL reaction system: add 100 μL of 10 mM TMB solution, 50 μL of UIO-66 solution, and 100 μL of 0.5 M hydrogen peroxide. The remaining volume is made up with acetate-sodium acetate buffer. After reacting for 5 min, measure the absorbance at 652 nm.
[0037] Figure 4 The results showed that the absorbance of the reaction system was highest at a pH of approximately 3.5, and then decreased as the pH increased, proving that the optimal pH for the UIO-66-catalyzed enzymatic reaction was 3.5.
[0038] ③ Factors affecting enzymatic reactions and sonodynamic responses—An investigation was conducted on the concentration of H2O2 in the reaction system: H2O2 concentrations of 8 mM, 7 mM, 5 mM, 3 mM, 1 mM, 0.8 mM, 0.5 mM, and 0.3 mM were prepared for enzymatic reactions, with a reaction volume of 1 mL. 100 μL of 10 mM TMB probe and 50 μL of UIO-66 solution were added, and the remaining volume was made up with acetate-sodium acetate buffer at pH 3.5. The absorbance was measured at 652 nm after 5 minutes of reaction. The data were fitted using the Michaelis-Lewis equation and the LB equation, and the Michaelis constant for different substrates was calculated. K m ) and maximum reaction rate ( V max Subsequently, ultrasound stimulation (1 MHz, 1.2 W, 5 min) was applied to each group at the same response concentration, and the data were similarly fitted to obtain the ultrasound stimulation results. K m and V max .
[0039] Figure 5 This refers to the Michaelis equation and its transformation form for H2O2 with different concentrations, as described in UIO-66. Figure 5 A and B are the Michaelis equation and the LB equation for ultrasound stimulation applied by UIO-66, respectively, and the equation for plotting the double reciprocals.
[0040] ④ Factors affecting enzymatic reactions and sonodynamic responses—An investigation into the concentration of TMB in the reaction system: Enzymatic reactions were carried out using TMB concentrations of 2 mM, 1.8 mM, 1.5 mM, 1 mM, 0.8 mM, 0.5 mM, and 0.25 mM, with a total volume of 1 mL. 100 μL of 0.5 M hydrogen peroxide and 50 μL of UIO-66 solution were added, and the remaining volume was made up with acetate-sodium acetate buffer at pH 3.5. The absorbance was measured at 652 nm after 5 minutes of reaction. The data were then fitted using the Michaelis-Lewis equation and the LB equation, and the Michaelis constant for different substrates was calculated. K m ) and maximum reaction rate ( V max Then, ultrasound stimulation was applied to each group at the same reaction concentration, and the data were fitted to obtain the ultrasound stimulation results. K m and V max .
[0041] Figure 6 The Michaelis-Menten equation and its transformation form for UIO-66 with respect to different TMB concentrations are presented. Figure 6 A and B represent the Michaelis equation and the LB equation plotted with double reciprocals for ultrasound stimulation applied to UIO-66.
[0042] Table 1 shows the Michaelis equations obtained for UIO-66 with different H2O2 and TMB concentrations, regardless of whether ultrasound stimulation was applied. K m and V max .
[0043] Table 1
[0044] ⑤ Detection of SDT performance enhancement by UIO-66-Cu-SS: Compare the POD activity of UIO-66@Cu-SS and UIO-66 after the introduction of Cu ions, and the POD activity after ultrasonication, and measure the absorbance at 652 nm.
[0045] Figure 7The results showed that UIO-66 possesses POD enzyme activity, can generate ROS, and exhibits piezoelectric effects. Utilizing the redox properties of Cu, the POD activity of the nanomaterial can be further enhanced. Without ultrasonic stimulation, the POD activity of UIO-66@Cu-SS was 2.37 times higher than that of UIO-66; after ultrasonic stimulation, the POD activity of UIO-66@Cu-SS was 3.23 times higher than that of UIO-66.
[0046] ⑥ Further evidence of the piezoelectric catalytic enhancement effect of Cu on UIO-66: UIO-66 and UIO-66@Cu-SS reaction systems with final concentrations of 10, 20, 40, and 80 μg / mL were prepared, and the absorbance at 652 nm was measured after ultrasonic stimulation was applied.
[0047] Figure 8 The introduction of Cu element demonstrates that it enhances the piezoelectric catalytic activity of UIO-66. When the concentration of both materials is 80 μg / mL, the POD activity of UIO-66@Cu-SS is 1.7 times higher than that of UIO-66.
[0048] ⑦ Cu ion release from UIO-66@Cu-SS material: Buffer solutions with different pH values (5.5 and 7.0) were selected, and ultrasonic and non-ultrasonic groups were set up to detect Cu ion release.
[0049] Figure 9 The results showed that the ability to release Cu ions under ultrasonic stimulation in a neutral environment was 1.12 times that without ultrasonic stimulation. Furthermore, the release ability of Cu ions was also effectively enhanced under acidic conditions, with the concentration of Cu ions released under acidic conditions being 1.2 times that under neutral conditions.
[0050] ⑧ UIO-66@Cu-SS has the effect of scavenging GSH: Prepare a 1050 μL catalytic system of UIO-66@Cu-SS with final concentrations of 10, 20, 50, 80, 100, and 120 μg / mL: Use 0.1 mM DTNB as a probe and add 500 μL; add 1 mM GSH solution and add 100 μL, and make up the remaining volume with PBS.
[0051] Figure 10 This demonstrates that UIO-66@Cu-SS has the ability to scavenge GSH. As shown in the figure, when the concentration of UIO-66@Cu-SS is 50 μg / mL, the GSH scavenging rate can reach 65%, and when the concentration reaches 120 μg / mL, it can scavenge more than 80% of GSH. The above description is merely an exemplary embodiment of this disclosure, but the scope of protection of this disclosure is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this disclosure should be included within the scope of protection of this disclosure. Therefore, the scope of protection of this disclosure should be determined by the scope of the claims.
Claims
1. A method for preparing a piezoelectric material with enhanced triggered acoustic-dynamic response, characterized in that, The preparation method includes: Hafnium tetrachloride and aminoterephthalic acid were added to a mixed solution of DMF and deionized water, transferred to a Teflon liner, and stirred continuously until completely dissolved. After heating and reacting, the precipitate was collected by centrifugation. The precipitate was washed and dried to obtain UIO-66. UIO-66 was added to ethanol containing 3,3'-dithiobis(propionylhydrazine), and then CuCl2 solution was added. The mixture was stirred overnight, and the precipitate was collected by centrifugation and washed to obtain the piezoelectric material with enhanced triggering acoustic-dynamic response, denoted as UIO-66@Cu-SS.
2. The method for preparing the piezoelectric material with enhanced triggered acoustic-dynamic response according to claim 1, characterized in that, The preparation method is carried out according to the following proportions: the amount of hafnium tetrachloride is 0.15-0.4 g, the amount of aminoterephthalic acid is 0.1-0.3 g, the amount of UIO-66 is 2 mL, and the amount of CuCl2 solution is 0.24 mL.
3. The method for preparing the piezoelectric material with enhanced triggered acoustic-dynamic response according to claim 2, characterized in that, The concentration of UIO-66 is 8-12 mg / mL, and the concentration of CuCl2 solution is 65-70 mg / mL.
4. The method for preparing the piezoelectric material with enhanced triggered acoustic-dynamic response according to claim 2, characterized in that, In a mixed solution of DMF and deionized water, add 50 mL of DMF and 120-160 μL of deionized water.
5. The method for preparing the piezoelectric material with enhanced triggered acoustic-dynamic response according to claim 2, characterized in that, The amount of ethanol used is 10 mL, and the concentration of 3,3'-dithiobis(propionylhydrazine) is 0.3-0.6 mg / mL.
6. The method for preparing the piezoelectric material with enhanced triggered acoustic-dynamic response according to claim 1, characterized in that, The heating reaction is carried out at a temperature of 110-130 °C for a time of 22-26 h.
7. The method for preparing the piezoelectric material with enhanced triggered acoustic-dynamic response according to claim 1, characterized in that, In the preparation of UIO-66, washing was performed three times with DMF and ethanol, and drying was performed by placing it in a vacuum drying oven at 60 ℃. In the preparation of UIO-66@Cu-SS, the washing process involved washing three times with ethanol.
8. A piezoelectric material with enhanced triggering acoustic dynamic response prepared by a method for preparing a piezoelectric material with enhanced triggering acoustic dynamic response according to any one of claims 1 to 7.
9. The application of the piezoelectric material with enhanced triggering acoustic dynamic response as described in claim 8 in the preparation of an antibacterial acoustic sensitizer.
10. The application according to claim 9, characterized in that, The piezoelectric material with enhanced triggering acoustic-dynamic response is used to catalyze the generation of ROS; When the concentration of the piezoelectric material with enhanced acoustic-dynamic response is 50 μg / mL, the GSH removal rate is above 65%; when the concentration of the piezoelectric material with enhanced acoustic-dynamic response is 120 μg / mL, the GSH removal rate is above 80%.