Preparation method and application of lithium-doped SrTiO3 nanometer piezoelectric material

Abstract

The invention discloses a preparation method and application of a lithium-doped SrTiO3 nanometer piezoelectric material, and the preparation method comprises the following steps: S10: mixing TiO2 powder and a lithium foil block, grinding the mixture until the mixture is spontaneously combusted, and taking the obtained black combustion product as a precursor; and S20, taking the precursor and a strontium source as reaction raw materials, and synthesizing the lithium-doped SrTiO3 nano piezoelectric material by adopting a hydrothermal synthesis method. The prepared lithium-doped SrTiO3 nanometer piezoelectric material can be used as a sound-sensitive agent in sonodynamic therapy. According to the lithium-doped strontium titanate synthesized by the method disclosed by the invention, active oxygen generated under the ultrasonic action can effectively remove tumor cells and tissues; the released lithium element can significantly promote infiltration of CD8 + T cells into a tumor microenvironment, and synergistic interaction of piezoelectric catalytic therapy and immunotherapy is realized, so that the anti-tumor curative effect is further improved.

Description

Technical Field

[0001] This application relates to the field of medical materials technology, specifically to a method for preparing lithium-doped SrTiO3 nanopiezoelectric materials and their applications. Background Technology

[0002] Sonodynamic therapy (SDT) is an emerging cancer treatment strategy. Its core principle is to utilize ultrasound to activate a piezoelectric sonosensitive agent, generating cytotoxic reactive oxygen species (ROS) in situ within the tumor, thereby efficiently eliminating tumor cells. Strontium titanate (SrTiO3), as a perovskite material, exhibits significant piezoelectric catalytic activity. Furthermore, strontium possesses unique biological effects that inhibit tumor growth and metastasis, making SrTiO3 a highly promising candidate sonosensitive agent for sonodynamic therapy. However, the low carrier density and rapid carrier recombination of SrTiO3 limit its ROS generation capacity. These issues need to be addressed if SrTiO3 is to be used as a sonosensitive agent catalyst. Summary of the Invention

[0003] The purpose of this application is to provide a method for preparing lithium-doped SrTiO3 nanopiezoelectric materials and their applications.

[0004] This application provides a method for preparing lithium-doped SrTiO3 nanopiezoelectric materials, including the following steps: S10: Mix TiO2 powder and lithium foil blocks, grind the mixture until it spontaneously combusts, and use the resulting black combustion product as a precursor; S20: Lithium-doped SrTiO3 nanopiezoelectric materials were synthesized using a hydrothermal synthesis method with precursors and strontium sources as reaction raw materials.

[0005] In step S10, the main component of the obtained precursor is lithium titanate, either stoichiometric or non-stoichiometric, and its chemical formula can be represented as Li. x TiO2, where the x value is determined based on the molar ratio of lithium to TiO2.

[0006] Optionally, in step S10, TiO2 powder and lithium foil are taken at a lithium to TiO2 molar ratio of 0.5 to 2:1.

[0007] When the molar ratio of lithium to TiO2 is 0.5~2:1, the value of x is 0.5~2.

[0008] When the molar ratio of lithium to TiO2 is 0.5 to 1:1, the resulting lithium-doped SrTiO3 piezoelectric nanomaterial exhibits improved piezoelectric catalytic performance compared to strontium titanate. When the molar ratio of lithium to TiO2 is 1 to 2:1, the resulting lithium-doped SrTiO3 piezoelectric nanomaterial shows significantly improved piezoelectric catalytic performance compared to strontium titanate.

[0009] In step S10, lithium reduction of TiO2 is achieved by solid-state grinding. In order to promote efficient reaction, in some embodiments, the lithium foil block is a square block with a side length of 2mm to 5mm.

[0010] Optionally, the hydrothermal synthesis of lithium-doped SrTiO3 nanopiezoelectric materials further includes: S21: Add deionized water to the reactor and adjust the pH to >13; S22: Add the precursor and stir until the precursor is completely dissolved; S23: Add strontium source and stir for 1-2 hours, then seal the reactor at 160-220°C and react for 12-36 hours.

[0011] In a strongly alkaline environment, titanium in the precursor reacts with OH-. - They combine to form soluble titanium oxide complexes, thereby dissolving the water-insoluble precursors.

[0012] The purpose of stirring for 1 to 2 hours in step S23 is to ensure that the precursor and strontium source are fully mixed.

[0013] Optionally, in step S21, the pH is adjusted to >13 by adding potassium hydroxide and / or sodium hydroxide.

[0014] Optionally, the strontium source is one or more of strontium hydroxide octahydrate (Sr(OH)2·8H2O), strontium chloride (SrCl2), and strontium nitrate (Sr(NO3)2).

[0015] Optionally, in step S20, to ensure complete reaction, the molar ratio of Ti in the precursor to Sr in the strontium source is 1:2~5.

[0016] In step S20, the molar number of Ti and Sr elements is determined based on the molar ratio of Ti in the precursor to Sr in the strontium source; the molar number of Ti and Sr elements is determined based on the chemical formula of the precursor, Li. x The mass of the precursor is calculated based on the number of moles of TiO2 and Ti; the mass of the strontium source is determined based on the number of moles of Sr.

[0017] Optionally, step S10 may also include washing the black combustion products.

[0018] Optionally, step S20 further includes collecting the reaction precipitate and washing the reaction precipitate.

[0019] On the other hand, this application provides the application of the lithium-doped SrTiO3 nanopiezoelectric material prepared by the above preparation method as a sonosensitive agent for sonodynamic therapy.

[0020] Compared with the prior art, this application has the following advantages and beneficial effects: This application employs a solid-state grinding method to prepare the precursor Li. x TiO2 was used to synthesize lithium-doped strontium titanate modified with oxygen vacancy defects via a hydrothermal synthesis method. Lithium doping not only increases the carrier concentration of the piezoelectric material but also introduces oxygen vacancy defects, with both synergistically enhancing the piezoelectric catalytic performance. At the crystal structure level, the introduction of lithium ions increases the asymmetry of the crystal structure, promoting the transformation of strontium titanate from a centrosymmetric cubic phase to a piezoelectric tetragonal phase, thereby significantly promoting the generation of a large amount of active oxygen.

[0021] The lithium-doped strontium titanate synthesized in this application exhibits strong reactive oxygen species (ROS) generation capacity under ultrasound irradiation. In vitro cell experiments and in vivo homologous tumor models have jointly confirmed that this lithium-doped strontium titanate can effectively kill tumor cells under ultrasound irradiation. Simultaneously, it demonstrates excellent biocompatibility in the physiological environment. Furthermore, lithium doping can produce a dual synergistic effect through the coupling of piezoelectric catalysis and immune activation. It can directly eliminate tumor cells through the piezoelectric catalytic mechanism and enhance the anti-tumor efficacy of the system by utilizing the activated immune response. This multimodal synergistic therapeutic strategy opens up new avenues for sonodynamic therapy.

[0022] Please see Figure 24 This study demonstrates the mechanism by which lithium-doped SrTiO3 nanopiezoelectric materials enhance antitumor therapy. Under ultrasound, the generated reactive oxygen species can effectively eliminate tumor cells and tissues; the released lithium can significantly promote CD8+. + T cells infiltrate the tumor microenvironment, achieving a synergistic effect between piezoelectric catalytic therapy and immunotherapy, and further enhancing the anti-tumor efficacy. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0024] Figure 1 Photographs of 0.5LTO, 1.0LTO, and 1.5LTO precursor powders are shown. Figure 2 XRD images of pristine titanium dioxide and 0.5LTO, 1.0LTO, 1.5LTO and 2.0LTO precursors are shown; Figure 3 The XPS full spectra of TiO2 and 1.5LTO precursors are shown; Figure 4The O 1s peak fitting results for TiO2 and 1.5LTO precursors are shown; Figure 5 XRD images of STO and 1.5 LSTO are shown; Figure 6 The O 1s peak fitting results for STO are shown; Figure 7 The results of Ti 2p peak fitting for STO are shown; Figure 8 The results of O 1s peak fitting for 1.5LSTO are shown; Figure 9 The results of Ti 2p peak fitting for 1.5 LSTO are shown; Figure 10 The EPR spectra of STO and 1.5 LSTO are shown; Figure 11 A TEM image of STO is shown; Figure 12 A TEM image of 1.5 LSTO is shown; Figure 13 The HRTEM diagram of STO is shown; Figure 14 The HRTEM plot of 1.5 LSTO is shown; Figure 15 The transient response of STO and 1.5LSTO to piezoelectric current is shown; Figure 16 The performance of STO and 1.5 LSTO in catalytic degradation of RhB is shown; Figure 17 Fluorescence microscopy images of live / dead cells of 3T3 cells stained with Calcein AM / PI to capture STO material are shown, scale bar 50 μm; Figure 18 Fluorescence microscopy images of live / dead cells stained with Calcein AM / PI on 3T3 cells captured from 1.5 LSTO material are shown, scale bar 50 μm; Figure 19 Fluorescence microscopy images of live / dead cells stained with Calcein AM / PI on STO-captured CT26 cells are shown, scale bar 50 μm; Figure 20 Fluorescence microscopy images of live / dead cells stained with Calcein AM / PI on CT26 cells captured from 1.5 LSTO material are shown, scale bar 50 μm; Figure 21 The survival rates of CT26 cells under different treatments are shown. Figure 22The average tumor growth curves of mice under different treatment regimens are shown. Figure 23 The images show the morphological photographs of tumors in each group 14 days after treatment. Figure 24 The therapeutic mechanism of the lithium-doped SrTiO3 nanopiezoelectric material of this application is illustrated. Detailed Implementation

[0025] The technical solutions and effects of this application will be clearly and completely described below with reference to specific embodiments, examples, and comparative examples. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application. Example 1

[0026] This embodiment describes the preparation of a precursor. Lithium-reduced TiO2 precursors with different lithium doping levels are prepared using a solid-state grinding method in an argon-protected glove box. The steps include: S11: Weigh 2g of TiO2 powder, cut lithium foil into pieces and mix it with TiO2 powder according to the preset molar ratio; grind the mixture in an agate mortar with a pestle, and mix it regularly with a scraper until a uniform mixture is formed; the mixture spontaneously combusts during the grinding process, and collect the resulting black combustion product; S12: The combustion products were washed with 0.2 mol / L acetic acid solution to remove unreacted metallic lithium; then thoroughly rinsed with deionized water and anhydrous ethanol, and dried to obtain nanoscale black precursor powder.

[0027] In this embodiment, four precursor powders with Li:TiO2 molar ratios of 0.5:1, 1:1, 1.5:1, and 2:1 were prepared and labeled as 0.5LTO, 1.0LTO, 1.5LTO, and 2.0LTO, respectively.

[0028] Please see Figure 1 The image shown is a photograph of 0.5LTO, 1.0LTO, and 1.5LTO precursor powders. From... Figure 1 As can be seen, the color of the precursor powder gradually deepens with increasing lithium doping concentration. The inventors speculate that this phenomenon may be due to lithium metal acting as a strong reducing agent, reacting with lattice oxygen to directly reduce titanium dioxide, thereby leading to enhanced visible light absorption.

[0029] Please see Figure 2 The image shows XRD images of TiO2 and its precursors of 0.5LTO, 1.0LTO, 1.5LTO, and 2.0LTO. From... Figure 2The changes in the titanium dioxide crystal structure during lithium reduction are evident: the original TiO2 is in the anatase phase, and after lithium reduction, in addition to the inherent titanium dioxide phase, various lithium titanate phases also appear. Notably, the content of the rock-salt LiTiO2 phase increases with the increase of the lithium molar ratio. When the lithium-titanium molar ratio reaches 1:1, the rock-salt LiTiO2 phase becomes the dominant phase; when the lithium-titanium molar ratio increases to 1.5:1, the anatase titanium dioxide phase almost completely transforms into the rock-salt LiTiO2 phase.

[0030] This phase transition may originate from the solid-state diffusion of lithium ions within the titanium dioxide lattice during the grinding process, prompting lithium ion insertion into the lattice and thus initiating the phase transition. During lithium ion insertion, Li... + and Ti 3+ Both lithium and titanium coexist within the titanium dioxide crystal structure. When the lithium-to-titanium ratio continues to increase to 2:1, although no new phase composition appears, the diffraction peak intensity of LiTiO2 decreases, while the full width at half maximum (FWHM) increases. This phenomenon may be due to the excess metallic lithium participating in the reaction, disrupting the crystal structure and leading to numerous structural defects. This indicates that when the lithium-to-titanium ratio is 1.5, the lithium-ion intercalation capacity is relatively suitable.

[0031] Please see Figure 3 The image shows the XPS full spectrum of TiO2 and 1.5LTO precursors. Figure 3 The XPS spectrum of 1.5LTO clearly shows the presence of lithium, which further proves that lithium ions are gradually inserted into the lattice to form LiTiO2 during the grinding process.

[0032] Please see Figure 4 The figure shows the O 1s peak fitting results for TiO2 and 1.5LTO precursors. From... Figure 4 It can be seen that the characteristic peaks at 529.79 eV and 531.67 eV in the high-resolution O 1s spectrum correspond to lattice oxygen and oxygen vacancies, respectively. Clearly, the 1.5LTO precursor obtained by lithium reduction contains a large number of oxygen vacancies, indicating that active lithium can effectively remove lattice oxygen to generate a large number of oxygen vacancies. These oxygen vacancies can increase the carrier concentration of the material, thereby improving its catalytic performance. Example 2

[0033] This embodiment describes the synthesis of lithium-doped strontium titanate using a hydrothermal synthesis method, including the following steps: S21: Add 37.5 mL of deionized water to the polytetrafluoroethylene reactor, then add 6 g of sodium hydroxide (NaOH) and stir until completely dissolved; then add 0.75 g of precursor powder (1.5 L TO) to the alkaline solution and stir for 10 minutes; then add 4.97 g of strontium hydroxide octahydrate (Sr(OH)2·8H2O) and stir vigorously for 1 hour to ensure uniform mixing; place the sealed reactor in an oven and maintain at 210 °C for 24 hours. S22: Collect the reaction precipitate, wash repeatedly with 1 mol / L HNO3 to remove residual hydroxide ions and soluble substances, and finally rinse thoroughly with deionized water and anhydrous ethanol to obtain lithium-doped strontium titanate, labeled as 1.5LSTO.

[0034] To compare the performance changes of strontium titanate before and after lithium doping, a control sample of strontium titanate, labeled STO, was synthesized using TiO2 as a precursor under the same process conditions.

[0035] Please see Figure 5 The image shows the XRD patterns of STO and 1.5LSTO, which reveal that both STO and 1.5LSTO exhibit high crystallinity. Compared to STO, 1.5LSTO shows lower diffraction peak intensities; this difference in intensity can be attributed to the Li content during synthesis. + Lattice distortion caused by entering the TiO2 crystal structure. Li + Its radius is 0.76 Å, significantly larger than that of Ti. 4+ Radius (0.61 Å). Li + Replace Ti 4+ This leads to lattice distortion, thereby altering the crystal's structure factor. Furthermore, oxygen vacancies introduced into the crystal during lithium reduction also affect crystallinity, ultimately directly influencing the intensity of XRD diffraction peaks by changing the structure factor.

[0036] Please see Figures 6-7 The figure shows the O 1s peak fitting results and the Ti 2p peak fitting results for STO; please refer to [link / reference]. Figures 8-9 The figure shows the O 1s peak fitting results and the Ti 2p peak fitting results for 1.5LSTO. From... Figures 6-9 It can be seen that STO has a set of split peaks, Ti 2p 3 / 2 Peak (458.25 eV) and Ti 2p 1 / 2 The peak (463.96 eV) all exhibited tetravalent titanium (Ti). 4+ The 1.5 LSTO assay showed two pairs of split peaks, with 458.28 eV and 457.76 eV corresponding to Ti values, respectively. 4+ 2p 3 / 2 With Ti 3+ 2p 3 / 2 The peak, at 463.98 eV, corresponds to Ti. 4+ 2p 1 / 2 The peak, 463.12 eV, corresponds to Ti. 3+ 2p 1 / 2 peak.

[0037] Ti 3+Higher Ti content corresponds to stronger intermediate bandgap energy levels. These intermediate levels can effectively narrow the material's bandgap and, as electron trapping centers, suppress electron-hole recombination, thereby significantly extending carrier lifetime and enhancing surface reactivity. Therefore, materials with higher Ti content exhibit superior performance. 3+ Samples with a 1.5 LSTO content may exhibit superior catalytic performance.

[0038] The characteristic peaks of the O 1s spectrum of 1.5LSTO at 529.48 eV, 531.21 eV, and 532.35 eV correspond to lattice oxygen, oxygen vacancies, and surface adsorbed oxygen, respectively. Peak fitting results for 1.5LSTO show a clear characteristic peak of oxygen vacancies, while this feature is not observed in STO. The 1.5LSTO prepared by lithium reduction contains a large number of oxygen vacancies, indicating that lithium can generate oxygen vacancies by consuming lattice oxygen. The introduction of oxygen vacancies increases the carrier concentration of the material, thereby enhancing its catalytic performance.

[0039] Please see Figure 10 The image shows the EPR spectra of STO and 1.5LSTO. Electron paramagnetic resonance (EPR) testing further confirms the presence of oxygen vacancies. The EPR signal in the g range of 1.960–1.990 originates from Ti. 3+ Site. An EPR peak at g=1.961 was observed in the EPR spectrum of 1.5 LSTO, which can be attributed to the intrinsically introduced Ti during the synthesis process. 3+ Furthermore, compared to STO, 1.5LSTO exhibits an enhanced EPR signal at g=2.003, which can be identified as electrons trapped in oxygen vacancies, confirming the presence of oxygen vacancies and the increased oxygen vacancy concentration due to lithium doping.

[0040] Based on the above series of phase characterization results, the evolution path of the crystal structure during the synthesis of lithium-doped strontium titanate in this application can be clearly identified. A series of characterizations confirm that the crystal structure undergoes an evolution process from anatase TiO2 to rock salt LiTiO2, and finally forms perovskite Li-SrTiO3.

[0041] Please see Figures 11-12 The image shows TEM images of STO and 1.5LSTO. As can be seen, the particle size distribution of both STO and 1.5LSTO ranges from 20 to 80 nanometers. In terms of morphology, STO particles mainly exhibit a regular cubic shape, while 1.5LSTO particles show a more irregular morphology, indicating that lithium doping induces a significant morphological transformation. This effect stems from the use of solid-state grinding to prepare the lithium-doped precursor, which significantly alters the crystal surface energy during SrTiO3 formation. Simultaneously, oxygen vacancies generated during the reaction induce edge defect formation, ultimately affecting the crystal growth process.

[0042] Further analysis using high-resolution transmission electron microscopy (HRTEM) combined with Fast Fourier Transform (FFT) and Inverse Fast Fourier Transform (IFFT) was employed to clarify the crystal structures of STO and 1.5LSTO. Regions were selected from the HRTEM images of STO and 1.5LSTO, and FFT and IFFT images of these selected regions were obtained. (See attached image). Figures 13-14 As shown in the figure, STO nanocrystals are single-crystal structures with clear lattice fringes and a measured spacing of 0.273 nm, corresponding to the (110) crystal plane; the measured spacing of 1.5LSTO is 0.280 nm, slightly larger than that of STO, but also corresponding to the (110) crystal plane. Both STO and 1.5LSTO exhibit isotropic crystal plane characteristics. These findings indicate that the crystallographic spacing of the material increases after elemental doping. Oxygen vacancies and Li + The coexistence of these vacancies can drive the local structure to a tetragonal phase transition. More importantly, oxygen vacancies themselves induce significant expansion of the surrounding lattice. The local lattice expansion caused by vacancies, together with significant c-axis elongation, dominates the process, ultimately leading to an increase in the interplanar spacing measured along a specific crystallographic orientation.

[0043] The catalytic activity of piezoelectric materials is closely related to the efficient migration of electron-hole pairs induced by the piezoelectric effect. The mechanism by which lithium-doped strontium titanate generates free radicals and releases lithium ions in an aqueous system under the influence of external ultrasound is as follows: nanoparticles are polarized under ultrasound, reacting with water to generate •OH and •O2. - It contains reactive oxygen species and releases lithium ions simultaneously. The lithium ion release concentration in 1.5 LSTO is approximately 10.02 mg / L.

[0044] Please see Figure 15 The transient response of STO and 1.5LSTO to piezoelectric current is shown in the figure. It can be seen from the figure that STO has a relatively low piezoelectric current density, while the transient response of 1.5LSTO is significantly enhanced. This enhancement can be attributed to the increased asymmetry of the crystal structure due to lithium-ion doping, thereby improving the piezoelectric properties of the material. Furthermore, oxygen vacancies can trap holes, reducing electron-hole recombination and thus enhancing the electron-hole pair separation efficiency, further increasing the current density.

[0045] Furthermore, the ability of STO and 1.5 LSTO to catalyze the degradation of RhB under ultrasonic conditions was evaluated, see [reference needed]. Figure 16As shown, C0 and C represent the initial and real-time concentrations of the RhB solution, respectively. To minimize the influence of temperature and light on dye degradation, the experiment was conducted in a dark room at room temperature. The results showed that both STO and 1.5 LSTO effectively degraded RhB after 120 minutes of ultrasonic excitation. However, 1.5 LSTO exhibited superior degradation performance, achieving a degradation rate of over 90% in just 80 minutes, while STO required 120 minutes to achieve the same effect. Example 3

[0046] This example is an embodiment for evaluating the in vitro antitumor effects of STO and 1.5LSTO.

[0047] First, the catalytic therapeutic effect of 1.5 LSTO was verified at the cellular level. The material's toxicity was assessed using the standard MTT assay. NIH-3T3 cells (mouse fibroblast cell line) and CT26.WT cells (mouse colon cancer cell line) were co-cultured with the material for 24 hours. Even at concentrations as high as 80 mg / L... -1 Neither STO nor 1.5 LSTO showed significant cytotoxicity. At the same material concentration, CT26 cells exhibited lower viability than 3T3 cells, which may be due to the antitumor effect of lithium ions reducing tumor cell activity. To further assess cytotoxicity, the treated groups were stained with calcein-AM (green, live cells) and propidium iodide (red, dead cells). Fluorescence microscopy images (see...) Figures 17-20 The study showed significant cytotoxicity at higher nanoparticle concentrations, manifested as enhanced red fluorescence. At a concentration of 80 mg / L, the fluorescence signal was predominantly green with very little red staining, indicating that the cell layer remained healthy and viable; therefore, this concentration was used in subsequent cell and animal experiments.

[0048] The impact of these materials on cancer cell survival was evaluated using CT26 cells as a tumor model. Figure 21 As shown, cell survival rate did not decrease significantly when co-cultured with the material alone, indicating that the material itself does not produce cytotoxicity to tumor cells. However, when combined with ultrasound treatment, tumor cell survival rate decreased significantly: at 80 mg / L... -1 At the specified concentrations, the cell survival rate in the STO+US group was 52%, while the cell survival rate in the 1.5L STO+US group significantly decreased to below 17%, exhibiting the most significant anti-tumor effect. The toxic effects of the material on tumor cells were highly consistent with the results of the piezoelectric catalytic dye degradation experiment, confirming that the generation of ROS by the piezoelectric material under ultrasonic stimulation is one of the key factors in achieving the anti-tumor effect. Comparative analysis revealed that ultrasonic treatment alone showed only a slight therapeutic effect on tumor cells.

[0049] The above results indicate that the prepared material itself has weak cytotoxicity, but it can produce a significant cytotoxic effect on tumor cells under ultrasonic stimulation. This phenomenon suggests that the therapeutic effect of the material on tumor cells is directly related to its piezoelectric catalytic activity under ultrasonic irradiation. Example 4

[0050] This example is an embodiment for evaluating the in vivo antitumor effects of STO and 1.5LSTO.

[0051] A tumor-bearing mouse model was established by subcutaneously inoculating CT26 tumor cells into BALB / c mice. On the first day of the experiment, all animals in the experimental groups were injected with nanoparticles via the tail vein. For the ultrasound therapy group, the tumor area was irradiated with ultrasound on days 1, 3, 5, and 7 after injection to activate the piezoelectric catalytic effect. Notably, no significant weight fluctuations were observed in any of the treatment groups throughout the experiment, preliminarily confirming the biocompatibility of this treatment strategy.

[0052] The antitumor effects of different experimental groups were evaluated by analyzing tumor volume changes: the 1.5 LSTO+US group had the smallest tumor volume, indicating the most significant tumor growth inhibition effect; both the STO+US group and the 1.5 LSTO group showed moderate therapeutic effects, with a slowdown in tumor growth rate; in contrast, the tumor volume in the PC group and the STO group continued to increase throughout the treatment period, showing no tumor inhibition effect. Figure 22 As shown. Tumor samples collected at the experimental endpoint (day 14 post-treatment) during euthanasia showed that the 1.5 LSTO+US group exhibited the most significant tumor volume reduction among all experimental groups, and macroscopic assessment confirmed extremely small residual tumor volume. Figure 23 As shown.

[0053] Immunohistochemical staining analysis of tumor tissue sections showed that Ki-67, a marker of invasive cell proliferation, was expressed at the highest level in the PC group. Compared with the PC group, significant inhibition of Ki-67 expression was observed in all experimental treatment groups, with the lowest Ki-67 expression level observed in the 1.5LSTO+US group, indicating its most significant tumor-suppressive effect. Interestingly, the 1.5LSTO group (without ultrasound) still showed better tumor-suppressive effects than the STO and STO+US groups, suggesting that lithium ions in the material may exert an endogenous anti-tumor effect through an ultrasound-independent mechanism.

[0054] TUNEL staining revealed differences in apoptosis responses among the groups: the tumor cell apoptosis rate was highest in the 1.5 LSTO+US group, approximately 3.81 times that of the 1.5 LSTO group alone, and significantly higher than that of the STO+US group. Notably, a comparison between the 1.5 LSTO and undoped STO groups showed that lithium doping endowed strontium titanate with endogenous antitumor activity.

[0055] Immunohistochemical analysis showed that, after specific immunostaining, CD8+ was present in tumor tissue sections. + T cells exhibited a characteristic brownish-yellow staining. Notably, the lithium-doped material treatment group showed a large number of CD8+ cells in the tumor microenvironment. + T cell infiltration, and ultrasound stimulation can enhance CD8. + T cell chemotaxis toward the tumor site. As a key indicator for assessing antitumor immune responses, this infiltration level demonstrates that lithium doping combined with ultrasound significantly promotes CD8 cell chemotaxis. + T cell recruitment to the tumor site.

[0056] All the data above collectively demonstrate that 1.5 LSTO exhibits significantly enhanced piezoelectric catalytic performance compared to undoped STO, thereby increasing ROS generation efficiency under ultrasonic conditions. This optimized ROS generation capability can further improve the antitumor efficacy of the material. Notably, lithium doping endows 1.5 LSTO with intrinsic antitumor properties, and its therapeutic effect is significantly superior to that of the original STO material. It is also noteworthy that the incorporation of lithium achieves a dual synergistic effect of coupled piezoelectric catalysis and immune activation: it facilitates the direct killing of tumor cells through piezoelectric catalysis and enhances the system's antitumor capacity through activated immune responses, thus promoting the effective integration of piezoelectric catalytic therapy and tumor immunotherapy. In conclusion, the combined treatment of 1.5 LSTO and US can effectively inhibit tumor cell growth and promote CD8 activation. + T cells are recruited to the tumor site, thereby enhancing tumor cell apoptosis.

[0057] The various embodiments of the present invention have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or improvement of the technology in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.

Claims

1. A method for preparing a lithium-doped SrTiO3 nano-piezoelectric material, characterized in that, The method comprises the steps of: S10: mixing TiO2 powder and lithium foil blocks, grinding the mixture until the mixture is self-ignited, and taking the black combustion product as a precursor; S20: using a hydrothermal synthesis method to synthesize lithium-doped SrTiO3 nano piezoelectric material by taking the precursor and a strontium source as reaction raw materials.

2. The method of claim 1, wherein: In step S10, the TiO2 powder and lithium foil blocks are taken in a molar ratio of lithium to TiO2 of 0.5-2:

1.

3. The method of claim 1, wherein: The lithium foil blocks are square blocks with a side length of 2-5 mm.

4. The method of claim 1, wherein: The hydrothermal synthesis method for synthesizing lithium-doped SrTiO3 nano piezoelectric material further comprises: S21: adding deionized water to a reaction kettle and adjusting the pH to be greater than 13; S22: adding the precursor and stirring to completely dissolve the precursor; S23: adding the strontium source and stirring for 1-2 h, then sealing the reaction kettle at a temperature of 160-220 ℃ and reacting for 12-36 h.

5. The method of claim 1 or 4, wherein: In step S21, the pH is adjusted to be greater than 13 by adding potassium hydroxide and / or sodium hydroxide.

6. The method of claim 1, wherein: The strontium source is one or more of strontium hydroxide octahydrate, strontium chloride, and strontium nitrate.

7. The method of claim 1 or 4, wherein: The molar ratio of Ti in the precursor to Sr in the strontium source is 1:2-5.

8. The method of claim 1, wherein: Step S10 further comprises washing the black combustion product.

9. The method of claim 1, wherein: Step S20 further comprises collecting the reaction precipitate and washing the reaction precipitate.

10. The use of the lithium-doped SrTiO3 nano piezoelectric material prepared by the method of any one of claims 1-9 as a sonodynamic therapy sonosensitizer.

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