Copper / oxygen-deficient barium titanate piezoelectric heterojunction nanoparticles, preparation and application thereof

Abstract

The present application relates to the technical field of biomedical materials, and particularly relates to copper / oxygen defect barium titanate piezoelectric heterojunction nanoparticles and preparation and application thereof.The copper / oxygen defect barium titanate piezoelectric heterojunction nanoparticles of the present application take tetragonal phase barium titanate as a core, an oxygen defect amorphous layer as a shell, and a heterojunction is formed by depositing a non-valent copper nanocluster (Cu-Cu + ) on the surface of the shell layer; the copper / oxygen defect barium titanate piezoelectric heterojunction nanoparticles have an "electronic lever" effect, can be used for wound repair treatment by precisely regulating the "antibacterial-promoting repair" time sequence treatment under the action of ultrasound, and can rapidly and massively produce ROS and release copper ions under the action of ultrasound activation, so as to induce copper death of bacteria and achieve efficient antibacterial effect. Then, in the tissue repair stage, the ultrasound is turned off, and the intrinsic electric field of the heterojunction and the release of a small amount of copper ions are utilized to promote granulation tissue regeneration, collagen deposition, epithelial regeneration and angiogenesis, so as to synergistically accelerate tissue repair.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticle and its preparation and application. Background Technology

[0002] Wound infection is a key factor hindering the healing process, often leading to delayed tissue repair or even healing failure. For a long time, antibiotic therapy has been the main clinical method for controlling wound infection, but the rapid development of bacterial resistance and the formation of biofilms have increasingly limited its effectiveness. Sonodynamic therapy (SDT), as a non-invasive antibacterial strategy, has attracted much attention due to its advantages such as minimal tissue damage, strong penetration, and low likelihood of inducing drug resistance. Piezoelectric nanomaterials, under ultrasonic excitation, can not only generate local piezoelectric potentials but also induce electron-hole pair separation to catalyze the generation of reactive oxygen species (ROS), and are widely used as sound sensitizers. Specifically, electrons and holes react with O2 and H2O, respectively, to catalyze the generation of •O2. — and •OH.

[0003] However, the rapid recombination of electron-hole pairs induced by piezoelectric materials after separation (femtoseconds to nanoseconds) severely limits their catalytic efficiency due to the kinetic mismatch between this and the relatively slow chemical reactions (milliseconds to seconds). To overcome this bottleneck, introducing metal / semiconductor (Schottky) heterostructures is a feasible approach. This structure not only effectively reduces the material band gap but also allows electrons to be captured by the semiconductor conduction band (CB) across the Schottky barrier, thereby significantly suppressing carrier recombination and improving the catalytic generation efficiency of ROS. Furthermore, oxygen vacancies introduced through defect engineering can construct electron traps and increase the electron density of the reaction center atoms, further inhibiting carrier recombination and optimizing catalytic performance. This lays the theoretical foundation for designing field-responsive sonicators to achieve highly efficient anti-biofilm therapy. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the existing technology and provide a copper / oxygen-deficient barium titanate piezoelectric heterojunction nanoparticle. Based on the "electronic lever" system of copper and oxygen-deficient barium titanate heterojunction, it can be used for wound repair by precisely controlling the "antibacterial-promoting" sequential treatment.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides a copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticle, wherein the nanoparticle has a tetragonal barium titanate core and an oxygen-defect amorphous layer as a shell, and Cu-Cu is deposited on the surface of the shell. + Nanoclusters form heterojunctions.

[0006] Copper is an essential trace element for the body, and its effects are dose-dependent. Trace amounts of copper ions have been shown to promote angiogenesis and tissue repair. However, abnormal intracellular copper accumulation can interfere with the esterification process in the tricarboxylic acid cycle (TCA). As a transition metal with reactive d-orbital electrons, copper can catalyze the production of reactive oxygen species (ROS) through Fenton-like reactions, and its catalytic activity is highly dependent on the local electron density of the reaction center atom. Although methods to increase electron density through exogenous electron injection have been extensively studied, uncontrolled electron accumulation can easily trigger side reactions. The ideal strategy is to transfer charge from non-reactive center atoms to the reaction center atoms; however, driving the directional migration of valence electrons under the strong confinement of the atomic potential field is extremely challenging. This invention designs and introduces copper to construct a metal / semiconductor heterostructure. Through exploratory experiments, a copper / oxygen-defective barium titanate piezoelectric heterostructure nanoparticle was finally obtained. The copper / oxygen-deficient barium titanate piezoelectric heterojunction nanoparticles of this invention, also known as piezoelectric heterojunction nanozymes, are enhanced nanozymes with an "electronic lever" effect. This effect originates from the oxygen-deficient core-shell structure on the barium titanate surface and its interaction with heterovalent copper nanoclusters (Cu-Cu). + The heterojunction structure formed by barium titanate is activated by ultrasound. The piezoelectric field generated by barium titanate acts as a lever, driving subsequent electronic behavior. The oxygen-defective amorphous layer acts as a fulcrum, reinforcing and guiding charge transfer. This amorphous layer acts as an electron trap, suppressing electron-hole recombination and improving electron utilization efficiency. Furthermore, its strain, higher than that of the crystalline phase, further enhances the piezoelectric effect. Under this synergistic effect, electrons are efficiently driven and enriched on the copper side, which has a lower Fermi level, significantly increasing the local electron density at the copper reaction center. For Cu... + Electron enrichment lowers the activation energy barrier of its catalytic reaction, thereby promoting the decomposition of H2O2 into •OH, while regenerating Cu. 2+ As for Cu 0 The high electron density facilitates the transfer of electrons to the adsorbed H2O2 molecules, thereby stimulating a Fenton-like reaction and continuously replenishing the more catalytically active Cu. + The increase in local electron density directly lowers the activation energy of the peroxidase reaction, ultimately leading to a surge in the generation of ROS and copper ions. Through the synergistic amplification effect of ROS and copper ions, even below the safe threshold concentration, copper ions can flood into the interior of bacteria with altered membrane permeability, inducing "copper-like death" in bacteria by interfering with the TCA cycle and electron transport chain, thus achieving highly efficient antibacterial activity.

[0007] Simultaneously, this material also exhibits good glutathione peroxidase (GSH-Px)-like activity, effectively clearing highly expressed glutathione (GSH) from wounds and assisting in antibacterial treatment. While rapidly depleting the antioxidant GSH, Cu... 2+ Reduced to Cu + , forming dynamic Cu2+ / Cu + Cyclic activity further enhances the peroxidase-like activity of the material. Under static (ultrasound off) conditions, the intrinsic electric field of the heterojunction formed by the directional transfer of electrons driven by the Fermi level difference, in conjunction with the trace release of copper ions, promotes granulation tissue regeneration, collagen deposition, epithelial regeneration, and angiogenesis, thereby synergistically accelerating tissue repair.

[0008] Preferably, the oxygen-deficient amorphous layer is generated by a high-temperature reduction reaction of barium titanate and sodium borohydride.

[0009] Preferably, the Cu-Cu + It is deposited on the surface of an oxygen-defect amorphous layer by in-situ chemical reduction.

[0010] Preferably, the nanoparticles have a particle size of 100 nm-130 nm.

[0011] Preferably, the nanoparticles catalyze the generation of hydroxyl radicals and superoxide anion radicals under ultrasonic excitation.

[0012] The nanoparticles of this invention possess peroxidase-like and glutathione peroxidase activities, and can catalyze the generation of superoxide anion radicals (•O2) under ultrasonic excitation. — ) and hydroxyl radicals (•OH).

[0013] Secondly, the present invention provides a method for preparing the copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticles, comprising the following steps: (1) Barium hydroxide octahydrate and tetrabutyl titanate were mixed and prepared by high temperature and high pressure hydrothermal method to obtain barium titanate nanoparticles with tetragonal crystal structure. (2) Barium titanate nanoparticles and sodium borohydride were mixed and ground, and then heated and calcined under argon protection to form an oxygen-defect amorphous shell on the surface of barium titanate; after cooling, washing and drying, OB nanoparticles were obtained. (3) OB nanoparticles are dispersed in a copper salt solution and mixed with a reducing agent to react and deposit copper elements in situ on the surface of the nanoparticle shell; centrifugation and washing are performed to obtain the copper / oxygen defect barium titanate piezoelectric heterojunction nanoparticles.

[0014] This invention uses barium hydroxide octahydrate (Ba(OH)₂·8H₂O) as the barium source and tetrabutyl titanate as the titanium source to prepare cubic barium titanate (BT) nanoparticles with uniform particle size via a high-temperature, high-pressure hydrothermal method. Then, an amorphous layer (OB) composed of oxygen vacancies is generated on the BT surface through a reaction with sodium borohydride. Finally, heterovalent copper nanoclusters (Cu-Cu) are generated on the OB surface via an in-situ chemical reduction method. + This forms heterojunction nanoparticles (OBC).

[0015] Preferably, step (1) specifically includes the following steps: (a) Dissolve tetrabutyl titanate in anhydrous ethanol, add ammonia dropwise, and stir to form solution A; (b) Dissolve barium hydroxide octahydrate in deionized water and stir until completely dissolved to form solution B; (c) At room temperature, solution A is slowly added dropwise to solution B while stirring. Then diethanolamine is added dropwise and stirring is continued to obtain a mixture. The mixture is placed in a reaction vessel to react and a white suspension is obtained. After centrifugation, the supernatant is discarded to obtain a white precipitate. The precipitate is washed and dried to obtain barium titanate nanoparticles.

[0016] Preferably, in step (2), the mass ratio of barium titanate nanoparticles to sodium borohydride is barium titanate nanoparticles:sodium borohydride = 1:(1.5-2.5).

[0017] Through experimental investigation, this invention has found that when barium titanate nanoparticles and sodium borohydride are combined within the aforementioned range, an amorphous shell of suitable thickness can be obtained, resulting in nanoparticles with good piezoelectric properties. Exceeding the scope of this invention will affect the piezoelectric properties.

[0018] More preferably, in step (2), the mass ratio of barium titanate nanoparticles to sodium borohydride is barium titanate nanoparticles: sodium borohydride = 1:2.

[0019] Preferably, in step (2), the calcination conditions are: heating to 425°C at a heating rate of 5°C / min and calcining for 120 min.

[0020] Preferably, in step (3), the copper salt includes copper chloride or copper nitrate.

[0021] Preferably, the reducing agent comprises sodium borohydride.

[0022] Preferably, in step (3), ultrasound is used to disperse OB nanoparticles in a copper salt solution.

[0023] Thirdly, the present invention provides the application of the copper / oxygen-defective barium titanate piezoelectric heterojunction nanoparticles in the preparation of products or drugs that promote the repair / healing of drug-resistant bacterial infected wounds.

[0024] Preferably, the drug-resistant bacteria include at least one of methicillin-resistant Staphylococcus aureus and Escherichia coli.

[0025] Preferably, the product includes a wound dressing that, in conjunction with ultrasound, promotes wound repair / healing.

[0026] Fourthly, the present invention provides the application of the copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticles in the preparation of antibacterial materials.

[0027] The nanoparticles of this invention can induce "copper-like death" in bacteria, achieving highly efficient antibacterial activity. They also have good glutathione peroxidase (GSH-Px)-like activity, which can effectively clear glutathione (GSH) highly expressed in wounds and assist in antibacterial treatment.

[0028] Preferably, the antibacterial material is an antibacterial material for wounds infected with drug-resistant bacteria.

[0029] Preferably, the drug-resistant bacteria include at least one of methicillin-resistant Staphylococcus aureus and Escherichia coli.

[0030] The beneficial effects of this invention are as follows: The copper / oxygen-deficient barium titanate piezoelectric heterojunction nanoparticles provided by this invention are an enhanced nanozyme with an "electronic leverage" effect. This effect originates from the oxygen-deficient core-shell structure on the barium titanate surface and the heterojunction structure formed with copper. These nanoparticles exhibit an ultrasound-controlled, time-sequential treatment mode, allowing for precise ultrasound-controlled "antibacterial-promoting" time-sequential treatment, which can be used for wound repair.

[0031] Under ultrasound activation, it can rapidly and massively generate ROS and release copper ions. By synergistically disrupting the bacterial cell membrane, tricarboxylic acid (TCA) cycle, and electron transport chain, it causes bacterial energy depletion and induces copper-like bacterial death, achieving highly effective antibacterial effects. Subsequently, during the tissue repair phase, by turning off ultrasound, the intrinsic electric field of the heterojunction and the release of low amounts of copper ions can promote granulation tissue regeneration, collagen deposition, epithelial regeneration, and angiogenesis, thereby synergistically accelerating tissue repair. Attached Figure Description

[0032] Figure 1 Figure 1 shows the phase characterization results of the nanoparticles; Figure 2 shows the scanning electron microscope (SEM) images of BT, OB, and OBC nanoparticles; Figure 3 shows the transmission electron microscope (TEM) images of BT, OB, and OBC nanoparticles; Figure 4 shows the elemental surface energy dispersive spectroscopy (ESD) analysis of OBC nanoparticles; Figure 5 shows the electron paramagnetic resonance (EPR) detection of BT, OB, and OBC; Figure 6 shows the particle size analysis of BT, OB, and OBC; Figure 7 shows the Zeta potential detection of BT, OB, and OBC; Figure 8 shows the X-ray photoelectron spectroscopy (XPS) spectrum of OBC. .

[0033] Figure 2 Figure 1 shows the piezoelectric and electrochemical performance characterization results; Figure 2 shows the piezoelectric response amplitude curve of OBC; Figure 3 shows the phase curve of OBC; Figure 4 shows the effective longitudinal piezoelectric coefficient of OBC. d 33 Figure d shows the cyclic voltammetry (CV) curve; Figure e shows the chemical impedance spectroscopy (EIS); Figure f shows the ultrasonic current density; and Figure g shows the ICP curve of copper ion release.

[0034] Figure 3 The results are for peroxidase-like performance testing; (a) fluorescence spectra and (b) fluorescence intensity of different concentrations of OBC reacted with H2O2 by TA detection; (c) •O2 — ESR spectrum of (d)•OH; ESR spectrum of (d)•OH.

[0035] Figure 4 The results are for the detection of glutathione peroxidase activity; (a) UV-Vis absorption spectra and (b) percentages of GSH and GSSG after the reaction of different concentrations of OBC with GSH were detected by DTNB.

[0036] Figure 5 Figure a shows the results of antibacterial performance testing; Figure a shows the results of different treatment groups. E. Coli Image of bacterial colonies; Image b shows different treatment groups. E. Coli Relative bacterial activity; Figure c shows MRSA colony images after different treatment groups; Figure d shows the relative bacterial activity of MRSA after different treatment groups; in the figures .

[0037] Figure 6 The figures show the results of full-thickness skin wound repair in rats with MRSA infection; Figure a shows skin wound images on days 0, 3, 7, and 12 after treatment in different groups; Figure b shows the wound healing rate on days 3, 7, and 12 after treatment in different groups; Figure c shows bacterial colony images from infected wounds after treatment in different groups; . Detailed Implementation

[0038] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0039] Unless otherwise specified, the experimental methods used in this invention are conventional methods, and the materials and reagents used are commercially available products that can be obtained through commercial channels.

[0040] Example 1: Synthesis of copper / oxygen-defect barium titanate (OBC) piezoelectric heterojunction nanoparticles This invention uses barium hydroxide octahydrate (Ba(OH)₂·8H₂O) as the barium source and tetrabutyl titanate as the titanium source to prepare cubic barium titanate (BT) nanoparticles with uniform particle size via a high-temperature, high-pressure hydrothermal method. Then, an amorphous layer (OB) composed of oxygen vacancies is generated on the BT surface through a reaction with sodium borohydride. Finally, heterovalent copper nanoclusters (Cu-Cu) are generated on the OB surface via an in-situ chemical reduction method. + ) to form heterojunction nanoparticles (OBC) Figure 1 a).

[0041] The specific preparation method is as follows: 1. Synthesis of barium titanate (BT) nanoparticles: BT nanoparticles were prepared by a high-temperature, high-pressure hydrothermal method. 1) Dissolve 25 mmol of tetrabutyl titanate in 20 mL of anhydrous ethanol, slowly add 5 mL of ammonia water to the solution and stir continuously for 15 min to form solution A; 2) Dissolve 35 mmol of barium hydroxide octahydrate in 25 mL of deionized water and stir in a water bath at 90°C until completely dissolved to form solution B; 3) At room temperature, slowly add solution A to solution B dropwise, stir for 15 min, then add 5 mL of diethanolamine dropwise, and continue stirring for 15 min; put the mixture into a reaction vessel and react at 200℃ for 48 h. 4) Centrifuge the white suspension obtained from the reaction at 8000 rpm, discard the supernatant to obtain a white precipitate, wash it alternately with anhydrous ethanol and deionized water and centrifuge it three times at 10000 rpm for 10 min each time; finally, dry the precipitate at 60℃ for 24 h to obtain tetragonal BT nanoparticles with a particle size of about 70~110 nm.

[0042] 2. Synthesis of oxygen-deficient core-shell barium titanate (OB) nanoparticles: OB nanoparticles are formed by constructing an oxygen-defect amorphous layer on the surface of BT using a high-temperature reduction technique.

[0043] Specifically, BT nanoparticles were mixed with sodium borohydride (NaBH4) at a mass ratio of 1:2 and ground for 10 min. Subsequently, under argon protection, the mixture was heated to 425 °C in a tube furnace at a heating rate of 5 °C / min and calcined for 120 min. After natural cooling, the mixture was repeatedly washed with deionized water and anhydrous ethanol to remove excess NaBH4. Finally, it was dried in an oven for 24 h to obtain OB nanoparticles with a particle size of approximately 90–120 nm. The OB nanoparticles consist of an amorphous oxygen defect structure as a shell, encapsulating tetragonal barium titanate nanoparticles.

[0044] 3. Synthesis of copper / oxygen defective core-shell barium titanate heterojunction (OBC) nanoparticles: Cu-Cu was grown on the surface of OB nanoparticles using in-situ redox technology. + Copper nanoclusters.

[0045] Specifically, 0.3 g of OB nanoparticles were added to 50 mL of a 0.02 mM copper chloride (CuCl2) (or copper nitrate CuNO3) solution and ultrasonically vibrated for 10 min to ensure uniform dispersion of OB in the solution. Then, the resulting mixture was mixed with a 0.5 mM NaBH4 solution at a volume ratio of 1:1.5. After reacting at room temperature for 30 min, the mixture was immediately centrifuged at 10,000 rpm for 10 min and washed with deionized water and anhydrous ethanol. Finally, the mixture was dried at 60 °C for 24 h to obtain OBC nanoparticles with a particle size of approximately 100–130 nm.

[0046] Example 2: Phase characterization of copper / oxygen-defect barium titanate (OBC) piezoelectric heterojunction nanoparticles The OB and OBC nanoparticles prepared in Example 1 were characterized, observed, and tested.

[0047] Transmission electron microscopy revealed a uniform amorphous oxygen defect layer on the surface of OB nanoparticles, and 2-3 nm copper nanoclusters were grown in situ on the surface of OBC nanoparticles. Figure 1 b). Transmission electron microscopy (TEM) energy dispersive spectroscopy analysis confirmed that the prepared OBC nanoparticles contained not only Ti, O, and Ba elements, but also Cu element (…). Figure 1 c).

[0048] Electron paramagnetic resonance (EPR) spectroscopy results show that ( Figure 1 d) An EPR signal at g = 2.003 can be observed in OB and OBC, indicating the presence of a large number of lattice defects on the barium titanate surface, further confirming the successful construction of an oxygen defect layer in OB and OBC.

[0049] Dynamic light scattering (DLS) results show that the hydrodynamic diameter of OBC is slightly increased compared to BT and OB. Figure 1 e). At the same time, the absolute value of the Zeta potential also decreased slightly ( Figure 1 f). This further demonstrates that copper nanoclusters were successfully generated on the surface of OB nanoparticles, forming OBC nanoparticles.

[0050] X-ray photoelectron spectroscopy (XPS) results showed ( Figure 1 (g) Two peaks were separated in the O 1s spectrum of OBC, located at 530.25 eV and 529.72 eV, corresponding to oxygen vacancies and lattice oxygen, respectively, confirming the presence of oxygen vacancies. In the 2p orbitals of copper, the XPS spectrum of OBC showed two orbitals (952.35 eV and 932.54 eV), with the spin orbitals splitting at 19.81 eV, which were assigned to two energy levels, Cu 2p1 / 2 and Cu 2p3 / 2, respectively, accompanied by two vibrational satellite peaks.

[0051] Example 3: Characterization of the piezoelectric and electrochemical properties of OBC The ferroelectricity of OBC nanoparticles was detected by piezoelectric microscopy (PFM). The amplitude diagram ( Figure 2 In a), a typical butterfly-shaped amplitude hysteresis loop can be observed; in the phase diagram ( Figure 2 In (b), the local piezoelectric phase curve of the OBC nanoparticles shows a 180° phase switch, indicating the excellent piezoelectric response of OBC. Furthermore, the effective longitudinal piezoelectric coefficient of OBC is obtained by fitting the slope of the piezoelectric response amplitude signal. d 33 Approximately 31.64 pm / V ( Figure 2 c).

[0052] Electron migration in heterojunctions is crucial for the release of copper ions and the generation of reactive oxygen species (ROS). Therefore, the electrochemical performance of the heterojunction material was tested. An oxidation peak was observed in the CV curve of the OBC, indicating that copper was oxidized to copper ions and released. Figure 2 d). No oxidation peaks were observed in BT and OB because no copper was oxidized.

[0053] EIS chart ( Figure 2 e) It can be seen that in the high-mid frequency region, the radius of the OBC arc is the smallest, indicating that its charge transfer impedance is low; secondly, in the low frequency region, the angle between the OBC and the real axis is larger, indicating that it improves the ion transport rate and electrochemical capacitance.

[0054] The ultrasonic current density results show that ( Figure 2 f), OBC exhibits the highest average ultrasonic current density, indicating greater electron transfer within it. This is attributed to the combined effect of the oxygen defect structure and the piezoelectric heterojunction.

[0055] Furthermore, inductively coupled plasma atomic emission spectrometry (ICP) results showed that ( Figure 2 g), under ultrasonic loading, the amount of copper ions released in the OBC+US group increased instantaneously compared to the OBC group, and finally stabilized at around 0.78 mg / L.

[0056] Example 4: Detection of OBC-type peroxidase activity and types of ROS produced by catalysis Mix 5 µL of terephthalic acid (TA) (5 mM, dissolved in 2 mM NaOH), 50 µL of hydrogen peroxide (H2O2) (1 mM), and 25 µL of OBC (0 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL, 500 μg / mL), and sonicate under light-protected conditions (2 W / cm²). 2The excitation wavelength was 2.0 MHz, 50% duty cycle, for 10 min, followed by incubation for another 10 min. Fluorescence spectra were recorded under excitation wavelengths of 315 nm and emission wavelengths of 350–600 nm. To detect reactive oxygen species generated by OBC catalysis, 5,5-dimethyl-1-pyrrolidone N-oxide (DMPO) was used as a spin trapping agent for electron spin resonance (ESR) spectroscopy to capture superoxide anion radicals (•O2). — ) and hydroxyl radicals (•OH).

[0057] The results showed that the group with added OBC exhibited a significant peak at approximately 425 nm, indicating that •OH was produced in large quantities. Simultaneously, dose-dependent catalytic activity was demonstrated. Figure 3 ab). Electron spin resonance (ESR) results show that the OBC+US group also exhibits a peak in •O2. — ( Figure 3 c). At the same time, Figure 3 As shown in d, the OBC+US group exhibits four distinct characteristic peaks (1:2:2:1), indicating the catalytic production of a large amount of •OH. These results collectively demonstrate that the construction of oxygen vacancies and piezoelectric heterojunctions in OBC jointly promotes carrier separation and significantly improves the efficiency of ROS catalytic production under ultrasonication.

[0058] Example 5: Detection of OBC-type glutathione peroxidase activity Using 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) as a probe, the -SH group of residual glutathione (GSH) can be detected. Specifically, OBC (0 μg / mL, 50 μg / mL, 100 μg / mL, 200 μg / mL, 500 μg / mL) was incubated with GSH (0.5 mM) at 37 °C for 30 min. Then, 5 mM DTNB (dissolved in 50 mM Tris-HCl) was added and reacted for 10 min. The UV-Vis absorption spectrum of the mixture was measured, and the OD value of the supernatant at 412 nm was determined.

[0059] Figure 4 a and Figure 4 b shows that as the OBC concentration increases, the amount of TNB generated by the reaction with GSH gradually decreases, indicating that GSH consumption gradually increases and is positively correlated with copper loading.

[0060] Example 6: Antibacterial performance test Take Escherichia coli in the logarithmic growth phase ( E. Coli ) and methicillin-resistant Staphylococcus aureus (MRSA) bacterial suspensions, the bacterial suspension concentration was diluted to 10. 7CFU / mL. Different treatments were administered according to group: NC group (blank), NC+US (blank + sonication), OB (OB nanoparticle treatment), OB+US (OB nanoparticle + sonication), OBC (OBC nanoparticle treatment), and OBC+US (OBC nanoparticle + sonication). The concentrations of OB and OBC were 20 μg / mL, and the sonication (US) treatment parameters were 2 W / cm². 2 2.0 MHz, 50% duty cycle, 10 min. After co-culturing for 8 h, the bacterial culture was inoculated onto LB agar plates and incubated at 37°C for 12 h before colony counting.

[0061] pass E. Coli ( Figure 5 a) and MRSA Figure 5 c) As shown in the colony plate images, the number of colonies in the OBC+US group was significantly lower than that in the other groups. OBC+US... E. Coli The antibacterial rates of MRSA and MRSA were 99.85 ± 0.08% respectively. Figure 5 b) and 99.88 ± 0.21% Figure 5 d).

[0062] Example 7: Healing of infectious skin defects in rats Male SPF-grade SD rats aged 8-10 weeks, weighing 200 ± 50 g, were randomly divided into 5 groups: PC group, NC group, OBC group, and OBC+US group. Anesthesia was administered via intraperitoneal injection of 3% sodium pentobarbital at a dose of 50 mg / kg. The surgical area (6 × 6 cm) on the rat's back was shaved preoperatively for skin preparation. The back skin was disinfected with 0.5% povidone-iodine, and then two circular full-thickness skin wounds (10 mm in diameter) were made on the rat's back using a sterilized skin punch. 50 μL of MRSA bacterial solution (10... 8 A trauma infection model was established by injecting CFU / mL into the wound to simulate an infected wound.

[0063] After a 24-hour observation period to confirm successful infection model establishment, treatment was administered according to group assignments. The PC group received commercially available 3MTegaderm for wound treatment. TM After treatment, gauze was applied to the wound; in the NC group, no other treatment was given, only gauze was applied; in the OBC group, the wound was treated with OBC suspension (20 μg / mL) and then covered with gauze; in the OBC+US group, the wound was treated with OBC and then covered with gauze, and ultrasound treatment (2 W / cm²) was performed twice daily for the first 5 days after treatment. 2(2.0 MHz, 50% duty cycle, 10 min). Wound changes were observed and photographed on days 3, 7, and 12 post-treatment. Wound area was measured using ImageJ software, and wound healing rate was calculated. Simultaneously, wound exudate was collected on day 3, diluted with PBS, and inoculated onto LB agar plates. Colony counts were observed after overnight incubation.

[0064] like Figure 6 As shown in Figure a, throughout the treatment process, the OBC+US group consistently exhibited a faster healing process than other groups, with relatively drier wounds and a significantly reduced wound area. By day 12, the wounds in the OBC+US group had almost completely healed, with a healing rate as high as 97.95 ± 0.86%. Figure 6 b). Meanwhile, the number of colonies in the OBC+US group was significantly reduced ( Figure 6 c).

[0065] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticle, characterized in that, The nanoparticles have a tetragonal barium titanate core and an oxygen-defect amorphous layer as a shell, with Cu-Cu deposited on the shell surface. + Nanoclusters form heterojunctions.

2. The copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticles as described in claim 1, characterized in that, The nanoparticles have a particle size of 100 nm-130 nm.

3. The copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticles as described in claim 1, characterized in that, The nanoparticles catalyze the generation of hydroxyl radicals and superoxide anion radicals under ultrasonic excitation.

4. A method for preparing copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticles as described in any one of claims 1-3, characterized in that, Includes the following steps: (1) Barium hydroxide octahydrate and tetrabutyl titanate were mixed and prepared by high temperature and high pressure hydrothermal method to obtain barium titanate nanoparticles with tetragonal crystal structure. (2) Barium titanate nanoparticles and sodium borohydride are mixed and ground, and then heated and calcined under argon protection to form an oxygen-defect amorphous shell on the surface of barium titanate. Cooling, washing, and drying yield OB nanoparticles; (3) OB nanoparticles are dispersed in a copper salt solution and mixed with a reducing agent to react, thereby depositing copper elements in situ on the surface of the nanoparticle shell. Centrifugation and washing yielded the copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticles.

5. The method as described in claim 4, characterized in that, In step (2), the mass ratio of barium titanate nanoparticles to sodium borohydride is barium titanate nanoparticles: sodium borohydride = 1: (1.5-2.5).

6. The method as described in claim 4, characterized in that, In step (3), the copper salt includes copper chloride or copper nitrate; the reducing agent includes sodium borohydride.

7. The use of the copper / oxygen-deficient barium titanate piezoelectric heterojunction nanoparticles as described in any one of claims 1-3 in the preparation of products or drugs that promote the repair / healing of drug-resistant bacterial infected wounds.

8. The application as described in claim 7, characterized in that, The drug-resistant bacteria include at least one of methicillin-resistant Staphylococcus aureus and Escherichia coli.

9. The application as described in claim 7, characterized in that, The product includes wound dressings that, when used with ultrasound, promote wound repair / healing.

10. The application of copper / oxygen-defect barium titanate piezoelectric heterojunction nanoparticles as described in any one of claims 1-3 in the preparation of antibacterial materials.

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