Preparation method and application of magnetic trigger thermoelectric catalysis nano-enzyme
By preparing magnetically triggered thermoelectrocatalytic nanozymes, the problems of catalytic efficiency and blood-brain barrier in the treatment of gliomas were solved by utilizing magnetic drive and thermoelectrocatalytic activity, achieving efficient enrichment and therapeutic effect at the tumor site.
Patent Information
- Application Number
- CN202511461035.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-14
- Publication Date
- 2026-01-09
AI Technical Summary
The efficacy of existing nanozyme catalysis for glioma treatment is limited by catalytic efficiency, concentration of endogenous reaction substrates, and activity of a single nanozyme. Furthermore, traditional preparation methods are complex and difficult to mass-produce, and the blood-brain barrier hinders the delivery of chemotherapy drugs.
A magnetically triggered thermoelectrocatalytic nanozyme was prepared using a one-step cation exchange method. It was then targeted and enriched at the cerebral vascular endothelium by magnetic drive, and its thermoelectrocatalytic activity was triggered by heat under the action of ultrasound and magnetic field. Combined with the specific binding of HA molecules to the tumor cell membrane, the nanozyme was enriched at the tumor site.
This study achieved efficient enrichment and catalysis of nanozymes at tumor sites, disrupting the antioxidant defense mechanisms of tumor cells, significantly inhibiting tumor growth, simplifying the preparation process, and improving therapeutic efficacy.
Smart Images
Figure CN121292374A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of glioma treatment technology, specifically relating to a method for preparing and applying a magnetically triggered thermoelectrocatalytic nanozyme. Background Technology
[0002] Gliomas, as common and refractory primary tumors of the central nervous system (CNS) (accounting for over 80% of CNS malignancies), present significant clinical treatment challenges. Glioblastoma (GBM, WHO grade IV astrocytoma), in particular, is characterized by its highly aggressive nature, and median survival remains difficult to improve significantly even with current comprehensive treatment regimens (including surgical resection, concurrent chemoradiotherapy, and emerging therapies such as targeted therapy). The treatment difficulties of gliomas stem primarily from two aspects: firstly, the invasive growth pattern of tumor cells creates a complex interface with the brain parenchyma, making complete resection difficult even with precise neurosurgical techniques, resulting in a persistently high postoperative recurrence rate; secondly, the presence of the blood-brain barrier (BBB) severely hinders the effective delivery of chemotherapeutic drugs, making it difficult for conventional cytotoxic drugs to reach therapeutic concentration thresholds. Therefore, developing novel targeted drugs that possess both high BBB penetration capability and effective tumor cell killing has become a pressing scientific challenge in the current field of glioma treatment.
[0003] Nanozymes, as artificial intelligence enzymes, ingeniously combine the unique physicochemical properties of nanomaterials with the catalytic activity of natural enzymes. They exhibit unique advantages in regulating cellular metabolic reprogramming, energy homeostasis imbalances, and intervening in pathological processes, and have become a core tool for precise biological regulation, replacing natural enzymes. However, the efficacy of nanozyme-catalyzed therapy is currently limited by many factors, such as the catalytic efficiency of nanozymes, the concentration of endogenous reaction substrates, and the low activity of single nanozymes. Importantly, under the influence of physical stimuli such as sound and magnetism, ultrasound and magnetic fields generate cavitation and thermal effects, releasing energy to locally generate certain temperatures and pressures, thereby accelerating the reaction process. Notably, the enzymatic reaction process of nanozymes mainly depends on the acidic, high glutathione (GSH), and high hydrogen peroxide (H2O2) concentrations of the tumor microenvironment. This microenvironmental responsiveness can not only trigger multiple cascade enzymatic processes but also regulate the metabolic network homeostasis of tumor cells based on the characteristics of natural enzymes, thereby interfering with the metabolic level of tumor cells and inhibiting tumor growth. By focusing on a quadruple catalytic network of peroxidase activity (POD-like), NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activity (Nox-like), L-cysteine oxidase activity (LCO-like), and lactate dehydrogenase (LDH-like) activity, not only can a cascade reaction be achieved to trigger a strong ROS storm, but it also consumes reducing cellular metabolism and destroys the cell's antioxidant defense mechanism. This strong and continuous cellular oxidative stress causes tumor cell death.
[0004] Traditional methods for preparing composite nanomaterials typically employ electrostatic adsorption or in-situ growth. First, electrostatic adsorption often requires the separate preparation of two individual materials. By measuring or modifying their potentials, positive and negative charges are assigned to each material, respectively. The composite nanomaterial is then obtained through the attraction of these charges in an aqueous solution. This method is complex, cumbersome, and difficult to scale up for mass production. Second, in-situ growth is a composite material preparation technique that directly generates a reinforcing phase within or on the surface of a matrix material through chemical reactions or physical processes. This method involves the introduction of multiple precursors, with the chemical reaction or physical deposition of these precursors triggered by controlled reaction conditions. Because of the multiple precursors involved, interactions between them can occur during the preparation process, significantly reducing the success rate of composite material preparation. Furthermore, this method is time-consuming, impacting the efficiency of material preparation. Summary of the Invention
[0005] The purpose of this invention is to provide a method for preparing and applying magnetically triggered thermoelectrocatalytic nanozymes, which can be targeted and enriched at the cerebral vascular endothelium through magnetic drive, and the heat generated by the LFSH nanozyme under the action of AMF triggers its own thermoelectrocatalytic activity, thereby playing an anti-tumor therapeutic role.
[0006] The specific technical solution adopted by this invention is as follows: A method for preparing magnetically triggered thermoelectrocatalytic nanozymes, the method comprising the following steps: S1: Preparation of magnetic nanozyme FeTe2; The preparation method in S1 is as follows: S11: Disperse 1.0 mmol of Fe(acac)3 in a 100 mL three-necked flask containing 20 mL of oleylamine, and heat it from room temperature to 180 °C under magnetic stirring, and keep it at 180 °C for 30 min. S12: Dissolve 3 mmol of Te particles in 5 mL of trioctylphosphine (TOP) in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the above three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. S13: Maintain at 300℃ for 60 min. After the reaction is completed and cooled to room temperature, add anhydrous ethanol to cause the nanoparticles to precipitate. Wash the nanoparticles three times with cyclohexane and anhydrous ethanol. Centrifuge at 12000 rpm for 15 min to obtain FeTe2 nanoparticles.
[0007] S2: Rare earth element Lu-doped magnetic nanoenzyme Lu x Fe 1-x Preparation of Te2; Magnetic nanozyme Lu in S2 x Fe 1-x The specific method for preparing Te2 is as follows: S21: Magnetic nanozymes with Lu doping levels of 0.5%, 1.0%, 1.5%, and 2.0% were prepared, respectively. x Fe 1-x Te2; S22: Disperse 1-x mmol of Fe(acac)3 and x mmol of Lu(acac)3 in a 100 mL three-necked flask containing 20 mL of OM, and heat from room temperature to 180 °C under magnetic stirring, and maintain at 180 °C for 30 min. S23: Dissolve 3 mmol of Te particles in 5 mL of TOP in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. S24: Maintain the reaction at 300℃ for 60 min. After cooling to room temperature, add anhydrous ethanol to cause the nanoparticles to precipitate. Wash the nanoparticles three times with cyclohexane and anhydrous ethanol, and centrifuge at 12000 rpm for 15 min to obtain Lu. 0.01 Fe 0.99Te2 nanoparticles.
[0008] S3: Preparation of magnetically triggered thermoelectrocatalytic nanozyme LFS; In step S3, LFS magnetically triggered thermoelectrocatalytic nanozymes are prepared via a one-step cation exchange method, as detailed below: S31: Disperse 0.99 mmol of Fe(acac)3 and 0.01 mmol of Lu(acac)3 in a 100 mL three-necked flask containing 20 mL of OM, and heat from room temperature to 180 °C under magnetic stirring, and maintain at 180 °C for 30 min. S32: Dissolve 3 mmol of Te particles in 5 mL of TOP in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. Maintain the temperature at 300 °C for 60 min. After the reaction is complete, quickly reduce the temperature of the reaction system to 200 °C. S33: Weigh 0.3 mmol SnCl2·2H2O and dissolve it in 4 mL of diethylene glycol. After sonicating it to completely disperse and dissolve, add it to the above mixed solution at 200℃ and react at 200℃ for 30 min by cation exchange method. S34: After the reaction is completed and cooled to room temperature, anhydrous ethanol is added to cause the nanoparticles to precipitate. The nanoparticles are washed three times with cyclohexane and anhydrous ethanol, and centrifuged at 12,000 rpm for 15 min to obtain LFS nanoparticles.
[0009] By adding different proportions of Sn source SnCl2·2H2O, LFS with different magnetocaloric and thermoelectric catalytic properties was investigated.
[0010] S4: Preparation of magnetically triggered thermoelectrocatalytic nanoenzyme LFSH; The specific preparation method of the magnetically triggered thermoelectrocatalytic nanozyme LFSH in S4 is as follows: S41: 35mg of Lu 0.01 Fe 0.99 Te2@SnTe was dispersed in 30 mL of cyclohexane, and 3.5 mg of PEI was dispersed in 30 mL of anhydrous ethanol. The two were added dropwise and mixed under ultrasonication. The mixture was stirred overnight in a shaker at 180 rpm. The product was collected by centrifugation, washed three times with ultrapure water, and then redispersed in 30 mL of ultrapure water. S42: Disperse 175 mg of HA in 30 mL of ultrapure water, add the above product aqueous solution dropwise to the HA aqueous solution under ultrasonication, mix and shake in a shaker at 180 rpm for 24 h, collect the product by centrifugation after the end, wash the product three times with ultrapure water, and finally place it in a freeze dryer for freeze drying to obtain LFSH.
[0011] S5: In vitro antitumor effect of magnetically triggered thermoelectrocatalytic nanozyme LFSH.
[0012] S5 also includes: Biosafety of magnetically triggered thermoelectrocatalytic nanoenzymes LFSH; Evaluation of the uptake capacity of GL261 cells of magnetically triggered thermoelectrocatalytic nanozyme LFSH; Evaluation of magnetically driven BBB penetration of LFSH nanozymes; Evaluation of the killing effect of LFSH nanozymes on GL261 cells.
[0013] S6: In vivo antitumor effect of magnetically triggered thermoelectrocatalytic nanozyme LFSH.
[0014] The specific in vivo anti-tumor effects of LFSH are as follows: An in situ glioblastoma model was successfully constructed by injecting GL261-LUC tumor cells into the brain region of C57BL / 6J mice at approximately 7 weeks of age. The nanozyme was administered via tail vein, and ultrasound stimulation and magnetothermal therapy were applied. To monitor the treatment effect in tumor-bearing mice during the treatment cycle, D-fluorescein potassium salt was injected intraperitoneally and observed using an animal in vivo imaging system. The groups are as follows: (G1) PBS+US+AMF; (G2) LFSH; (G3) LFSH+Magnet; (G4) LFSH+US+Magnet; (G5) LFSH+AMF+Magnet; (G6) LFSH+US+AMF+Magnet.
[0015] An application of a magnetically triggered thermoelectrocatalytic nanozyme, utilizing the multiple enzyme activities of LFSH nanozymes, for the treatment of glioma.
[0016] The technical effects achieved by this invention are as follows: The present invention discloses a method for preparing and applying a magnetically triggered thermoelectrocatalytic nanozyme, which is prepared by a one-step cation exchange method. This method greatly reduces the preparation time of the composite nanozyme and simplifies the preparation process. By simply introducing a single Sn cation and adjusting the temperature and time of the cation exchange, a magnetically triggered thermoelectrocatalytic nanozyme with both good magnetocaloric and pyroelectrocatalytic properties can be obtained in a short reaction time.
[0017] This invention discloses a method for preparing and applying magnetically triggered thermoelectrocatalytic nanozymes. Utilizing the magnetic properties of nanozymes, a static magnetic field is used to enrich LFSH nanozymes near the blood-brain barrier (BBB), formed by capillary endothelial cells, the basement membrane, and astrocyte foot processes. Subsequently, the magnetic LFSH nanozymes, through the action of an ammonia-stimulating factor (AMF), generate localized high temperatures, temporarily and reversibly opening the BBB, allowing the LFSH nanozymes to enter the intracranial space. Furthermore, modified HA molecules enable specific binding to CD44 receptors on tumor cell membranes, maximizing the accumulation of nanozymes at the tumor site.
[0018] The present invention discloses a method for preparing magnetically triggered thermoelectrocatalytic nanozymes and their application in treatment. Through magnetic driving, the nanozymes are targeted and enriched at the cerebral vascular endothelium, and the heat generated by the LFSH nanozymes under the action of AMF triggers their own thermoelectrocatalytic activity, achieving a dual therapeutic effect. The multiple enzyme activities of LFSH nanozymes also have a good effect on the treatment of glioma. Attached Figure Description
[0019] Figure 1 These are SEM images of the magnetic nanoenzyme FeTe2 with different Fe / Te ratios and different reaction times of the present invention; Figure 2 The images show the XRD patterns and magnetocaloric heating curves of the magnetic nanoenzyme FeTe2 with different Fe / Te ratios and different reaction times of this invention. Figure 3 This invention relates to Lu doped with different rare earth elements. x Fe 1-x SEM and DLS images of Te2 magnetic nanozymes; Figure 4 This invention relates to Lu doped with different rare earth elements. x Fe 1-x (a) XRD pattern of Te2 magnetic nanozyme; (b, c) magnetocaloric heating curves; (d) calculation of magnetocaloric conversion efficiency SAR value; (e) infrared thermal image; Figure 5 The present invention includes (a) XRD patterns of nanozymes with different cation replacement times; (b) XRD patterns of nanozymes with different Sn source replacement ratios; (c) SEM images; (d) magnetocaloric heating curves; (e) calculation of magnetocaloric conversion efficiency (SAR) values; and (f) infrared thermal imaging images. Figure 6 This invention (ae) describes magnetically triggered nanozymes with different Sn source substitution ratios. 0.01 Fe 0.99 Thermoelectrocatalytic performance of Te2@SnTe in generating •OH for the degradation of methylene blue MB: UV-Vis plot and (f) statistical graph; Figure 7This invention is a magnetically triggered thermoelectric nanoenzyme Lu. 0.01 Fe 0.99 Band structure characterization of Te2@SnTe; Figure 8 The present invention includes (a) Zeta potential diagrams of magnetically triggered thermoelectric nanoenzymes LFSH modified with different proportions of HA; (b) XRD pattern; and (c) DLS pattern. Figure 9 This is the hysteresis loop characterization of the magnetically triggered thermoelectrocatalytic nanoenzyme LFSH of this invention; Figure 10 The magnetocaloric performance characterization of the magnetically triggered thermoelectrocatalytic nanoenzyme LFSH of this invention includes: (a) magnetocaloric heating curves at different concentrations, (b) calculation of magnetocaloric conversion efficiency (SAR) value, (c) infrared thermal imaging; (d) magnetocaloric heating curves at different magnetic field strengths, (e) infrared thermal imaging; and (f) magnetocaloric cycling stability. Figure 11 This is the SDT of the present invention. 1 O2 generation capacity; (a) Degradation of DPBF by water in the control group; (b) LF generated under the action of US. 1 (c) Degradation of DPBF by O2; (d) LFSH produced under the influence of US 1 O2 degradation of DPBF (d) LFSH produced under the influence of US and ΔT 1 O2 degradation of DPBF and (e) corresponding statistical graphs; (f) DMPO capture at different temperatures. 1 ESR spectrum of O2 signal; Figure 12 The thermoelectric properties of LFSH and SnTe in this invention are as follows: (a) Electrical conductivity; (b) Seebeck coefficient; (c) Power factor; (d) Thermal conductivity; (e) ZT value; (f) Radar plot of the five thermoelectric parameters. Figure 13 This invention includes: (a) Nyquist plots of electrochemical impedance spectroscopy (EIS) for LF, LFSH, and SnTe under heating-cooling cycles; (b) pyroelectric currents of LF, LFSH, and SnTe under heating-cooling cycles; (ce) •OH generation performance during the PECT process; (j) degradation of MB by LSFH nanozymes under different heating-cooling cycles under AMF; and (e) ESR spectra of •OH signals captured by 2,2,6,6-tetramethylpiperidine (TEMP) under heating-cooling cycles. Figure 14 The present invention includes (a) the TMB colorimetric reaction detection of •OH generation under different stimulation conditions at pH=5.5; and (b) the ESR spectrum of •OH signal captured by TEMP. Figure 15This invention (ad) uses L-Cys as a substrate to detect the LCO-like oxidase activity of LFSH nanozymes under different stimulation conditions and its (b) corresponding statistical graph. Figure 16 This invention (a) detects the Nox-Like activity of LFSH nanozymes using NADPH as a substrate; (b) compares and analyzes the degradation of NADPH by LFSH nanozymes under different stimulating conditions. Figure 17 The present invention is an L-lactic acid kit for detecting lactate consumption at different LFSH concentrations; (a) LDH-Like activity analysis of LFSH nanozymes under different stimulation conditions and (b) activity analysis at different concentrations; Figure 18 The present invention demonstrates the cytotoxicity of the magnetically triggered thermoelectrocatalytic nanozyme LFSH to bEnd.3, L929, and 3T3 cells. Figure 19 This is an image of CLSM uptake by GL261 cells of the magnetically triggered thermoelectrocatalytic nanozyme LFSH-FITC. Figure 20 These are the corresponding fluorescence CLSM images of GL261 cells in the subventricular space at different time points according to the present invention; Figure 21 The present invention demonstrates (a) the killing ability of magnetically triggered thermoelectrocatalytic nanoenzyme LFSH at different concentrations on GL261 cells; and (b) the killing ability of GL261 cells under different stimulation conditions at the same concentration. Figure 22 The present invention provides fluorescence images generated by the DCFH-DA probe for detecting ROS after applying different stimulation conditions to the magnetically triggered thermoelectrocatalytic nanozyme. Figure 23 This is a bioluminescence signal map of the brain of C57BL / 6J mice during the treatment period of this invention. Detailed Implementation
[0020] To make the objectives and advantages of this invention clearer, the invention will be specifically described below with reference to embodiments. It should be understood that the following text is merely used to describe one or more specific embodiments of the invention and does not strictly limit the scope of protection specifically claimed by the invention.
[0021] like Figure 1 As shown, a method for preparing a magnetically triggered thermoelectrocatalytic nanozyme includes the following steps: S1: Preparation of magnetic nanozyme FeTe2; The specific preparation method in S1 is as follows: S11: Disperse 1.0 mmol of Fe(acac)3 in a 100 mL three-necked flask containing 20 mL of oleylamine (OM), and heat from room temperature to 180 °C under magnetic stirring, and maintain at 180 °C for 30 min. S12: Dissolve 3 mmol of Te particles in 5 mL of trioctylphosphine (TOP) in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the above three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. S13: The reaction was maintained at 300℃ for 60 min. After cooling to room temperature, anhydrous ethanol was added to allow the nanoparticles to settle. The nanoparticles were then washed three times with cyclohexane and anhydrous ethanol, and centrifuged at 12000 rpm for 15 min to obtain FeTe2 nanoparticles. Based on this, the effects of different Fe / Te ratios and reaction times on the morphology, structure, and properties of the nanoparticles were investigated.
[0022] Characterization of FeTe2 magnetic nanozymes: like Figure 1 and Figure 2 As shown, different FeTe2 magnetic nanozymes were obtained by adjusting the ratio of Fe and Te sources and the synthesis reaction time. SEM images show that the nanoparticle size tends to decrease with increasing reaction time. With increasing Fe / Te source ratio (from Fe / Te=1:1 to Fe / Te=1:4), the particle morphology becomes increasingly regular, exhibiting a cubic lamellar structure.
[0023] XRD images showed that FeTe2 magnetic nanozymes could be prepared with different reaction times and different Fe / Te ratios, but the magnetocaloric properties varied. Through XRD, SEM, and magnetocaloric characterization, the FeTe2 magnetic nanozymes with a 1:3 Fe / Te ratio and a reaction time of 60 min were selected as having moderate particle size and good magnetocaloric properties. Therefore, this experimental scheme was used for the preparation of other nanozymes in the future.
[0024] S2: Rare earth element Lu-doped magnetic nanoenzyme Lu x Fe 1-x Preparation of Te2; S2 Magnetic Nanoenzyme Lu x Fe 1-x The specific method for preparing Te2 is as follows: S21: Magnetic nanozymes with Lu doping levels of 0.5%, 1.0%, 1.5%, and 2.0% were prepared, respectively. x Fe 1-x Te2; S22: 1-x mmol of Fe(acac)3 and x mmol of Lu(acac)3 (x=0.005, 0.01, 0.015, 0.02mmol) were dispersed in a 100mL three-necked flask containing 20mL OM, and the temperature was raised from room temperature to 180℃ under magnetic stirring, and held at 180℃ for 30min; S23: Dissolve 3 mmol of Te particles in 5 mL of TOP in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. S24: Maintain the reaction at 300℃ for 60 min. After cooling to room temperature, add anhydrous ethanol to cause the nanoparticles to precipitate. Wash the nanoparticles three times with cyclohexane and anhydrous ethanol, and centrifuge at 12000 rpm for 15 min to obtain Lu. 0.01 Fe 0.99 Te2 nanoparticles.
[0025] Magnetic nanoenzyme Lu x Fe 1-x Characterization of Te2: like Figure 3 and Figure 4 As shown, the magnetocaloric properties of FeTe2 magnetic nanozymes were further improved by doping with the rare earth element Lu. With increasing Lu doping concentration, the magnetocaloric properties of the FeTe2 magnetic nanozymes initially improved and then decreased. At a Lu doping concentration of 1%, the particle size was moderate, the magnetocaloric properties were optimal, and the magnetocaloric conversion efficiency to absorption rate (SAR) value was the highest. Therefore, a Lu doping concentration of 1% was ultimately chosen for preparing the Lu-doped nanozymes. 0.01 Fe 0.99 Te2 magnetic nanozyme.
[0026] S3: Magnetically triggered thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 Preparation of Te2@SnTe (LFS); In S3, LFS magnetically triggered thermoelectrocatalytic nanozymes were prepared via a one-step cation exchange method, as detailed below: S31: Disperse 0.99 mmol of Fe(acac)3 and 0.01 mmol of Lu(acac)3 in a 100 mL three-necked flask containing 20 mL of OM, and heat from room temperature to 180 °C under magnetic stirring, and maintain at 180 °C for 30 min. S32: Dissolve 3 mmol of Te particles in 5 mL of TOP in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. Maintain the temperature at 300 °C for 60 min. After the reaction is complete, quickly reduce the temperature of the reaction system to 200 °C. S33: Weigh 0.3 mmol SnCl2·2H2O and dissolve it in 4 mL of diethylene glycol. After sonicating it to completely disperse and dissolve, add it to the above mixed solution at 200℃ and react at 200℃ for 30 min by cation exchange method. S34: After the reaction is completed and cooled to room temperature, anhydrous ethanol is added to cause the nanoparticles to precipitate. The nanoparticles are washed three times with cyclohexane and anhydrous ethanol, and centrifuged at 12,000 rpm for 15 min to obtain LFS nanoparticles.
[0027] By adding different proportions of Sn source SnCl2·2H2O, LFS with different magnetocaloric and thermoelectric catalytic properties was investigated.
[0028] Magnetic trigger thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 Characterization of Te2@SnTe: like Figure 5 and Figure 6 As shown, XRD characterization was first used at different reaction temperatures to see if the thermoelectric catalyst SnTe could be obtained via cation exchange. Figure 5 It can be seen that Lu can only be obtained at 200℃. 0.01 Fe 0.99 Te2@SnTe. A series of nanozymes were obtained by setting different Sn source ratios. Through... Figure 6 The b XRD pattern shows that only Sn ≥ 3 mmol can yield Lu through cation exchange. 0.01 Fe 0.99 Te2@SnTe. (via) Figure 5 d. Magnetothermal performance characterization and Figure 6 Based on the magnetic response thermoelectric catalytic performance of af, it can be seen that when Sn = 0.3 mmol, Lu 0.01 Fe 0.99 Te2@SnTe can maintain good magnetocaloric properties and also has excellent pyroelectrocatalytic properties to produce a large amount of ·OH.
[0029] like Figure 7 As shown, the band structure of the two materials was characterized by XPS-VB and UV-Vis diffuse reflectance spectroscopy. The band structure diagrams reveal that the two materials successfully constructed a Z-type heterojunction, which can thermodynamically and kinetically drive the generation of ROS in two narrow-bandgap semiconductors, and achieve high-quality generation in different semiconductors.1 O2 and ·OH.
[0030] S4: Magnetically triggered thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 Preparation of Te2@SnTe-PEI / HA (LFSH); The specific preparation method of the magnetically triggered thermoelectrocatalytic nanozyme LFSH in S4 is as follows: S41: 35mg of Lu 0.01 Fe 0.99 Te2@SnTe was dispersed in 30 mL of cyclohexane, and 3.5 mg of PEI was dispersed in 30 mL of anhydrous ethanol. The two were added dropwise and mixed under ultrasonication. The mixture was stirred overnight in a shaker at 180 rpm. The product was collected by centrifugation, washed three times with ultrapure water, and then redispersed in 30 mL of ultrapure water. S42: Disperse 175 mg of HA in 30 mL of ultrapure water, add the above product aqueous solution dropwise to the HA aqueous solution under ultrasonication, mix and shake in a shaker at 180 rpm for 24 h, collect the product by centrifugation after the end, wash the product three times with ultrapure water, and finally place it in a freeze dryer for freeze drying to obtain LFSH.
[0031] Characterization of magnetically triggered thermoelectrocatalytic nanozyme LFSH: like Figure 8 As shown, through the Zeta potential ( Figure 8 a) It can be seen that Lu 0.01 Fe 0.99 Te2@SnTe carries a negative charge. After potential modification with PEI, it is converted to a positive charge, and then combined with negatively charged hyaluronic acid (HA) via electrostatic adsorption. XRD patterns were observed... Figure 8 b) It can be seen that the modification of PEI / HA does not affect Lu 0.01 Fe 0.99 The crystal structure of Te2@SnTe. (The text appears to be incomplete and contains several grammatical errors. A Figure 8 As shown in c, its hydrated particle size increased slightly by 5 nm compared to before modification. After modification with HA, the nanozyme acquires tumor-targeting ability because HA has the ability to specifically bind to the CD44 receptor on the tumor cell membrane.
[0032] Characterization of the magnetocaloric properties of magnetically triggered thermoelectrocatalytic nanoenzyme LFSH: like Figure 9 and Figure 10 As shown, in order to investigate the magnetic effects of magnetically responsive nanozymes and magnetically triggered thermoelectric nanozymes, such as... Figure 9 The hysteresis loops of the two nanozymes were detected using a vibrating sample magnetometer at room temperature. Lu 0.01Fe 0.99 The saturation magnetization of Te2 reached 35.37 emu / g, and its hysteresis loop indicates good paramagnetic effect. After placing a magnet next to the LFSH solution, it was clearly observed that the nanoparticles were adsorbed onto one side of the magnet after 30 seconds, and the solution became clear and transparent, indicating that it has good magnetic responsiveness.
[0033] The magnetocaloric properties of LFSH (a magnetically triggered thermoelectrocatalytic nanozyme) were comprehensively characterized. The magnetocaloric properties of LFSH were positively correlated with its concentration and magnetic field strength; higher nanozyme concentrations and stronger magnetic field strengths resulted in a stronger magnetocaloric heating capacity. The magnetocaloric cycling stability was tested over 20 minutes under a magnetic field strength of 20 A. Figure 10 As shown in f, the magnetically triggered thermoelectrocatalytic nanozyme exhibits excellent magnetothermal cycling stability after 5 cycles.
[0034] Acoustodynamic performance characterization of magnetically triggered thermoelectrocatalytic nanoenzyme LFSH: like Figure 11 As shown, acoustic-dynamic performance tests on the iron-based nanozyme revealed that the synthesized nanozyme possesses acoustic-dynamic properties. Figure 11 (ab). Compared with the control group, the degradation ability of LF on DPBF increased with time under the influence of US, revealing that magnetic LFNPs have SDT generation capabilities. 1 The ability of O2. By constructing a Z-shaped heterojunction, the recombination rate of electron-hole pairs is greatly reduced, thereby improving the acoustodynamic performance of LFSH. Figure 11 c), and under the action of ΔT provided by AMF, SDT is generated. 1 The ability of O2 has been further enhanced ( Figure 11 d), the corresponding statistical chart of DPBF degradation is shown in Figure 11 In d. The above results are ESR spectra ( Figure 11 f) was also confirmed; under the influence of ΔT provided by AMF, the higher the temperature difference, the greater the generation of… 1 The stronger the O2's ability.
[0035] Thermoelectrocatalytic performance of magnetically triggered thermoelectrocatalytic nanoenzymes LFSH: like Figure 12 As shown, the excellent magnetocaloric cycling stability of LFSH allows its thermoelectric catalytic performance to be triggered by a temperature gradient field. The temperature difference caused by the heat generated through magnetic triggering creates a built-in electric field within SnTe. This electric field, through the Z-shaped heterostructure, further hinders electron-hole pair recombination, ensuring that LFSH exhibits higher thermoelectric catalytic activity and generates more ROS. The thermoelectric properties of the prepared LFSH and SnTe are as follows: Figure 12As shown, the temperature (T) dependent conductivity (σ) of LFSH and SnTe was first measured and recorded within a temperature range of 25℃–105℃. The conductivity of both LFSH and SnTe increases with increasing temperature. Figure 12 (a) indicates that phonons dominate carrier scattering. Figure 12 b shows the Seebeck coefficient (S) as a function of temperature. S increases slowly with increasing temperature, and the S value of the LFSH composite is significantly higher than that of SnTe. This indicates that a Z-shaped heterostructure is formed between the two components. At the same time, due to the high energy barrier of the heterostructure interface, only carriers with relatively high energy can pass through the energy barrier of the heterostructure interface, while low-energy carriers are filtered out, which reduces the carrier concentration. Figure 12 c presents a power factor (PF=S) 2 The curve of σ as a function of temperature shows that LFSH has a larger power factor (PF) value than SnTe due to the decrease in conductivity and the increase in Seebeck coefficient. Furthermore, Figure 12 Figure d shows the curve of thermal conductivity (κ) as a function of temperature, from which it can be seen that LFSH has a low κ value. Due to the high PF value and low κ value, the thermoelectric figure of merit (ZT=S) of both can be calculated using the formula. 2 σ / κ). For example Figure 12 As shown in e, ZT is an important parameter for estimating the properties of thermoelectric materials. Due to the synergistic suppression of κ and σ and the improvement of S, LFSH was observed to have a higher ZT value. Radar chart ( Figure 12 f) Five parameters (σ, S, PF, κ, and ZT) were comprehensively considered to compare the thermoelectric properties of LFSH and SnTe. Overall, LFSH exhibits superior thermoelectric performance compared to SnTe, particularly with a final ZT value that is 1.2 times that of SnTe. In conclusion, the successful construction of the Z-shaped heterostructure ultimately enhances the thermoelectric performance of LFSH.
[0036] like Figure 13 As shown, the pyroelectric current response curves of LF, SnTe, and LFSH under three temperature fluctuations were measured using an electrochemical workstation. In comparison, LFSH exhibited a higher pyroelectric current ( Figure 13 a) further demonstrates that LFSH exhibits the best charge transfer and separation performance. Figure 13 b) Used to verify internal resistance and interfacial charge transfer. In comparison, LFSH exhibits the smallest radius of curvature of the EIS during temperature changes, reflecting its lower internal resistance and faster charge transfer rate. Next, we further investigated the thermoelectrocatalytic ability of LFSH to generate •OH through three temperature difference (ΔT) cycles under the influence of AMF using methylene blue (MB) as a detector. Figure 13As shown in Figure ce, compared with the control group, the characteristic absorption peak of MB in LFSH decreased with increasing cycle number after three ΔT cycles, demonstrating its high ability to generate •OH under ΔT conditions, thus degrading MB. Furthermore, the PEDT performance of LFSH also showed a concentration-dependent effect; the higher the concentration, the more •OH was generated through three ΔT cycles under the action of AMF, and the stronger the degradation ability of MB. Figure 13 As shown in f, the ability of LFSH to generate •OH via PEDT was further demonstrated using ESR and DMPO trapping agents. No •OH was generated in pure water or with LFSH alone without an applied ΔT. However, with an applied ΔT, a typical 1:2:2:1 •OH characteristic peak was observed, and the peak intensity increased with increasing ΔT. The above results are illustrated in the ESR spectrum (…). Figure 14 b) This has also been confirmed. Under the influence of ΔT provided by AMF, the higher the temperature difference, the stronger its ability to generate 1O2.
[0037] POD-Like enzyme activity of magnetically triggered thermoelectrocatalytic nanozyme LFSH: like Figure 14 As shown, in a buffer solution at pH 5.5, LFSH exhibits a characteristic peak at 650 nm for the oxidized TMB state (ox-TMB), indicating that the LFSH nanozyme possesses POD-like enzyme activity under these conditions. Furthermore, we investigated the effects of US and the ΔT provided by AMF (thermoelectrocatalysis) on the POD-like enzyme activity. Figure 14 As can be seen from point a, the accelerated diffusion of reactants in the solution under the influence of ultrasound (US) makes it easier for the reactants to contact the surface of the nanomaterials, thus speeding up the reaction rate. Simultaneously, ultrasound generates cavitation in the liquid, releasing energy and creating localized temperature and pressure, further accelerating the reaction process. Therefore, the POD-like enzyme activity of LFSH nanozymes is further enhanced under the influence of US. Similarly, under the influence of ΔT provided by AMF, the magnetic LFSH nanozymes generate a large amount of heat through the magnetocaloric effect. This heat accelerates intermolecular motion and increases the reaction rate; therefore, the excellent thermoelectric catalysis further enhances the POD-like enzyme activity. Importantly, the combined effect of US and ΔT results in the highest possible POD-like enzyme activity of LFSH.
[0038] LCO-Like enzyme activity of magnetically triggered thermoelectrocatalytic nanozyme LFSH: like Figure 15As shown, the 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) method was used to detect LCO-Like enzyme activity. LFSH exhibits excellent LCO-Like enzyme activity, which can reduce the content of L-Cys in tumor cells and disrupt the redox balance of tumor cells. Figure 15 As shown, LFSH nanozymes can oxidize and consume L-Cys, which not only continuously reduces GSH synthesis but also indirectly amplifies the effect of ROS. Under the influence of US and ΔT, the POD-like enzyme activity of LFSH is further enhanced, as shown in the corresponding statistical graphs ( Figure 15 e) It can be seen that under the combined effects of US and ΔT, the LCO-Like enzyme activity of LFSH nanozyme reaches its maximum.
[0039] NADPH oxidase (Nox-like) activity of magnetically triggered thermoelectrocatalytic nanozyme LFSH: like Figure 16 As shown, the characteristic ultraviolet absorption peak of NADPH is at 340 nm, and that of NADP... + The characteristic ultraviolet absorption peak is at 260 nm. When the nanozyme has NADPH oxidase activity, it can oxidize NADPH into NADP. + The UV absorption spectrum shows a decrease in the absorption peak at 340 nm and an increase in the absorption peak at 260 nm. Figure 16 It is known that the magnetically triggered thermoelectrocatalytic nanozyme LFSH has NADPH oxidase activity, and under the dual effects of US and ΔT, the Nox-like enzyme activity of LFSH nanozyme reaches its highest level.
[0040] LDH-like enzyme activity of magnetically triggered thermoelectrocatalyzed nanozyme LFSH: like Figure 17 As shown, the LDH-like activity of the magnetically triggered thermoelectrocatalyzed nanozyme LFSH was detected using an L-lactic acid kit. Figure 17 It is known that LFSH possesses LDH-like activity, and the consumption of L-lactic acid increases with increasing concentration. The LDH-like enzyme activity of SnTe and LFSH nanozymes was detected using an L-lactic acid assay kit (WST-8 method). Encouragingly, both SnTe and LFSH exhibit LDH-like enzyme activity, such as... Figure 17 As shown in Figure a, compared with PBS and simple LFNPs, the LFSH nanozyme containing the SnTe component achieved the consumption of lactate molecules, and the lactate content was further reduced upon stimulation with US and ΔT. Furthermore, the activity of LDH-like enzymes also exhibited a concentration-dependent effect; the higher the concentration of the LFSH nanozyme, the greater the consumption of lactate. Figure 17 b).
[0041] S5: In vitro antitumor effect of magnetically triggered thermoelectrocatalytic nanozyme LFSH.
[0042] S5 also includes: Biosafety of magnetically triggered thermoelectrocatalytic nanoenzymes LFSH; like Figure 18 As shown, experiments were conducted using mouse fibroblasts (L929), mouse brain endothelial cell line (bEnd.3), and mouse embryonic fibroblasts (3T3). Figure 18 As shown in the ac, the cell viability of LFSH was greater than 80% at a final concentration below 400 μg / mL, indicating that it had good biosafety.
[0043] Evaluation of the uptake capacity of GL261 cells of magnetically triggered thermoelectrocatalytic nanozyme LFSH; like Figure 19 As shown, the cellular uptake of nanoparticles by GL261 cells was investigated using FITC-labeled LFSH nanozymes. Since the nanozyme surface is coated with a layer of HA molecules that can bind to a large number of CD44 receptors on the surface of GL261 cells, HA molecules were added beforehand during cell culture to block the binding of NFSH to the CD44 antibody. The test results are as follows. Figure 19 As shown, no obvious green fluorescence signal was observed in the HA pretreatment group within 1–6 hours, while a significant FITC fluorescence signal was observed in the untreated group. This indicates that the introduction of HA enhances the cellular uptake of NFSH by GL261 cells. Furthermore, in the magnet-treated group, a significant FITC green fluorescence signal was observed as early as 2 hours, and the signal intensity significantly increased over time. Within the same time frame, the fluorescence signal intensity in the magnet-treated group was much higher than that in the untreated group, indicating that nanozymes are more easily taken up by cancer cells under the influence of an external magnet. The combined effect of magnetic drive and HA molecular targeting can help guide these nanozymes to specific areas of the body, improving the targeting efficiency of nanomedicines and facilitating their application in tumor therapy.
[0044] Evaluation of magnetically driven BBB penetration of LFSH nanozymes; like Figure 20 As shown, an in vitro BBB model was constructed using bEnd.3 cells to assess the BBB penetration ability of LFSH. Transendothelial resistance (TEER) measurements showed a ΔTEER value exceeding 180 Ω·cm², confirming the successful establishment of a tight endothelial monolayer. Fluorescence signal intensity at different time points in lower chamber GL261 cells was captured using CLSM. Figure 20Without a static magnetic field and AMF, almost no fluorescence signal was observed within 1–6 hours. Conversely, under AMF stimulation, the magnetocaloric effect of LFSH temporarily disrupted the BBB, resulting in a strong fluorescence signal intensity visible after 2 hours. The magnetic drive effect of an external magnet further accelerated the uptake of LFSH. These results demonstrate that LFSH nanozymes can effectively penetrate the BBB under the drive of dual magnetic fields.
[0045] Evaluation of the killing ability of GL261 cells.
[0046] like Figure 21 - Figure 22 As shown, the killing effect of nanozymes on GL261 cells was evaluated under different stimulation conditions. Based on previous research on the performance of this nanozyme, (G1) PBS; (G2) US+AMF; (G3) LFSH; (G4) LFSH+US; (G5) LFSH+AMF; and (G6) LFSH+US+AMF were designed. Figure 21 It can be seen that in the G6 group of combined treatment, the tumor cell killing rate was about 90%.
[0047] The level of ROS production in GL261 cells under different stimulation conditions was detected using the DCFH-DA fluorescent probe. DCFH-DA can bind to reactive oxygen species in cells to produce green fluorescent DCF. Figure 22 As shown, under the dual stimulation of US and AMF, magnetically triggered thermoelectrocatalytic nanozymes can generate ROS storms, thereby killing tumor cells.
[0048] S6: In vivo antitumor effect of magnetically triggered thermoelectrocatalytic nanozyme LFSH.
[0049] like Figure 23 As shown, the in vivo antitumor effects of LFSH are as follows: An orthotopic glioblastoma model was successfully constructed by in situ injection of GL261-LUC tumor cells into the brain region of C57BL / 6J mice around 7 weeks old. The nanozyme was administered via tail vein, and treatment was performed with ultrasound stimulation (1MHz, 10min, 50% duty cycle) and magnetothermal stimulation (f=498KHz, 1.6mT). To monitor the treatment effect in tumor-bearing mice during the treatment cycle, D-fluorescein potassium salt was injected intraperitoneally and observed using an animal in vivo imaging system. The groups are as follows: (G1) PBS+US+AMF; (G2) LFSH; (G3) LFSH+Magnet; (G4) LFSH+US+Magnet; (G5) LFSH+AMF+Magnet; (G6) LFSH+US+AMF+Magnet.
[0050] Tumor progression was monitored by bioluminescence imaging on days 0, 5, 10, and 14, such as... Figure 23 As shown, compared with the control group, the bioluminescent signals of other groups decreased to varying degrees as treatment progressed, indicating different levels of tumor treatment efficacy. Compared with group G2, group G3 showed a corresponding increase in tumor inhibition. This is because, under the influence of an external static magnet in the mouse brain, magnetic LFSH nanozymes could accumulate more extensively at the tumor site, enhancing the anti-tumor effect. In groups G4 and G5, US and AMF stimulation further enhanced the anti-tumor effect. Particularly in group G6, where both US and AMF stimulation were administered simultaneously, there was no significant increase in fluorescence signal intensity, demonstrating that LFSH nanozymes have a significant inhibitory effect on tumors under US and AMF stimulation.
[0051] An application of a magnetically triggered thermoelectrocatalytic nanozyme, utilizing the multiple enzyme activities of LFSH nanozymes, for the treatment of glioma.
[0052] The above description is merely a preferred embodiment of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention. Structures, devices, and operating methods not specifically described or explained in this invention are implemented according to conventional methods in the art unless otherwise specified or limited.
Claims
1. A method for preparing magnetically triggered thermoelectrocatalytic nanozymes, characterized in that: The preparation method includes the following steps: S1: Preparation of magnetic nanozyme FeTe2; S2: Rare earth element Lu-doped magnetic nanoenzyme Lu x Fe 1-x Preparation of Te2; S3: Magnetically triggered thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 Preparation of Te2@SnTe; S4: Magnetically triggered thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 Preparation of Te2@SnTe-PEI / HA; S5: Magnetically triggered thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 In vitro antitumor effects of Te2@SnTe-PEI / HA; S6: Magnetically triggered thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 In vivo antitumor effects of Te2@SnTe-PEI / HA.
2. The method for preparing a magnetically triggered thermoelectrocatalytic nanozyme according to claim 1, characterized in that: The specific preparation method in S1 is as follows: S11: Disperse 1.0 mmol of Fe(acac)3 in a 100 mL three-necked flask containing 20 mL of oleylamine, and heat it from room temperature to 180 °C under magnetic stirring, and keep it at 180 °C for 30 min. S12: Dissolve 3 mmol of Te particles in 5 mL of trioctylphosphine in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the above three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. S13: Maintain at 300℃ for 60 min. After the reaction is completed and cooled to room temperature, add anhydrous ethanol to cause the nanoparticles to precipitate. Wash the nanoparticles three times with cyclohexane and anhydrous ethanol. Centrifuge at 12000 rpm for 15 min to obtain FeTe2 nanoparticles.
3. The method for preparing a magnetically triggered thermoelectrocatalytic nanozyme according to claim 1, characterized in that: Magnetic nanozyme Lu in S2 x Fe 1-x The specific method for preparing Te2 is as follows: S21: Magnetic nanozymes with Lu doping levels of 0.5%, 1.0%, 1.5%, and 2.0% were prepared, respectively. x Fe 1-x Te2; S22: Disperse 1-x mmol of Fe(acac)3 and x mmol of Lu(acac)3 in a 100 mL three-necked flask containing 20 mL of OM, and heat from room temperature to 180 °C under magnetic stirring, and maintain at 180 °C for 30 min. S23: Dissolve 3 mmol of Te particles in 5 mL of TOP in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. S24: Maintain the reaction at 300℃ for 60 min. After cooling to room temperature, add anhydrous ethanol to cause the nanoparticles to precipitate. Wash the nanoparticles three times with cyclohexane and anhydrous ethanol, and centrifuge at 12000 rpm for 15 min to obtain Lu. 0.01 Fe 0.99 Te2 nanoparticles.
4. The method for preparing a magnetically triggered thermoelectrocatalytic nanozyme according to claim 1, characterized in that: In step S3, magnetically triggered thermoelectrocatalytic nanozyme Lu is prepared via a one-step cation exchange method. 0.01 Fe 0.99 Te2@SnTe, as detailed below: S31: Disperse 0.99 mmol of Fe(acac)3 and 0.01 mmol of Lu(acac)3 in a 100 mL three-necked flask containing 20 mL of OM, and heat from room temperature to 180 °C under magnetic stirring, and maintain at 180 °C for 30 min. S32: Dissolve 3 mmol of Te particles in 5 mL of TOP in an oil bath at 150 °C to form a yellow transparent solution. Then add the solution dropwise to the three-necked flask at 180 °C. Continue to heat the mixed solution to 300 °C at a heating rate of 10 °C / min. Maintain the temperature at 300 °C for 60 min. After the reaction is complete, quickly reduce the temperature of the reaction system to 200 °C. S33: Weigh 0.3 mmol SnCl2·2H2O and dissolve it in 4 mL of diethylene glycol. After sonicating it to completely disperse and dissolve, add it to the above mixed solution at 200℃ and react at 200℃ for 30 min by cation exchange method. S34: After the reaction is complete and cooled to room temperature, anhydrous ethanol is added to cause the nanoparticles to precipitate. The nanoparticles are then washed three times with cyclohexane and anhydrous ethanol, and centrifuged at 12,000 rpm for 15 min to obtain Lu. 0.01 Fe 0.99 Te2@SnTe nanozyme.
5. The method for preparing a magnetically triggered thermoelectrocatalytic nanozyme according to claim 4, characterized in that: By adding different proportions of Sn source SnCl2·2H2O, the study was conducted on Lu 0.01 Fe 0.99 Different magnetocaloric and thermoelectric catalytic properties of Te2@SnTe.
6. The method for preparing a magnetically triggered thermoelectrocatalytic nanozyme according to claim 1, characterized in that: The magnetically triggered thermoelectrocatalytic nanoenzyme Lu in S4 0.01 Fe 0.99 The specific preparation method of Te2@SnTe-PEI / HA is as follows: S41: 35mg of Lu 0.01 Fe 0.99 Te2@SnTe was dispersed in 30 mL of cyclohexane, and 3.5 mg of PEI was dispersed in 30 mL of anhydrous ethanol. The two were added dropwise and mixed under ultrasonication. The mixture was stirred overnight in a shaker at 180 rpm. The product was collected by centrifugation, washed three times with ultrapure water, and then redispersed in 30 mL of ultrapure water. S42: Disperse 175 mg of HA in 30 mL of ultrapure water. Add the above product aqueous solution dropwise to the HA aqueous solution under ultrasonication. Mix and shake in a shaker at 180 rpm for 24 h. After the mixture is removed, collect the product by centrifugation, wash the product three times with ultrapure water, and finally freeze-dry it to obtain Lu. 0.01 Fe 0.99 Te2@SnTe-PEI / HA.
7. The method for preparing a magnetically triggered thermoelectrocatalytic nanozyme according to claim 1, characterized in that: S5 also includes: Magnetic trigger thermoelectrocatalytic nanoenzyme Lu 0.01 Fe 0.99 Te2@SnTe-PEI / HA biocompatibility; GL261 cells for magnetically triggered thermoelectrocatalytic nanoenzymes Lu 0.01 Fe 0.99 Assessment of Te2@SnTe-PEI / HA uptake capacity; Lu 0.01 Fe 0.99 Evaluation of magnetically driven BBB penetration of Te2@SnTe-PEI / HA nanozymes; Lu 0.01 Fe 0.99 Evaluation of the killing ability of Te2@SnTe-PEI / HA nanozymes against GL261 cells.
8. The method for preparing a magnetically triggered thermoelectrocatalytic nanozyme according to claim 1, characterized in that: In S6, Lu 0.01 Fe 0.99 The specific in vivo antitumor effects of Te2@SnTe-PEI / HA are as follows: An in situ glioblastoma model was successfully constructed by injecting GL261-LUC tumor cells into the brain region of C57BL / 6J mice at approximately 7 weeks of age. The nanozyme was administered via tail vein, and ultrasound stimulation and magnetothermal therapy were applied. To monitor the treatment effect in tumor-bearing mice during the treatment cycle, D-fluorescein potassium salt was injected intraperitoneally and observed using an animal in vivo imaging system. The groups are as follows: (G1) PBS+US+AMF; (G2) LFSH; (G3) LFSH+Magnet; (G4) LFSH+US+Magnet; (G5) LFSH+AMF+Magnet; (G6) LFSH+US+AMF+Magnet.
9. An application of a magnetically triggered thermoelectrocatalytic nanozyme, characterized in that: The multiple enzyme activities of LFSH nanozymes are utilized for the treatment of glioma.