Tannic acid modified tungsten disulfide nanosheet and application thereof in treatment of acetaminophen acute liver injury

Abstract

The invention discloses a tannic acid modified tungsten disulfide nanosheet and application thereof in treatment of acetaminophen acute liver injury, the nanosheet takes a tungsten disulfide nanosheet as a core, and the surface of the tungsten disulfide nanosheet is modified with electronegative tannic acid. The nanosheet disclosed by the invention has good stability and biocompatibility, can be used for preparing a nano-drug for treating acetaminophen acute liver injury, and specifically targets and removes active oxygen at a liver injury part through an electrostatic adsorption effect, so that inflammatory response is inhibited, and symptoms caused by the acute liver injury are effectively relieved.

Description

Technical Field

[0001] The present invention belongs to the field of nanomaterial preparation and biomedicine, and specifically relates to a tannic acid-modified tungsten disulfide nanosheet and its application in treating acute liver injury caused by acetaminophen. Background Art

[0002] Acetaminophen (APAP) is a common over-the-counter analgesic and fever reducer widely used to relieve mild to moderate pain and fever. However, overdose of acetaminophen can induce hepatocellular toxicity, leading to acute liver injury (AILI).

[0003] 85–90% of APAP is metabolized by UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) into non-toxic metabolites, which are subsequently excreted in the urine. The remaining APAP is primarily metabolized by cytochrome P450 enzymes (CYs), producing N-acetyl-p-benzoquinoneimine (NAPQI), a compound with significant cytotoxicity. Normally, NAPQI binds to the sulfhydryl group of cysteine ​​residues in glutathione (GSH) to form NAPQI-GSH conjugates. These conjugates are initially excreted in the bile, then transported to the kidneys and other organs and excreted in the urine. However, in the case of APAP overdose, the excessive production of NAPQI depletes GSH stores, leading to excessive concentrations of harmful reactive oxygen and nitrogen species (RONS). This process triggers mitochondrial oxidative stress and ultimately leads to liver damage. Furthermore, the pathological process of AILI involves the interaction of oxidative stress with inflammatory responses and cell apoptosis. In addition to RONS clearance, factors such as liver targeting and the ability to regulate specific signaling pathways have a significant impact on the therapeutic efficacy of AILI. Therefore, targeting the accumulation of RONS at sites of liver damage and efficiently clearing RONS may be a potential effective strategy for treating AILI.

[0004] In recent years, the application of nanomaterials in the biomedical field has become increasingly widespread. Tungsten disulfide (WS2), an emerging two-dimensional nanomaterial, has shown significant potential for anti-inflammatory applications due to its unique physicochemical properties. Studies have shown that WS2 nanoflowers can alleviate cell apoptosis and lipid peroxidation by scavenging RONS, thereby exerting anti-inflammatory effects in a model of acute liver injury induced by carbon tetrachloride. However, their antioxidant activity is limited by their low surface area and lack of liver targeting, limiting their potential for the treatment of liver-related diseases. Currently, there is no published data on the use of WS2 in the treatment of APAP-induced AILI. WS2 nanosheets, on the other hand, have a higher surface area, providing more active sites for RONS scavenging. Tannic acid, a natural polyphenol compound extracted from plants, is characterized by its complex structure, strong reducing properties, high free radical scavenging activity, and diverse derivatization reactivity. Its low toxicity and significant anti-inflammatory and antioxidant properties have attracted considerable attention in the biomedical field. Tannic acid can effectively alleviate inflammation and protect cells from oxidative stress by inhibiting the expression of inflammatory factors (such as TNF-α) and scavenging RONS. Currently, there are no reports on the use of WS2 or tannic acid in the treatment of AILI. Therefore, developing a novel nanomaterial that combines the advantages of both to achieve more efficient and specific treatment has become a pressing technical challenge in this field. Summary of the Invention

[0005] To address the limitations of conventional drugs currently used in clinical practice, such as their scope of application, timing of use, and potential side effects, the present invention provides a tannic acid-modified tungsten disulfide nanosheet and its application in treating acute liver injury caused by acetaminophen. Tannic acid-modified tungsten disulfide nanosheets are designed and synthesized to have high-efficiency reactive oxygen species scavenging capabilities, and their unique physicochemical properties are utilized to achieve targeted delivery to the site of liver injury. By specifically scavenging excess RONS, oxidative stress is significantly reduced, and liver cell repair and regeneration are promoted, thereby effectively treating APAP-induced AILI. This provides a new and highly effective treatment strategy for acute liver injury.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The present invention first discloses a tannic acid-modified tungsten disulfide nanosheet for treating acute liver damage caused by acetaminophen. The tannic acid-modified tungsten disulfide nanosheet is characterized in that: the tannic acid-modified tungsten disulfide nanosheet is composed of a tungsten disulfide nanosheet as the core, and the surface of the tungsten disulfide nanosheet is modified with negatively charged tannic acid. The preparation method includes the following steps:

[0008] Tungsten disulfide powder frozen with liquid nitrogen is added to an aqueous solution containing tannic acid, and the mixture is ultrasonically crushed and centrifuged to obtain a supernatant. The obtained supernatant is centrifuged, washed, and freeze-dried to obtain tannic acid-modified tungsten disulfide nanosheets.

[0009] Furthermore, the mass ratio of tannic acid to tungsten disulfide nanosheets is 1 to 9:1.

[0010] Furthermore, the ultrasound is performed alternately by probe ultrasound and room temperature water bath ultrasound, the power of the probe ultrasound is 80-600W, the total time is 2-9h, and the power of the room temperature water bath ultrasound is 10-200W, the total time is 2-9h.

[0011] The tannic acid modified tungsten disulfide nanosheets of the present invention have the following characteristics: good biosafety at the cellular and animal levels; the ability to scavenge reactive oxygen and reactive nitrogen; the surface carries a negative charge, which can specifically target the site of liver damage, thereby alleviating oxidative stress reactions and protecting cells and tissues from oxidative damage, thereby achieving the effect of treating acute liver damage caused by acetaminophen. The mechanism of the tannic acid modified tungsten disulfide nanosheets of the present invention for treating acute liver damage is: utilizing the unique physical and chemical properties of tannic acid modified tungsten disulfide nanosheets to achieve targeted enrichment at the site of liver damage, thereby improving the effect of treating acute liver damage. Tannic acid modified tungsten disulfide nanosheets have W on their surface. 4+ To W 6+ The valence state transition and S 2- The synergistic oxidative reaction mediates the redox reaction to efficiently remove RONS, thereby effectively alleviating oxidative stress damage and reducing hepatocyte apoptosis. After tail vein injection, tannic acid-modified tungsten disulfide nanosheets improved APAP-induced acute liver injury.

[0012] The beneficial effects of the present invention are embodied in:

[0013] 1. The tannic acid modified tungsten disulfide nanosheets of the present invention have good antioxidant properties, biocompatibility and stability. Tannic acid can effectively reduce inflammatory reactions and protect cells from oxidative stress damage by inhibiting the expression of inflammatory factors. 4+ To W 6+ The valence state transition and S 2- The synergistic oxidation reaction mediates the redox reaction and efficiently removes RONS; at the same time, the two-dimensional tungsten disulfide nanosheets can achieve a targeted enrichment effect at the site of liver damage through surface charge.

[0014] 2. The two-dimensional tungsten disulfide nanosheets of the present invention are used to treat acute liver injury caused by acetaminophen, which significantly improves the anti-inflammatory properties of the nanomedicine and significantly reduces the dosage.

[0015] 3. The preparation process of the tannic acid modified tungsten disulfide nanosheets of the present invention is simple, the conditions are mild, and it is possible to produce on a large scale, and has the potential for industrial and practical applications.

[0016] 4. The materials used in the present invention have good biocompatibility, no direct or indirect toxic effects on mice, and no potential toxicity.

[0017] 5. The two-dimensional nanosheets of the present invention have good dispersibility and stability, which is conducive to clinical use. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Schematic diagram of the synthesis of the present invention.

[0019] Figure 2 This is a transmission electron microscope image of the WS2@TA nanosheets prepared in Example 1.

[0020] Figure 3 This is an atomic force microscope image of the WS2@TA nanosheets prepared in Example 1.

[0021] Figure 4 Zeta potential diagram of WS2@TA nanosheets prepared in Example 1.

[0022] Figure 5 The XPS spectra of WS2@TA nanosheets prepared in Example 1, where (a) is the XPS spectrum of WS2@TA, and (b) to (e) are the spectra of C, O, S, and W elements in WS2@TA, respectively.

[0023] Figure 6 The particle size diagram of WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1.

[0024] Figure 7 XRD patterns of WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1.

[0025] Figure 8 Diagram of the in vitro scavenging of DPPH (1,1-diphenyl-2-picrylhydrazyl) free radicals by WS2@TA nanosheets prepared in Example 1 and pure WS2 nanosheets.

[0026] Figure 9 Figure 3 shows the in vitro scavenging of ABTS (2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) free radicals by WS2@TA nanosheets prepared in Example 1 and pure WS2 nanosheets.

[0027] Figure 10 Figure 3 shows the in vitro scavenging of hydroxyl radicals by WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1.

[0028] Figure 11Cell reactive oxygen species staining images of WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1.

[0029] Figure 12 This is a graph showing the biocompatibility of WS2@TA nanosheets prepared in Example 1 at different concentrations.

[0030] Figure 13 Cell AM / PI live / dead staining images of WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1.

[0031] Figure 14 This is the distribution diagram of WS2@TA nanosheets prepared in Example 1 in mice at different time points.

[0032] Figure 15 AST and ALT statistical graphs of the WS2@TA nanosheets prepared in Example 1 in treating APAP-induced acute liver injury in mice.

[0033] Figure 16 This is a graph showing the survival rate of mice with APAP-induced acute liver injury treated with WS2@TA nanosheets prepared in Example 1. DETAILED DESCRIPTION

[0034] To make the above-mentioned objects, features, and advantages of the present invention more clearly understood, the following detailed description of the specific embodiments of the present invention is provided in conjunction with the following embodiments. The following is merely an example and illustration of the concept of the present invention. Any modification, supplement, or substitution of the described specific embodiments by a person skilled in the art, as long as it does not deviate from the concept of the invention or exceed the scope defined by the claims, shall fall within the scope of protection of the present invention.

[0035] Example 1

[0036] In this example, tannic acid-modified tungsten disulfide nanosheets were prepared as follows:

[0037] 0.6g of tannic acid (TA) was ultrasonically dissolved in 25mL of deoxygenated water. Then, 200mg of tungsten disulfide powder, which had been ultra-chilled in liquid nitrogen for 1h, was added. Probe sonication (480W) and room temperature water bath sonication (150W) were performed alternately for 0.5h, for a total of 4h. After sonication, the solution was centrifuged at 3000rpm for 20min, and the supernatant was collected. The supernatant was then centrifuged at 13000rpm for 20min, and the precipitate was collected and washed twice with water to obtain tannic acid-modified tungsten disulfide nanosheets, designated WS2@TA nanosheets, which were stored at 4°C.

[0038] Figure 2This is a transmission electron micrograph of the WS2@TA nanosheets obtained in this example. Characterization was performed by dropping an aqueous dispersion of the WS2@TA nanosheets onto a copper transmission electron microscope grid, allowing it to dry, and then observing it under a transmission electron microscope. The image shows that the nanosheets have a diameter of 150 to 200 nm.

[0039] Figure 3 This is an atomic force microscope image of the WS2@TA nanosheets obtained in this example. Characterization was performed by dropping an aqueous dispersion of WS2@TA nanosheets onto a mica sheet, allowing it to dry, and then observing it under an atomic force microscope. The image shows that the nanosheets are 4 to 8 nm thick.

[0040] Figure 4 This is a zeta potential plot of the WS2@TA nanosheets obtained in this example. Characterization was performed by adding 700 μL of an aqueous dispersion of WS2@TA nanosheets to a zeta potential sample cell and measuring the zeta potential using a NanoZS90 Malvern particle size analyzer. The plot shows that the zeta potential of pure two-dimensional tungsten disulfide nanosheets is -13 mV. After modification with tannic acid, the zeta potential decreases to -16 mV, demonstrating the successful loading of tannic acid molecules onto the surface of the two-dimensional tungsten disulfide nanosheets.

[0041] Figure 5 This is the XPS graph of the WS2@TA nanosheets obtained in this example. The characterization method is: the WS2@TA nanosheets are freeze-dried into powder using a freeze dryer, and the XPS graph is obtained using an X-ray photoelectron spectrometer. It can be seen from the figure that the surface of the WS2@TA nanosheets contains C, O, W, and S elements, and the main valence states of tungsten and sulfur are +4 and -2, respectively, indicating that tannic acid is successfully modified on the surface of the tungsten disulfide nanosheets, and the tungsten disulfide nanosheets have potential reducing ability.

[0042] Figure 6 This is a diagram of the hydrated particle size of the WS2@TA nanosheets obtained in this example. The characterization method is: the synthesized WS2@TA nanosheet solution is centrifuged and washed with water twice, then dispersed in an aqueous solution, and its particle size is measured using a particle size instrument. It can be seen from the figure that the diameter of the nanosheet is about 150nm.

[0043] Figure 7 The XRD spectra of the WS2@TA nanosheets obtained in this example are compared with those of pure WS2 nanosheets. The characterization method is as follows: the nanosheet solution is freeze-dried into powder using a freeze dryer, and its spectrum is measured using an X-ray diffractometer and compared with a standard tungsten disulfide XRD card. It is found that the crystal characteristics after synthesis have not changed.

[0044] Figure 8Figure 1 shows the in vitro scavenging of DPPH (1,1-diphenyl-2-picrylhydrazyl) free radicals by the WS2@TA nanosheets and pure WS2 nanosheets obtained in this example. DPPH is a very stable nitrogen-centered free radical that dissolves in ethanol, exhibits a purple color, and has a characteristic UV absorption peak at 519 nm. The DPPH scavenging effect was determined by detecting the UV absorption peak at 519 nm after incubation of the material with DPPH. The specific experimental steps were as follows: 1 mg of DPPH was dissolved in 20 mL of anhydrous ethanol and completely dissolved by sonication. WS2@TA nanosheets and pure WS2 nanosheets of varying concentrations (their concentrations were adjusted by adjusting the mass of the nanosheets during preparation) were then added and reacted with DPPH for 30 minutes (the final concentrations of the nanosheets in the system were 0, 15, 30, 60, or 120 μg / mL, respectively). DPPH + water was used as a positive control. Finally, the mixture was centrifuged at 15,000 rpm for 10 minutes, and the supernatant was measured for UV absorption at 519 nm. As can be seen from the figure, WS2@TA nanosheets show significant advantages in scavenging DPPH free radicals. The system containing 120 μg / mL WS2@TA nanosheets has an ability to scavenge DPPH of about 70%.

[0045] Figure 9 Figure 2 shows the in vitro scavenging of ABTS (2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) free radicals by the WS2@TA nanosheets obtained in this example and pure WS2 nanosheets. ABTS is oxidized by an oxidant (such as potassium persulfate) to generate a stable blue-green ABTS. ·+ Free radicals. After adding the sample to be tested, the antioxidant components in the sample will react with ABTS ·+ The free radicals react, causing the solution to fade. The effect of scavenging ABTS can be detected by measuring the change in absorbance at 734nm with a spectrophotometer. The specific experimental steps are as follows: Weigh 4.5mg ABTS, dissolve it in 1.2mL ultrapure water, and shake it thoroughly with a vortex mixer until it is completely dissolved. Take another 1.5mg potassium persulfate, dissolve it in 2.2mL ultrapure water, and shake it thoroughly. Mix the two solutions and react them at room temperature in the dark for 12 hours to generate stable ABTS. ·+ After the reaction is completed, dilute the working solution 30-40 times to adjust to A 734In the range of 0.7-0.8. Different concentrations of WS2@TA nanosheets or pure WS2 nanosheets (their concentration was adjusted by adjusting the mass of the nanosheets during preparation) were added to the ABTS working solution to react for 30 minutes (the final concentration of the nanosheets in the system was 0, 1.9, 3.8, 7.5 or 15 μg / mL), and ABTS+water was set as a positive control. Finally, centrifugation was performed at 15,000 rpm for 10 minutes, and the supernatant was taken to measure the ultraviolet absorption at 734 nm. As can be seen from the figure, the effect of WS2@TA nanosheets in scavenging ABTS free radicals is significantly stronger than that of pure WS2 nanosheets. The system containing 15 μg / mL of WS2@TA nanosheets has an ABTS scavenging ability of about 95%.

[0046] Figure 10 Figure 1 shows the in vitro scavenging of hydroxyl radicals by WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1. The salicylic acid method generates hydroxyl radicals via the Fenton reaction. Hydroxyl radicals react with salicylic acid to produce 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid, products with characteristic absorption peaks at 510 nm. The hydroxyl radical scavenging ability of a sample can be assessed by the degree of inhibition of this reaction. The specific experimental steps are: 0.1 mol / L ferrous sulfate and aqueous hydrogen peroxide solutions are prepared, followed by a 0.1 mol / L salicylic acid ethanol solution. The ferrous sulfate and hydrogen peroxide solutions are mixed uniformly and reacted for 10 minutes to generate hydroxyl radicals. WS2@TA nanosheets or pure WS2 nanosheets of varying concentrations (their concentration was adjusted by adjusting the mass of the nanosheets during preparation) are then added to react with the hydroxyl radicals for 1 hour (the final concentration of the nanosheets in the system is 0, 30, 60, 120, or 240 μg / mL, respectively). After the reaction is complete, salicylic acid is added to the reaction system, mixed thoroughly, and allowed to react for 10 minutes. Finally, the mixture was centrifuged at 15,000 rpm for 10 minutes, and the supernatant was measured for UV absorption at 510 nm. As can be seen from the figure, compared with pure WS2 nanosheets, WS2@TA nanosheets have a significant advantage in scavenging hydroxyl radicals. The system containing 240 μg / mL WS2@TA nanosheets has an ABTS scavenging capacity of approximately 80%.

[0047] Figure 11Figure 2 shows the cell reactive oxygen species staining of WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1. The specific experimental steps are as follows: serum-free 1640 culture medium was used to prepare the following different groups of materials: Control (fresh culture medium); 1mM H2O2; 200μg / mL WS2@TA; 1mM H2O2+200μg / mL WS2@TA; 4μg / mL NAC; 1mM H2O2+4μg / mL NAC (clinical drug N-acetylcysteine). In order to verify the scavenging effect of two-dimensional WS2@TA nanosheets on intracellular reactive oxygen species, 100μL (1×10 5 ) and incubated for 24 hours. The supernatant was aspirated, and 100 μL of the prepared solution was added to each well, followed by incubation for 4 hours. After the incubation period, the supernatant was aspirated, the cells were washed three times with PBS, and a 10 μM DCFH-DA staining solution prepared in PBS was added to each well. The cells were incubated at 37°C in the dark for 30 minutes, washed three times with PBS, and photographed under a fluorescence microscope. As can be seen in the figure, the H2O2 + 200 μg / mL WS2@TA group showed no significant green fluorescence, indicating a strong ability to scavenge intracellular reactive oxygen species.

[0048] Figure 12 The biocompatibility diagram of WS2@TA nanosheets prepared in Example 1 at different concentrations. The specific experimental steps are: dilute the WS2@TA nanosheet dispersion to 25μg / mL, 50μg / mL, 100μg / mL, 200μg / mL, and 400μg / mL, and mix 0.2mL of the above solutions with different concentrations with 0.2mL of treated blood (500μL fresh blood is added to 4.5mL of normal saline and centrifuged and washed 5 to 8 times at a centrifugal speed of 3000rpm and a centrifugal time of 10min. After the blood supernatant is clear and transparent, the supernatant is discarded and the volume is fixed to 5mL with normal saline) and 0.6mL of normal saline, incubate at 37℃ for 4h, and then centrifuge at 3000rpm for 10min. The supernatant is aspirated to measure OD 541 nm The absorbance value at 10° was used to calculate the hemolysis rate. The figure shows that the hemolysis rate of WS2@TA nanosheets with different concentrations is less than 10%, indicating that the material has good biocompatibility.

[0049] Figure 13Figure 1 shows the cell AM / PI live / death staining of the WS2@TA nanosheets and pure WS2 nanosheets prepared in Example 1. The specific experimental steps were: serum-free 1640 medium was used to prepare the following different groups of materials: Control (fresh medium); 1mM H2O2; 200μg / mL WS2@TA; 1mM H2O2 + 200μg / mL WS2@TA; 4μg / mL WS2; 1mM H2O2 + 4μg / mL WS2. After incubating AML12 cells for 24 hours, the supernatant was aspirated and washed once with PBS. The above solutions were then added to the well plate in sequence and incubated for 24 hours. After incubation, the culture medium was aspirated, the cells were washed once with PBS, and 300μL of dye (12μL of Calcein AM (calcein acetoxymethyl ester) and 4μL of Propidium Iodide (PI) were mixed and added to 4mL of PBS) and incubated at 37°C in the dark for 20 minutes. Fluorescence microscopy was then used to photograph the cells. As can be seen from the figure, the red fluorescence of the 1 mM H2O2 + 200 μg / mL WS2@TA treatment group is negligible, indicating that WS2@TA can protect normal hepatocytes from the threat of H2O2.

[0050] Figure 14 The distribution of WS2@TA nanosheets prepared in Example 1 in mice at different time points. The specific experimental steps were: Cy5.5-labeled WS2@TA was synthesized by mixing 0.01 mg of Cy5.5 dye with 1 mg of WS2@TA for 12 hours, centrifuging at 13,000 rpm for 20 minutes, collecting the precipitate, washing it twice with water, and centrifuging it at 15,000 rpm for 10 minutes. After fasting for 16 hours, C57 mice were intraperitoneally injected with APAP (300 mg / kg) to establish an AILI model. Healthy mice served as the control group. WS2@TA was administered intravenously to AILI and healthy mice, respectively. Heart, liver, spleen, lung, and kidney samples were collected at 2, 6, 12, and 24 hours, and the fluorescence signal was observed in the dark. As can be seen from the figure, the concentration of WS2@TA in the liver reached a peak 6 hours after intravenous injection. After 24 hours, WS2@TA was essentially metabolized. Furthermore, in the AILI model, WS2@TA demonstrated significant targeted enrichment in the liver.

[0051] Figure 15Figure 1 shows the ALT and AST statistical results of the WS2@TA nanosheets prepared in Example 1 in treating APAP-induced acute liver injury in mice. The specific experimental steps were as follows: healthy mice were randomly divided into 7 groups (n=5): (1) PBS+water, (2) PBS+APAP, (3) 300mg / kg NAC+APAP, (4) 2.5mg / kg WS2+4%APAP, (5) 2.5mg / kg WS2@TA+APAP, (6) 5mg / kg WS2@TA+APAP and (6) 10mg / kg WS2@TA+APAP. After fasting for 16 hours, C57 mice were intraperitoneally injected with APAP (300mg / kg) to establish an AILI model, and then administered intravenously through the tail vein 3 hours later. 24 hours after APAP poisoning, the mice were euthanized, and blood was collected. After standing at room temperature for 2 hours, the blood was centrifuged at 3000rpm for 20 minutes, and the serum was collected. The ALT and AST levels in the serum were measured. As can be seen from the figure, the ALT and AST levels of mice treated with 2.5 mg / kg WS2@TA were lower than those in the clinical drug NAC group, and it has an excellent therapeutic effect on acute liver injury caused by APAP.

[0052] Figure 16 This is a graph showing the survival rate of mice with APAP-induced acute liver injury treated with WS2@TA nanosheets prepared in Example 1. The specific experimental steps were as follows: healthy mice were randomly divided into three groups (n=6): (2) PBS+APAP, (3) 300mg / kg NAC+APAP, and (3) 2.5mg / kg WS2@TA+APAP. After fasting for 16 hours, C57 mice were intraperitoneally injected with a high dose of APAP (600mg / kg) to establish a mouse model, and the drug was administered through the tail vein 3 hours later. The survival of the mice was recorded every 8 hours for 120 hours. As can be seen from the figure, the survival rate of mice treated with 2.5mg / kg WS2@TA was significantly higher than that of the control group treated with APAP. In addition, the survival rate of this treatment group was also better than that of mice treated with the clinical drug NAC.

[0053] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A tannic acid-modified tungsten disulfide nanosheet for treating acute liver injury caused by acetaminophen, characterized by: The tannic acid modified tungsten disulfide nanosheets are based on tungsten disulfide nanosheets as the core, and the surface of the tungsten disulfide nanosheets is modified with negatively charged tannic acid.

2. The tannic acid modified tungsten disulfide nanosheet according to claim 1, characterized in that: The thickness of the tannic acid modified tungsten disulfide nanosheet is 4-8 nm, and the diameter is 150-250 nm.

3. The tannic acid modified tungsten disulfide nanosheet according to claim 1, characterized in that: The surface of the tannic acid-modified tungsten disulfide nanosheet is negatively charged and can target liver damage sites.

4. A method for preparing tannic acid-modified tungsten disulfide nanosheets according to any one of claims 1 to 3, characterized in that: Tungsten disulfide powder frozen with liquid nitrogen is added to an aqueous solution containing tannic acid, and the mixture is ultrasonically crushed and centrifuged to obtain a supernatant. The obtained supernatant is centrifuged, washed, and freeze-dried to obtain tannic acid-modified tungsten disulfide nanosheets.

5. The preparation method according to claim 4, characterized in that: The mass ratio of tannic acid to tungsten disulfide nanosheets is 1 to 9:

1.

6. The preparation method according to claim 4, characterized in that: The ultrasonic treatment is performed alternately by probe ultrasonic treatment and room temperature water bath ultrasonic treatment. The power of the probe ultrasonic treatment is 80-600W and the total time is 2-9h. The power of the room temperature water bath ultrasonic treatment is 10-200W and the total time is 2-9h.

7. A use of the tannic acid modified tungsten disulfide nanosheets according to any one of claims 1 to 3, characterized in that: Used to prepare nanomedicines for the treatment of acute liver injury induced by acetaminophen.

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