GSH-Fe3-XSe3 nano material as well as preparation method and application thereof

By developing GSH-Fe3-XSe3 nanomaterials, the problem of lack of effective treatment for acute renal injury, especially cisplatin-induced renal damage in the prior art was solved, and higher anti-inflammatory and antioxidant activities were achieved, which significantly improved the therapeutic effect, and had good biocompatibility and stability.

CN119970654AActive Publication Date: 2025-05-13SHANXI MEDICAL UNIV
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Patent Information

Application Number
CN202510454890.1
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-04-11
Publication Date
2025-05-13
Estimated Expiration
2045-04-11

AI Technical Summary

Technical Problem

The prior art lacks effective treatments for acute renal injury (AKI), especially renal damage induced by cisplatin, and currently there are few studies on selenium-related nanomedicines in the treatment of AKI.

Method used

A GSH-Fe3-XSe3 nanomaterial was developed. By reacting GSH with Fe(ClO4)2⋅xH2O and Na2SeO3 under specific conditions, GSH-coated Fe3-XSe3 nanomaterial with a particle size of 150 nm. This nanomaterial has good stability and dispersion in aqueous solution and has high biocompatibility.

Benefits of technology

GSH-Fe3-XSe3 nanomaterials significantly improve anti-inflammatory and antioxidant activities through synergistic effects, can effectively inhibit the production of excessive reactive oxygen species (ROS) and inflammatory factors, significantly improve the therapeutic effect on acute renal injury induced by cisplatin, and have low irritation.

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Abstract

The invention provides a GSH-Fe3-XSe3 nano material as well as a preparation method and application thereof, the GSH-Fe3-XSe3 nano material is applicable to the technical field of nano materials, and the GSH-Fe3-XSe3 nano material is prepared from the following raw materials: 0.175 to 0.32 g of glutathione, 0.033 to 0.066 g of Fe (ClO4) 2xH2O, 0.045 to 0.09 g of Na2SeO3 and 35 to 45 mL of dimethyl sulfoxide; compared with glutathione, the GSH-Fe3-XSe3 nano material provided by the invention has higher synergistic anti-inflammatory and antioxidant activity, and can inhibit the generation of excessive ROS (reactive oxygen species) and inflammatory storm, and meanwhile, the therapeutic effect on cisplatin-induced acute kidney injury can be effectively improved by utilizing the synergistic treatment of the glutathione-coated Fe3-XSe3 nano material.
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Description

Technical Field

[0001] The present application relates to the field of nanomaterial technology, and in particular to a GSH-Fe 3-X Se3 nanomaterials, preparation methods and applications thereof. Background Art

[0002] Acute Kidney Injury (AKI) is one of the common complications in clinical practice. Its clinical manifestations are complex and seriously affect the prognosis of patients. According to an analysis of 154 studies, the incidence of AKI in hospitalized patients is 20.0-31.7%, and the mortality rate is 23%. In addition, even after renal function is restored, AKI often develops into fibrosis and chronic kidney disease. In the past few decades, the global burden of death associated with AKI has exceeded that of heart failure, diabetes, or breast cancer. However, apart from supportive care, there is still no effective treatment for confirmed AKI. Therefore, there is an urgent need to explore advanced treatment strategies to improve the clinical outcomes of AKI.

[0003] The two most common causes of AKI are ischemic injury and nephrotoxic drugs. Cisplatin (Cis) is one of the most commonly used chemotherapy drugs in clinical practice. It is used in the treatment of tumors of various solid organs. Its anti-cancer activity is proportional to the dosage. As the dosage increases, the toxicity of cisplatin becomes more obvious. Among them, cisplatin nephrotoxicity is one of the main side effects. Studies have shown that the incidence of cisplatin renal damage is 20%-30%. According to statistics, 70%-80% of all chemotherapy regimens in my country's anti-cancer chemotherapy treatment regimens are based on cisplatin or are combined with cisplatin.

[0004] Current studies have found that AKI can cause an increase in reactive oxygen species (ROS) and inflammatory factors, thereby inducing cell apoptosis and necrosis. In many studies, glutathione (GSH), as a common antioxidant, has a certain application in the treatment of acute kidney injury, but it often requires a large dosage during its treatment process, and the therapeutic effect is general. As one of the most widely studied nanomaterials, selenium-related nanomedicines have the advantages of high biocompatibility, high bioavailability and low toxicity. In addition, the anti-inflammatory and antioxidant activity of selenium-related nanomedicines has been used in a variety of anti-inflammatory and antioxidant disease models. However, there are currently few studies on the treatment of acute kidney injury with selenium-related nanomedicines. Summary of the invention

[0005] In order to solve one of the above technical defects, the present application provides a GSH-Fe 3-X Se3 nanomaterials, preparation methods and applications thereof.

[0006] According to the first aspect of the present application, a GSH-Fe 3-XSe3 nanomaterials include the following raw materials: GSH 0.175-0.32 g, Fe(ClO4)2⋅xH2O 0.033-0.066 g, Na2SeO3 0.045-0.09 g, and dimethyl sulfoxide 35-45 mL.

[0007] Preferably, the GSH-Fe 3-X Se3 nanomaterials are GSH-coated Fe 3-X Se3 nanomaterials.

[0008] Preferably, the GSH-Fe 3-X Se3 nanomaterials include GSH-Fe3Se3 nanomaterials and GSH-Fe2Se3 nanomaterials.

[0009] Preferably, the GSH is reduced glutathione.

[0010] Preferably, the GSH-Fe 3-X The particle size of Se3 nanomaterial is 150nm.

[0011] According to the second aspect of the present application, a GSH-Fe 3-X Preparation method of Se3 nanomaterial, the GSH-Fe 3-X Se3 nanomaterial is any of the GSH-Fe 3-X Se3 nanomaterial, the preparation method comprises the following steps:

[0012] S1. Add GSH into a three-necked flask containing dimethyl sulfoxide, and stir evenly at a speed of 700-900 r / min to obtain a reaction system A;

[0013] S2. Add Fe(ClO4)2⋅xH2O to reaction system A and stir evenly at a speed of 700-900 r / min to obtain reaction system B;

[0014] S3. In an argon atmosphere, the stirred reaction system B is heated to 135-145° C. and stirred at a speed of 700-900 r / min for 10 min. Thereafter, Na2SeO3 is added to the heated reaction system B and stirred continuously for 16-22 h to obtain a reaction system C.

[0015] S4, cooling the reaction system C to 25°C, and then centrifugally washing the cooled reaction system C with isopropanol to obtain GSH-Fe 3-X Se3 nanomaterials;

[0016] S5. The obtained GSH-Fe 3-X The Se3 nanomaterials were collected by freeze-drying and stored at room temperature.

[0017] Preferably, in S4, the volume ratio of isopropanol to the cooled reaction system C is 8:1.

[0018] Preferably, in S4, the centrifugal speed is 15000-18000 r / min, the centrifugal time is 10-30 min, and the centrifugal temperature is 4-25° C.; in S5, the freeze-drying time is 24 h.

[0019] Preferably, in said S5, the obtained GSH-Fe 3-X The mass of Se3 nanomaterial is 40 mg.

[0020] According to the third aspect of the present application, there is provided a GSH-Fe 3-X Application of Se3 nanomaterials in the preparation of drugs for the treatment of acute kidney injury.

[0021] The beneficial effects of the present application are: the GSH-Fe 3-X GSH and Fe in Se3 Nanomaterials 3-X Se3 has a synergistic effect, so the GSH-Fe 3-X Se3 nanomaterials have higher anti-inflammatory and antioxidant activities than GSH, which can inhibit the generation of excessive ROS and inflammatory storms. 3-X Se3 nanomaterials have good stability and dispersibility in aqueous solution, and GSH-Fe 3-X Se3 nanomaterials also have good biocompatibility and low irritation in vivo. 3-X The synergistic therapy of Se3 nanomaterials can effectively improve the therapeutic effect on cisplatin-induced acute kidney injury. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 GSH-Fe provided in Example 1 of the present application 3-X Scanning electron microscope image of Se3 nanomaterials;

[0023] Figure 2 GSH-Fe provided in Example 1 of the present application 3-X Infrared spectrum of Se3 nanomaterials;

[0024] Figure 3 GSH-Fe provided in Example 1 of the present application 3-X XPS graph of Se3 nanomaterials; A is GSH-Fe 3-X The full XPS spectrum of Se3 nanomaterials, B is the detailed XPS spectrum of Se, and C is the detailed XPS spectrum of Fe;

[0025] Figure 4 GSH-Fe provided in Example 1 of the present application 3-X Stability characterization diagram of Se3 nanomaterials;

[0026] Figure 5 GSH-Fe provided in Example 1 of the present application 3-X Fluorescence effect diagram of Se3 nanomaterials eliminating ROS in RAW264.7 cells;

[0027] Figure 6 GSH-Fe provided in Example 1 of the present application 3-X Quantitative characterization of Se3 nanomaterials eliminating ROS in RAW264.7 cells;

[0028] Figure 7 GSH-Fe provided in Example 1 of the present application 3-X Bar graph showing the effect of Se3 nanomaterials on the expression levels of inflammatory factors in RAW264.7 cells;

[0029] Figure 8 The different concentrations of GSH-Fe provided in Example 1 of the present application 3-X Cell activity diagram of RAW264.7 cells after treatment with Se3 nanomaterials;

[0030] Fig. 9 GSH-Fe provided for this application 3-X Experimental diagram of the effect of Se3 nanomaterials on acute kidney injury markers; A is a H&E section of mouse kidney, and B is a Tunel staining image of mouse kidney;

[0031] Fig.10 GSH-Fe provided in Example 1 of the present application 3-X Se3 nanomaterial blood compatibility test diagram; A is GSH-Fe 3-X Se3 nanomaterial blank comparison chart, B is GSH-Fe 3-X Diagram of the hemolytic activity of Se3 nanomaterials. DETAILED DESCRIPTION

[0032] In order to make the technical solutions and advantages in the embodiments of the present application more clearly understood, the exemplary embodiments of the present application are further described in detail below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present application, rather than an exhaustive list of all the embodiments. It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict.

[0033] The reagents and materials in the examples, unless otherwise specified, can be purchased from the market; the test methods in the following examples, unless otherwise specified, are conventional methods in the art.

[0034] RAW264.7 cells (Wuhan Pronosai Life Science Co., Ltd.); C57BL / 6 mice (Beijing Huafukang Biotechnology Co., Ltd.); infrared spectrometer model NICOLET iS 50; XPS instrument model EXCALAB 250 XI; dynamic light scattering instrument model Malvern Zetasizer Nano ZS90; flow cytometer (BD); scanning electron microscope (ApreoC); NO detection kit (Beyotime); inverted fluorescence microscope model ECLIPSE Ts2; fluorescence microplate reader model Synergy NEO; microplate reader model synergy lx; enzyme-linked immunosorbent assay kit (elabscience).

[0035] Example 1

[0036] The present application provides a GSH-Fe 3-X Se3 nanomaterials include the following raw materials: GSH 0.175-0.32 g, Fe(ClO4)2⋅xH2O 0.033-0.066 g, Na2SeO3 0.045-0.09 g, and dimethyl sulfoxide 35-45 mL.

[0037] In specific implementation, the GSH-Fe 3-X Se3 nanomaterials include the following raw materials: GSH 0.32 g, Fe(ClO4)2⋅xH2O 0.066 g, Na2SeO3 0.045 g, and dimethyl sulfoxide 40 mL.

[0038] Furthermore, the GSH-Fe 3-X Se3 nanomaterials are GSH-coated Fe 3-X Se3 nanomaterials.

[0039] Furthermore, the GSH-Fe 3-X Se3 nanomaterials include GSH-Fe3Se3 nanomaterials and GSH-Fe2Se3 nanomaterials. Among them, the valence state of Fe element in GSH-Fe3Se3 nanomaterials is positive divalent and the valence state of Se element is negative divalent; the valence state of Fe element in GSH-Fe2Se3 nanomaterials is positive trivalent and the valence state of Se element is negative divalent.

[0040] Furthermore, the GSH is reduced glutathione, which is used to reduce the positive tetravalent selenium in Na2SeO3 to negative divalent selenium.

[0041] Furthermore, the GSH-Fe 3-X The particle size of Se3 nanomaterial is 150nm.

[0042] The present application also provides a GSH-Fe 3-X The preparation method of Se3 nanomaterials specifically comprises the following steps:

[0043] S1. Add 0.32 g of GSH into a three-necked flask containing 40 mL of dimethyl sulfoxide, and stir evenly at a speed of 900 r / min to obtain a reaction system A;

[0044] S2. Add 0.066 g Fe(ClO4)2⋅xH2O into reaction system A and stir evenly at a speed of 900 r / min to obtain reaction system B;

[0045] S3. In an argon atmosphere, the stirred reaction system B was heated to 140° C. and stirred at a speed of 900 r / min for 10 min. Thereafter, 0.045 g of Na2SeO3 was added to the heated reaction system B and stirred continuously for 18 h to obtain a reaction system C.

[0046] S4, cooling the reaction system C to 25°C, and then centrifugally washing the cooled reaction system C with isopropanol. Centrifugal washing can purify and precipitate the cooled reaction system C, and finally obtain a brown-black precipitate, namely GSH-Fe 3-X Se3 nanomaterials;

[0047] S5, the obtained GSH-Fe 3-X The Se3 nanomaterials were placed in a freeze dryer for 24 h, collected, and stored at room temperature for subsequent use.

[0048] Furthermore, in S4, the volume ratio of isopropanol to reaction system C is 8:1.

[0049] Further, in S4, the centrifugal speed is 15000-18000 r / min, the centrifugal time is 10-30 min, and the centrifugal temperature is 4-25° C. In specific implementation, the centrifugal speed is 15000 r / min, the centrifugal time is 20 min, and the centrifugal temperature is 25° C.

[0050] Further, in said S5, the obtained GSH-Fe 3-X The mass of Se3 nanomaterial is 40 mg.

[0051] In order to better understand the essence of the present application, the GSH-Fe prepared in this example 3-X Se3 nanomaterials were characterized.

[0052] The GSH-Fe prepared in this example was examined by scanning electron microscopy (SEM). 3-X Se3 nanomaterials were characterized. Figure 1As shown, GSH-Fe 3-X The particle size of Se3 nanomaterial is 150nm.

[0053] The present invention uses an infrared spectrometer to analyze the GSH-Fe 3-X Se3 nanomaterials were characterized. Figure 2 As shown, by comparing GSH and GSH-Fe 3-X Infrared spectra of Se3 nanomaterials confirmed the GSH-Fe 3-X Conjugation between Se3 nanomaterials and GSH. 3-X In the infrared spectrum of Se3 nanomaterials, 2524 cm ﹣1 The S─H stretching vibration band at 1716cm disappears due to the formation of Fe─S coordination bond, which means that GSH molecules bind to FeSe through thiol bonds. ﹣1 The absorption band at corresponds to the >C═O stretching mode of the GSH carboxyl group.

[0054] The present invention uses XPS instrument to analyze the GSH-Fe 3-X Se3 nanomaterials were characterized, such as Figure 3 As shown in the figure, it can be concluded that GSH-Fe 3-X The selenium element in Se3 nanomaterials is negative divalent, and the iron element is positive divalent and positive trivalent, indicating that the positive divalent and positive trivalent iron elements exist at the same time, further proving that GSH-Fe 3-X Se3 nanomaterials include GSH-Fe3Se3 nanomaterials and GSH-Fe2Se3 nanomaterials.

[0055] From the above characterization results, it can be seen that the GSH-Fe 3-X Se3 nanomaterials.

[0056] In addition, the present invention also uses a dynamic light scattering instrument to analyze the GSH-Fe 3-X The aqueous solution stability of Se3 nanomaterials was characterized. Figure 4 As shown, GSH-Fe 3-X The particle size and polydispersity coefficient of Se3 nanomaterials remained basically stable within a week. 3-X Se3 nanomaterials can maintain good stability within a week.

[0057] Example 2

[0058] GSH-Fe 3-X Experiment on removing reactive oxygen species in RAW264.7 cells using Se3 nanomaterials.

[0059] To detect GSH-Fe3-X Se3 nanomaterials have the ability to eliminate reactive oxygen species in activated macrophages. An inverted fluorescence microscope and flow cytometer were used to detect the fluorescence intensity of reactive oxygen species in RAW264.7 cells after various treatments.

[0060] In the specific implementation, the inverted fluorescence microscope detection method is as follows: activated RAW264.7 cells are plated at 1×10 6 The cells were seeded at the same density in 6-well plates and incubated for 24 h. Then, lipopolysaccharide (LPS, 1 µg / mL), LPS (1 µg / mL) + GSH (200 µg / mL), and LPS (1 µg / mL) + GSH-Fe 3-X Se3 nanomaterials (200µg / mL) were added, and a blank control group was set up. After the cells were incubated with the drugs for 24 hours, the cells were washed three times with phosphate buffered saline (PBS) and stained with reactive oxygen probe (DCFH-DA) for 30 minutes. The cell samples were washed again with PBS and observed under an inverted fluorescence microscope. The excitation wavelength and emission wavelength of the inverted fluorescence microscope were 488nm and 525nm, respectively. The results are shown in Figure 5 shown.

[0061] The flow cytometer detection method is as follows: activated RAW264.7 cells are plated at 1×10 6 The cells were seeded at 100 μg / mL in a 6-well plate and cultured in a 37°C, 5% CO2 incubator for 24 h. Then, LPS (1 μg / mL), LPS (1 μg / mL) + GSH (200 μg / mL), and LPS (1 μg / mL) + GSH-Fe 3-X Se3 nanomaterials (200µg / mL) were added, and a blank control group was set up. After the cells were incubated with the drugs for 24h, the cells were washed three times with PBS and stained with DCFH-DA for 30min. The cell samples were washed again with PBS, and the cell samples were collected and tested in a flow cytometer. The results are shown in Figure 6 shown.

[0062] from Figure 5 It can be seen that after 24 hours of incubation with LPS-induced RAW264.7 cells, the fluorescence intensity of reactive oxygen species in the model group (LPS) was the strongest, while in the experimental groups with the addition of nanomaterials, the fluorescence intensity of reactive oxygen species in the cells showed a decrease to varying degrees, and it can be found that GSH-Fe 3-X Se3 nanomaterials are more efficient in eliminating reactive oxygen species than GSH alone, which also proves that GSH-Fe 3-X Se3 nanomaterials have stronger ability to eliminate active oxygen. Flow cytometry also showed the same trend, such as Figure 6As shown in the results, the fluorescence intensity of active oxygen in the model group (LPS) was the strongest, while the fluorescence intensity of active oxygen in the cells of each experimental group treated with nanomaterials decreased to varying degrees, and GSH-Fe 3-X Se3 nanomaterials are more efficient in eliminating reactive oxygen species than GSH alone, which also proves that GSH-Fe 3-X Se3 nanomaterials have stronger ability to eliminate active oxygen. 3-X Se3 nanomaterials have good ability to eliminate reactive oxygen species in macrophages.

[0063] Example 3

[0064] GSH-Fe 3-X The effect of Se3 nanomaterials on the expression level of inflammatory factors in RAW264.7 cells. The inflammatory factors include NO, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6).

[0065] In the specific implementation, the NO detection kit was used to measure the NO concentration. More specifically, RAW264.7 cells were cultured at 4×10 4 The cells were inoculated in 96-well plates and cultured overnight for 24 h. Then, LPS (1 µg / mL), LPS (1 µg / mL) + GSH (200 µg / mL), and LPS (1 µg / mL) + GSH-Fe 3-X Se3 nanomaterials (200µg / mL) and a blank control group were set up. After the cells and drugs were incubated for 24h, the supernatant was collected by centrifugation (12000g, 5min, 4℃). The NO concentration was then detected using a NO detection kit, and the OD value was measured at 540nm using an enzyme reader.

[0066] In addition, the concentrations of TNF-α and IL-6 were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Specifically, RAW264.7 cells were plated at 4 × 10 4 The cells were seeded in a 96-well plate and cultured in an incubator for 24 h. Then, LPS (1 µg / mL), LPS (1 µg / mL) + GSH (200 µg / mL), and LPS (1 µg / mL) + GSH-Fe 3-X Se3 nanomaterials (200µg / mL) were added, and a blank control group was set up. After the cells and drugs were incubated for 24 hours, the supernatant was collected. Subsequently, TNF-α and IL-6 were detected using the corresponding inflammatory factor kit, and the OD value was measured at 450nm using an enzyme reader.

[0067] like Figure 7As shown in the figure, after 24h incubation with LPS-induced RAW264.7 cells, the amount of inflammatory factors in the model group (LPS) was the highest, while the intensity of intracellular inflammation in each experimental group treated with drugs decreased to varying degrees, indicating that GSH and GSH-Fe 3-X Se3 nanomaterials can inhibit the release of inflammatory factors by macrophages. 3-X Se3 nanomaterials are significantly more effective in eliminating inflammation than GSH alone, which also proves that GSH-Fe 3-X Se3 nanomaterials have stronger anti-inflammatory ability.

[0068] Example 4

[0069] GSH-Fe 3-X Toxicity assessment of Se3 nanomaterials.

[0070] Specifically, the access density in a 96-well plate was 5 × 10 4 RAW264.7 cells were cultured in an incubator at 37°C and 5% CO2 for 24 h, and then different concentrations of GSH-Fe 3-X Se3 nanomaterials (0, 12.5, 25, 50, 100, 200, 400 μg / mL) were co-cultured, and three replicate wells were set for each concentration; the 96-well plate was placed in an incubator at 37°C and 5% CO2 for 24 h; after the incubation, the supernatant was aspirated, and fresh culture medium containing CCK-8 was added. The plate was placed in the incubator for another 20 min, and the absorbance of all samples at 450 nm was detected using an enzyme marker. The results are shown in Figure 2. Figure 8 As shown in the figure, the viability of RAW264.7 cells is still greater than 80% at a concentration of 200 μg / mL, indicating that the GSH-Fe 3-X Se3 nanomaterials have low toxicity.

[0071] Example 5

[0072] GSH-Fe 3-X Effects of Se3 nanomaterials on acute kidney injury mouse model.

[0073] The specific experimental method is as follows: cisplatin was used to model acute renal injury. After 72 hours of the experiment, the mice were killed by dislocation of the neck and the kidneys were collected. The organ tissues were fixed with 4% paraformaldehyde fixative for subsequent histological pathological section staining. In addition, tunnel staining was performed on the kidneys of mice in different treatment groups to observe the apoptosis of renal lymphocytes.

[0074] like Fig. 9 As shown, compared with the Control group, the renal epithelial cells in the cisplatin-induced model group (Cis group) dropped out after injection of GSH-Fe 3-XAfter Se3 nanomaterials, compared with GSH treatment, GSH-Fe 3-X In mice treated with Se3 nanomaterials, renal epithelial cell shedding was reduced and lymphocyte apoptosis was more inhibited. It can be seen that with the increase of the dosage concentration (200, 400, 800 mg / kg), the therapeutic effect was not much different. This proves that GSH-Fe 3-X The appropriate dosing concentration of Se3 nanomaterials in mice is 200 mg / kg. It has excellent synergistic anti-inflammatory and antioxidant activity, can clear ROS in mice with acute kidney injury and reduce the expression level of inflammatory factors, effectively alleviating the organ damage caused by acute kidney injury.

[0075] Example 6

[0076] GSH-Fe 3-X Blood compatibility of Se3 nanomaterials.

[0077] The specific experimental method is as follows: First, remove the eyeballs of healthy mice to collect fresh blood, collect the obtained fresh blood in anticoagulant tubes, shake evenly and centrifuge (1500r / min, 20 min) to collect red blood cells. Secondly, use PBS to resuspend the red blood cells (the volume ratio of PBS to red blood cells is 49:1), centrifuge and wash (3000r / min, 10min) until the supernatant has no obvious red color. Then, take 20μL of red blood cells and add 980μL of GSH-Fe containing different concentrations. 3-X Finally, ultrapure water and PBS were used as positive and negative controls, respectively, and GSH-Fe 3-X The PBS solution of Se3 nanomaterials (200, 100, 50, 25, 12.50 µg / mL) was used as a blank control and placed at room temperature for 2 hours. After the incubation, the solution was centrifuged at 15,000 r / min for 3 minutes, photographed, and 100 µL of the supernatant was placed in a 96-well plate. The OD value was detected at 540 nm using an ELISA reader. The hemolysis rate was calculated according to the following formula:

[0078]

[0079] like Fig.10 As shown, the red blood cells dissolved in ultrapure water were used as the positive control group, the red blood cells dissolved in PBS were used as the negative control group, and the red blood cells dissolved in PBS were used as the negative control group. 3-X The PBS solution of Se3 nanomaterials was used as the blank control group, and the corresponding concentrations of GSH-Fe 3-XThe red blood cells dissolved by PBS solution of Se3 nanomaterials are the experimental group. As can be seen from the figure, the blood cells in the positive control group are completely lysed, while the blood cells in the negative control group are not lysed. The hemolysis rate is calculated by subtracting the absorbance value of the blank control group from the different concentration material groups (12.5, 25, 50, 100, 200 µg / mL) to obtain the GSH-Fe 3-X When the concentration of Se3 nanomaterials was 200 μg / mL, the hemolysis rate of blood cells did not exceed 5%, indicating that GSH-Fe 3-X Se3 nanomaterials have good blood compatibility.

[0080] GSH-Fe in Examples 2 to 6 3-X The Se3 nanomaterials are all GSH-Fe prepared in Example 1 3- X Se3 nanomaterials; the incubator in Examples 2 to 4 may be a constant temperature incubator.

[0081] The present application provides a GSH-Fe 3-X GSH and Fe in Se3 Nanomaterials 3-X Se3 has a synergistic effect, so the GSH-Fe 3-X Se3 nanomaterials have higher anti-inflammatory and antioxidant activities than GSH, and can inhibit the generation of excessive ROS and inflammatory storms. 3-X The synergistic treatment of Se3 nanomaterials can effectively improve the therapeutic effect of cisplatin-induced acute kidney injury. 3-X Se3 nanomaterials have good stability and dispersibility in aqueous solution, and GSH-Fe 3-X Se3 nanomaterials also have good biocompatibility and low irritation in vivo. 3-X The product system of Se3 nanomaterials is simple, the product can be directly stored and used, and the preparation method is simple.

[0082] Although the preferred embodiments of the present application have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications falling within the scope of the present application.

[0083] Obviously, those skilled in the art can make various changes and modifications to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application fall within the scope of the claims of the present application and their equivalents, the present application is also intended to include these modifications and variations.

Claims

1. A GSH-Fe 3-X Se3 nanomaterial, characterized by: The method comprises the following raw materials: glutathione 0.175-0.32 g, Fe(ClO4)2·xH2O 0.033-0.066 g, Na2SeO3 0.045-0.09 g, and dimethyl sulfoxide 35-45 mL.

2. GSH-Fe according to claim 1 3-X Se3 nanomaterial, characterized by: The GSH-Fe 3-X Se3 nanomaterials are glutathione-coated Fe 3-X Se3 nanomaterials.

3. GSH-Fe according to claim 1 3-X Se3 nanomaterial, characterized by: The GSH-Fe 3-X Se3 nanomaterials include GSH-Fe3Se3 nanomaterials and GSH-Fe2Se3 nanomaterials.

4. GSH-Fe according to claim 1 3-X Se3 nanomaterial, characterized by: The glutathione is reduced glutathione.

5. GSH-Fe according to claim 1 3-X Se3 nanomaterial, characterized by: The GSH-Fe 3-X The particle size of Se3 nanomaterial is 150nm.

6. GSH-Fe according to any one of claims 1-5 3-X The preparation method of Se3 nanomaterial is characterized by: The following steps are involved: S1. Add glutathione into a three-necked flask containing dimethyl sulfoxide, and stir evenly at a speed of 700-900 r / min to obtain a reaction system A; S2. Add Fe(ClO4)2⋅xH2O to reaction system A and stir evenly at a speed of 700-900 r / min to obtain reaction system B; S3. In an argon atmosphere, the stirred reaction system B is heated to 135-145° C. and stirred at a speed of 700-900 r / min for 10 min. Thereafter, Na2SeO3 is added to the heated reaction system B and stirred continuously for 16-22 h to obtain a reaction system C. S4, cooling the reaction system C to 25°C, and then centrifugally washing the cooled reaction system C with isopropanol to obtain GSH-Fe 3-X Se3 nanomaterials; S5. The obtained GSH-Fe 3-X The Se3 nanomaterials were collected by freeze-drying and stored at room temperature.

7. GSH-Fe according to claim 6 3-X The preparation method of Se3 nanomaterial is characterized by: In S4, the volume ratio of isopropanol to the cooled reaction system C is 8:

1.

8. GSH-Fe according to claim 6 3-X The preparation method of Se3 nanomaterial is characterized by: In S4, the centrifugal speed is 15000-18000 r / min, the centrifugal time is 10-30 min, and the centrifugal temperature is 4-25° C.; In S5, the freeze-drying time is 24 hours.

9. GSH-Fe according to claim 6 3-X The method for preparing Se3 nanomaterials is characterized by: In S5, the obtained GSH-Fe 3-X The mass of Se3 nanomaterial is 40 mg.

10. GSH-Fe according to any one of claims 1-5 3-X Application of Se3 nanomaterials in the preparation of drugs for the treatment of acute kidney injury.

Citation Information

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