M2M-SeMSN-coated C176 nanoparticles, and preparation method and application thereof

Abstract

The invention discloses an M2M-SeMSN-coated C176 nano-particle, a preparation method and application thereof, the nano-particle comprises an STING inhibitor C176 and a carrier, and the carrier is based on an M2 macrophage membrane and a selenium-bridged mesoporous silica nano-particle. Specifically, the M2M-SeMSN-coated C176 nano-particles are obtained by loading an STING inhibitor C176 by using a selenium-bridged mesoporous silica nano-particle SeMSN and M2 macrophage cell membrane. The invention further discloses a preparation method of the M2M-SeMSN-coated C176 nano-particles. The M2M-SeMSN-coated C176 nanoparticles can be used for preparing a medicine for treating acute kidney injury.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine, and provides M2M-SeMSN@C176 nanoparticles, a preparation method and applications thereof. BACKGROUND

[0002] Acute kidney injury (AKI) is a common clinical critical illness, with about 13.3 million patients diagnosed and about 1.7 million deaths worldwide each year. It is worth noting that a considerable proportion of AKI patients who survive will further develop chronic kidney disease, and even progress to end-stage renal disease. As one of the organs with the highest energy demand in the human body, the kidney has the second highest mitochondrial content after the heart, especially in renal tubular epithelial cells. AKI induced by various factors can cause mitochondrial damage, and further trigger energy metabolism disorder and elevated levels of reactive oxygen species (ROS) in the kidney. Damaged or dead renal tubular epithelial cells release mitochondrial DNA (mtDNA), activating the cGAS-STING signaling pathway. The activation of the pathway promotes the phosphorylation of downstream transcription factors such as interferon regulatory factor 3 (IRF3), and ultimately drives the explosive expression of type I interferon and various pro-inflammatory cytokines, recruits and activates immune cells such as macrophages, forms a vicious inflammatory cycle, and exacerbates kidney tissue damage. Therefore, the cGAS-STING pathway plays a core role in the inflammatory cascade of AKI, and becomes a highly potential therapeutic intervention target.

[0003] Small molecule inhibitors show broad clinical translation prospects by precisely blocking the core inflammatory loop in AKI. Although there are precedents for intervention strategies targeting the cGAS-STING axis, such as H151 (PMID: 33615891, 37102684), Compound 4dc (PMID: 40327997), Compound 66 (PMID: 40188441), and C23 (PMID: 29434211), the aforementioned lead molecules still face common bottlenecks such as poor target selectivity, insufficient oral exposure, and narrow safety window, necessitating the iteration and upgrading of a new generation of highly selective and highly drug-like inhibitors. C176 is a highly efficient cGAS-STING pathway small molecule inhibitor discovered in 2018, which can covalently target and palmitoylate cysteine residue 91 (Cys91) on the STING protein, block its oligomerization, and thus inhibit the activation of downstream inflammatory factors, showing good therapeutic prospects. However, such inhibitors face significant challenges in clinical translation, such as poor water solubility, rapid in vivo metabolism, low bioavailability, and lack of kidney targeting, which limits their therapeutic efficacy and may cause systemic side effects, limiting their clinical application. Therefore, it is urgent to develop new drug delivery systems to overcome the above bottlenecks. SUMMARY

[0004] Therefore, the purpose of the present application is to provide M2M-SeMSN@C176 nanoparticles, a preparation method and applications thereof, aiming to solve the clinical application problem of small molecule inhibitor C176.

[0005] To achieve the above-mentioned purpose, the present application provides the following technical solutions. The present application provides M2M-SeMSN@C176 nanoparticles, which are obtained by loading STING inhibitor C176 on mesoporous silica nanoparticles SeMSN bridged by diselenium, M2 macrophage membrane; wherein the mass ratio of C176, SeMSN, and M2 macrophage membrane is 1:20:105, the Chinese name of C176 is N-(4-iodophenyl)-5-nitrofuran-2-formamide, and the molecular formula is C 11 H7IN2O4, and the chemical structure is as follows: .

[0006] As one of the preferred technical solutions, the mesoporous silica nanoparticles SeMSN bridged by diselenium is prepared by the following method: first, mix cetyltrimethylammonium p-toluenesulfonate, triethanolamine, and deionized water and stir, then slowly add tetraethyl orthosilicate and bis[3-(triethoxysilyl)propyl]diselenide, continue to stir, centrifuge to obtain the precipitate, wash with anhydrous ethanol, add an ethanol solution of ammonium nitrate, heat and reflux, centrifuge to obtain the precipitate, and dry.

[0007] As one of the further preferred technical solutions, the use amount ratio of hexadecyl trimethyl ammonium p-toluene sulfonate, triethanolamine, deionized water, tetraethyl orthosilicate, bis[3-(triethoxysilyl)propyl] diselenide, and the ethanol solution of ammonium nitrate is 0.1-10 g: 0.01-10 g: 0.01-100 mL: 0.01-10 g: 0.01-10 g: 0.01-100 mL, wherein the mass concentration of the ethanol solution of ammonium nitrate is 0.01-10%.

[0008] As one of the further preferred technical solutions, the use amount ratio of hexadecyl trimethyl ammonium p-toluene sulfonate, triethanolamine, deionized water, tetraethyl orthosilicate, bis[3-(triethoxysilyl)propyl] diselenide, and the ethanol solution of ammonium nitrate is 0.1-10 g: 0.01-10 g: 0.01-100 mL: 0.01-10 g: 0.01-10 g: 0.01-100 mL, wherein the mass concentration of the ethanol solution of ammonium nitrate is 0.01-10%.

[0009] As one of the further preferred technical solutions, the mixing and stirring condition is 80℃ mixing and stirring for 30 minutes; the continuous stirring condition is stirring for 4 hours at 80℃ and 1000 rpm; and the heating reflux time is 12 hours.

[0010] The application also provides a preparation method of the M2M-SeMSN@C176 nanoparticle, and the specific steps are as follows: S1. First, the diselenide bridged mesoporous silica nanoparticle SeMSN is dissolved in deionized water and uniformly ultrasonically dispersed to obtain a SeMSN aqueous solution; and the C176 is dissolved in dimethyl sulfoxide (DMSO) to obtain a C176 solution; S2. Then, the SeMSN aqueous solution and the C176 solution are mixed and vortexed, and the precipitate is obtained by centrifugation to obtain the C176-loaded nanoparticle, namely SeMSN@C176; S3. Then, the SeMSN@C176 is dispersed in deionized water and ultrasonically treated to obtain a nanoparticle dispersion liquid; and the M2 macrophage membrane is diluted with deionized water to obtain a cell membrane solution; S4. Finally, the nanoparticle dispersion liquid and the cell membrane solution are mixed, vortexed, ultrasonically treated in an ice water bath, and centrifuged to obtain the precipitate.

[0011] As one of the preferred technical solutions, in step S1, the ultrasonic dispersion time is 10 minutes, the concentration of the SeMSN aqueous solution is 1 mg / mL, and the concentration of the C176 solution is 0.5 mg / mL.

[0012] As one of the preferred technical solutions, in step S2, the volume ratio of the SeMSN aqueous solution to the C176 solution is 10:1, and the mixing and vortexing time is 5 minutes.

[0013] As one of the preferred technical solutions, in step S3, the concentration of the nanoparticle dispersion liquid is 1 mg / mL, and the concentration of the cell membrane solution is 5 mg / mL.

[0014] As one of the preferred technical solutions, in step S4, the volume ratio of the nanoparticle dispersion liquid to the cell membrane solution is 1:1, the vortex time is 1 minute, the ultrasonic treatment time in the ice water bath is 10 minutes, and the centrifugation condition is 3℃, 3000 rpm, and centrifugation for 1 minute.

[0015] The application further provides application of the M2M-SeMSN@C176 nanoparticle in preparation of an acute kidney injury treatment drug.

[0016] The application has the following beneficial effects: The application provides an M2M-SeMSN@C176 nanoparticle, a preparation method and application thereof. The nanoparticle comprises two parts of a STING inhibitor C176 and a carrier. The carrier is based on a M2 macrophage membrane and diselenide-bridged mesoporous silica nanoparticles (SeMSN). Specifically, the M2M-SeMSN@C176 nanoparticle is obtained by loading the STING inhibitor C176 on the diselenide-bridged mesoporous silica nanoparticles SeMSN and the M2 macrophage membrane. The M2M-SeMSN@C176 nanoparticle can be used in preparation of an acute kidney injury treatment drug.

[0017] Nanoparticles are widely used in the development of new drug delivery systems due to their adjustable size, controllable structure and surface properties, good targeting and low toxicity. Among them, mesoporous silica nanomaterials have high specific surface area, adjustable pore structure and good biocompatibility, providing an ideal platform for drug loading and controlled release. To achieve efficient targeting and intelligent release of nanomaterials in the lesion area of the kidney, the invention has multiple functional design: on the one hand, taking advantage of the pathological feature that ROS level is significantly increased due to mitochondrial damage in AKI, a ROS-sensitive Se-Se bond is introduced into the nanoskeleton as a responsive drug release switch to achieve precise drug release at the damage site; on the other hand, based on the high expression of intercellular adhesion molecule-1 (ICAM-1) in renal tubular cells after AKI damage, and the natural high expression of CD18, the ligand of M2 macrophage membrane surface, can mediate active targeting recognition; at the same time, M2 macrophage membrane also highly expresses CD47 protein, which effectively avoids being phagocytosed by immune cells by transmitting the "don't eat me" signal, and is rich in various inflammation-related cytokine receptors, which helps to neutralize local inflammatory mediators. Therefore, coating the nanomaterial with M2 macrophage membrane can synergistically endow it with efficient damaged renal tubular targeting ability, excellent immune escape function and inflammation regulation potential.

[0018] The M2M-SeMSN@C176 nanoparticles prepared by the invention have the advantages of high loading capacity, active targeting, efficient release, immune escape, etc. In vitro and in vivo experiments show that they have high efficient targeting ability to damaged kidneys and renal tubular epithelial cells, can effectively inhibit the abnormal activation of the cGAS-STING pathway and the release of related inflammatory factors, significantly improve the survival rate of renal tubular epithelial cells under hypoxia / reoxygenation conditions, and in animal models, it is confirmed that it can significantly reduce acute kidney injury caused by ischemia-reperfusion by inhibiting excessive inflammatory response. The nanometer preparation provides a new strategy and candidate scheme for the treatment of clinical AKI, and has important clinical application potential and transformation value.

[0019] Specifically, the invention has the following advantages: 1. Immune escape and long circulation: The M2 macrophage membrane surface highly expresses CD47 protein, which can transmit the "don't eat me" signal by combining with the SIRP alpha receptor on the surface of macrophages, effectively block the recognition and removal of the reticuloendothelial system, significantly reduce the uptake of the monocyte-macrophage system, and prolong the circulation half-life of the nanoparticles in the blood.

[0020] 2. Lesion active targeting: M2 macrophages have high expression of CD18 (integrin β2) and other functional adhesion molecules on the cell membrane surface, which can specifically recognize and bind to the high expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of renal tubular cells after AKI injury. The receptor-ligand interaction can mediate the active homing and enrichment of nanoparticles to the diseased kidney, thereby significantly improving the targeting efficiency at the lesion site.

[0021] 3. Lesion microenvironment-responsive drug release: The diselenide bond (Se-Se) in the nanoparticle skeleton is highly sensitive to the high level of ROS produced after AKI injury, which can rapidly break, achieving precise and rapid drug release at the lesion site, improving local drug concentration and reducing systemic exposure risk.

[0022] 4. High drug loading and biocompatibility: Mesoporous silica nanoparticles have a large specific surface area and regular pore structure, providing high loading capacity for C176; at the same time, the silica material itself has good biocompatibility, and the M2 macrophage membrane coating further enhances its biological safety.

[0023] Other advantages, objects, and features of the present application will be in part apparent and in part pointed out hereinafter. The objects and other advantages of the present application can be achieved and obtained by means of the following description. BRIEF DESCRIPTION OF DRAWINGS

[0024] In order to make the purposes, technical solutions and advantages of the present application more clear, the preferred detailed description of the present application will be combined with the drawings as follows, wherein: Figure 1 . Basic characterization of diselenide bridged mesoporous silica nanoparticles (SeMSN). (A) TEM image of SeMSN; (B) Nitrogen adsorption-desorption isotherm; (C) Pore size distribution; (D) EDS element mapping (blue: Si, red: Se, yellow: O).

[0025] Figure 2 . Basic characteristics of M2M-SeMSN@C176 nanoparticles. (A) Western Blot analysis of macrophage membrane protein expression; (B-D) ELISA detection of the neutralization ability of the cell membrane to IL-6, TNF-α and IL-1β; (E) TEM image of M2M-SeMSN@C176; (F) Particle size distribution; (G) Zeta potential; (H) Drug release curve under different ROS conditions.

[0026] Figure 3. In vitro and in vivo targeting ability of M2M-SeMSN nanoparticles. (A) Confocal microscopy observation of macrophage phagocytosis of Cy5.5-labeled nanoparticles; (B, C) Flow cytometry quantitative analysis of nanoparticle uptake by macrophages and TCMK1 cells; (D) In vivo fluorescence imaging and quantitative analysis of mouse kidneys after tail vein injection of Cy5.5-labeled M2M-SeMSN nanoparticles.

[0027] Figure 4 . In vitro protective effect of M2M-SeMSN@C176 nanoparticles. (A) Effect of different concentrations of nanoparticles on cell viability; (B) Comparison of cell viability after different treatments; (C) Calcein-AM / PI staining showing live cells (green) and dead cells (red); (D) Expression levels of cGAS-STING pathway-related proteins; (E-G) ELISA detection of inflammatory factor levels in supernatant.

[0028] Figure 5 . In vivo protective effect of M2M-SeMSN@C176 nanoparticles. (A) Kidney gross observation of different treatment groups; (B, C) Serum urea nitrogen and creatinine levels; (D) Kidney tissue HE staining and injury score (Injury score standard: no injury, 0 points; injury area ≤10%, 1 point; 11%-25%, 2 points; 26%-45%, 3 points; 46%-75%, 4 points; ≥76%, 5 points). DETAILED DESCRIPTION

[0029] The application will be further described below in conjunction with the specific embodiments.

[0030] Example 1 Synthesis of M2M-SeMSN@C176 nanoparticles 0.6 g of hexadecyltrimethylammonium p-toluenesulfonate, 0.15 g of triethanolamine, and 40 mL of deionized water were stirred at 80°C for 30 min. Then, 4.0 g of tetraethyl orthosilicate and 1.0 g of bis[3-(triethoxysilyl)propyl] diselenide were slowly added dropwise to the solution. The resulting mixture was stirred at 80°C and 1000 rpm for 4 hours. The product was collected by centrifugation, washed with ethanol three times, and then refluxed in a 1% (w / v) NH4NO3 solution in ethanol for 12 hours. Finally, the synthesized diselenide-bridged mesoporous silica nanoparticles (SeMSN) were collected by centrifugation and dried for use, and the basic characterization results are shown in Table 1. Figure 1 .

[0031] For loading STING inhibitor C176, the synthesized diselenide bridged mesoporous silica nanoparticles were dissolved in deionized water with a concentration of 1 mg / mL and ultrasonicated for 10 min to make them uniformly dispersed. A C-176 solution with a concentration of 0.5 mg / mL was prepared using DMSO. Finally, the nanoparticle solution and the C176 solution were mixed by vortexing for 5 min, and centrifuged to obtain the C-176-loaded diselenide bridged mesoporous silica nanoparticles (SeMSN@C176).

[0032] For loading STING inhibitor C176, the synthesized diselenide bridged mesoporous silica nanoparticles were dissolved in deionized water with a concentration of 1 mg / mL and ultrasonicated for 10 min to make them uniformly dispersed. A C-176 solution with a concentration of 0.5 mg / mL was prepared using DMSO. Finally, the nanoparticle solution and the C176 solution were mixed by vortexing for 5 min, and centrifuged to obtain the C-176-loaded diselenide bridged mesoporous silica nanoparticles (SeMSN@C176).

[0033] RAW264.7 macrophages (CL-0190, Wuhan Pons Genetech Co., Ltd.) were induced with 200 ng / mL LPS (lipopolysaccharide) and 20 ng / mL mouse IL-4 for 24 hours, respectively, to collect M0, M1 and M2 type macrophages. The M2 macrophage membrane was extracted using a cell membrane extraction kit (P0033, Shanghai Biyun Tian Biotechnology Co., Ltd.), and the membrane protein concentration was determined by the BCA method. Western Blot was used to detect the membrane protein level of macrophages, and Elisa kit was used to detect the neutralization ability of macrophage membrane to inflammatory factors, which suggested that the M2 macrophage membrane had higher targeting, neutralization of inflammatory factors and immune escape ability. Figure 2 M2M-SeMSN@C176.

[0034] The C176-loaded nanoparticles (SeMSN@C176) were dispersed in deionized water (1 mg / mL) and ultrasonicated for 10 min. The M2 macrophage membrane was diluted to a protein concentration of 5 mg / mL. The nanoparticle dispersion and the cell membrane solution were mixed at a volume ratio of 1:1, vortexed for 1 min first, then ultrasonicated in an ice water bath for 10 min, and then centrifuged at 4°C and 3000 rpm for 1 min. The precipitate was collected, i.e. M2M-SeMSN@C176 nanoparticles (which can be redispersed to the desired concentration). The basic characterization is shown in Table 1. Figure 2 The particle size was 70.0 ± 9.24 nm, the zeta potential was 12.03 ± 0.83 mV, and it showed significant responsive release characteristics under high ROS conditions.

[0035] Example 2 M2M-SeMSN nanoparticles exhibit better targeting ability in vitro and in vivo To trace the nanomaterials, C176 in the above synthesis steps was replaced by Cy5.5 fluorescent dye to synthesize SeMSN@Cy5.5 and M2M-SeMSN@Cy5.5. The two kinds of nanomaterials were added into RAW264.7 macrophages respectively, and 12 hours later, the phagocytosis of the nanomaterials by macrophages was detected by laser confocal microscopy and flow cytometry. The results are shown in Figure 3 As shown in Figs. 2A and 2B, M2M-SeMSN@Cy5.5 can effectively avoid phagocytosis by macrophages and achieve immune escape. After the two kinds of nanoparticles were co-cultured with TCMK1 cells (STCC20015P, Wuhan Saiver Biotechnology Co., Ltd.) that had undergone hypoxia (37°C, oxygen volume concentration 1%, carbon dioxide volume concentration 5% for 24 hours) / reoxygenation (37°C, carbon dioxide volume concentration 5% for 6 hours) treatment for 12 hours, flow cytometry detection showed that M2M-SeMSN@Cy5.5 had stronger targeting ability to damaged renal epithelial cells (Fig. 2C). Figure 3 Fig. 2D shows the results of Western Blot analysis.

[0036] Six to eight-week-old C57 mice were selected to construct a unilateral kidney ischemia-reperfusion model (the contralateral kidney was reserved). After 1 day of injury, 200 μL of M2M-SeMSN@Cy5.5 (0.1 mg / mL) was injected through the tail vein to evaluate the distribution of the nanoparticles in the healthy and injured kidneys using a small animal live optical imaging system. The results showed that M2M-SeMSN@Cy5.5 had significantly higher enrichment in the acute injury side kidney (Fig. 3A). Figure 3 Fig. 3B shows the results of Western Blot analysis.

[0037] Example 3 Protective effect of M2M-SeMSN@C176 nanoparticles in an in vitro model M2M-SeMSN@C176 nanoparticles containing different concentrations of C176 were co-cultured with normal TCMK1 cells, and cell viability was detected by CCK-8 method. The results are shown in Fig. 4A. Figure 4 As shown in Fig. 4A, the nanoparticles had no obvious toxicity to normal renal epithelial cells. Subsequently, an ischemia / reperfusion model was used to simulate acute kidney injury in vitro, and the equivalent C176 concentration was added in each group. Cell viability was evaluated by CCK-8 method and Calcein-AM / PI staining. The results showed that M2M-SeMSN@C176 exhibited more significant therapeutic effect than free C176 and nanoparticles without cell membrane coating (Figs. 4B and 4C). Figure 4 Western Blot analysis showed that hypoxia / reoxygenation could activate the cGAS-STING pathway, and M2M-SeMSN@C176 could effectively inhibit the activation of the pathway (Fig. 4D). Figure 4M2M-SeMSN@C176 could effectively inhibit the secretion of inflammatory factors, thus reducing the inflammatory response associated with AKI.

[0038] Example 4 M2M-SeMSN@C176 nanoparticles could effectively reduce the injury of renal ischemia-reperfusion The 6-8 weeks old C57 mice (Beijing Huafukang Bioscience Co., Ltd.) were anesthetized with anesthetic, the back hair was removed, and the skin was disinfected with iodophor. The mice were placed on a heated surgical pad, and the upper and lower limbs of the mice were fixed with low-adhesion tape. The left flank of the mouse was first incised with scissors to enter the retroperitoneal cavity, the left kidney and perirenal fat were separated, and the left kidney was gently pulled out of the incision. The right kidney of the mouse was separated in the same way, and after both kidneys were exposed, the renal artery and vein were clamped with a vascular clamp. The mouse kidney gradually turned black uniformly, and after the clamp was released after 30 minutes, the kidney quickly turned deep pink, indicating that the modeling was successful. The whole process paid attention to the mouse warming.

[0039] Two hours before modeling, the experimental group was injected with free C176, SeMSN@C176 or M2M-SeMSN@C176 equivalent to 750 nM C176 through the tail vein. After 24 hours of modeling, the serum was collected to detect the levels of creatinine and urea nitrogen; the renal tissue was taken for HE staining to evaluate the degree of tissue damage.

[0040] The results are shown in Figure 5 As shown in FIG. 2A, after renal ischemia-reperfusion, the kidney volume was slightly enlarged due to tissue damage, and M2M-SeMSN@C176 treatment could effectively reduce the degree of enlargement. The subsequent detection of serum creatinine and urea nitrogen in mice more directly proved this point. After ischemia-reperfusion treatment, the serum creatinine and urea nitrogen levels of the mice were significantly higher than those of the sham operation group. M2M-SeMSN@C176 could significantly reduce the high levels of creatinine and urea nitrogen caused by ischemia-reperfusion, and the effect was much better than that of free C176 and nanoparticles without cell membrane coating (SeMSN@C176) (FIG. 2A). Figure 5 FIGS. 2B and 2C show that HE staining showed that ischemia-reperfusion caused severe damage to the renal tissue (loss of brush border, tubular dilation, cast formation, necrosis, etc.), and the renal injury score increased; after treatment with M2M-SeMSN@C176, the renal tissue damage was significantly reduced, and the injury score decreased significantly (FIGS. 2B and 2C). Figure 5 FIG. 2D.

[0041] Finally, it should be pointed out that the above examples are only used to illustrate the technical solutions of the present application and are not limiting. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the present application, and they should be covered in the scope of the claims of the present application.

Claims

1. M2M-SeMSN@C176 nanoparticles characterized in that, The STING inhibitor C176 was obtained by loading mesoporous silica nanoparticles SeMSN and M2 macrophage membranes using diselenide bridging; the mass ratio of C176, SeMSN, and M2 macrophage membrane was 1:20:

105.

2. The M2M-SeMSN@C176 nanoparticle of claim 1, wherein, Selenium-bridged mesoporous silica nanoparticles (SeMSN) were prepared by the following method: First, hexadecyltrimethyl-p-toluenesulfonate ammonium, triethanolamine, and deionized water were mixed and stirred. Then, tetraethyl orthosilicate and bis[3-(triethoxysilyl)propyl]diselenoether were slowly added dropwise, and stirring was continued. The precipitate was collected by centrifugation, washed with anhydrous ethanol, added to an ethanol solution of ammonium nitrate, heated under reflux, centrifuged again, and dried to obtain the final product.

3. The M2M-SeMSN@C176 nanoparticle of claim 2, wherein, The ratio of the volume of the ethanol solution of hexadecyltrimethyl-p-toluenesulfonate, triethanolamine, deionized water, tetraethyl orthosilicate, bis[3-(triethoxysilyl)propyl]diselenoether, and ammonium nitrate is 0.1–10 g : 0.01–10 g : 0.01–100 mL : 0.01–10 g : 0.01–100 mL, wherein the mass concentration of the ethanol solution of ammonium nitrate is 0.01–10%.

4. The M2M-SeMSN@C176 nanoparticle of claim 2, wherein, The mixing conditions were: mixing at 80°C for 30 minutes; the continued mixing conditions were: mixing at 80°C and 1000 rpm for 4 hours; and the reflux heating time was 12 hours.

5. The method for preparing M2M-SeMSN@C176 nanoparticles according to claim 1, characterized in that, The specific steps are as follows: S1. First, dissolve diselelenene-bridged mesoporous silica nanoparticles (SeMSN) in deionized water and disperse them uniformly by ultrasonication to obtain an aqueous solution of SeMSN; dissolve C176 in dimethyl sulfoxide (DMSO) to obtain a C176 solution; S2. Then, the SeMSN aqueous solution and the C176 solution were mixed and vortexed, and the precipitate was collected by centrifugation to obtain C176-loaded nanoparticles, namely SeMSN@C176; S3. SeMSN@C176 was then dispersed in deionized water and sonicated to obtain a nanoparticle dispersion; the M2 macrophage cell membrane was diluted with deionized water to obtain a cell membrane solution. S4. Finally, mix the nanoparticle dispersion with the cell membrane solution, vortex, sonicate in an ice-water bath, centrifuge to collect the precipitate, and obtain the final product.

6. The production method according to claim 5, characterized by, In step S1, the ultrasonic dispersion time is 10 minutes, the concentration of the SeMSN aqueous solution is 1 mg / mL, and the concentration of the C176 solution is 0.5 mg / mL.

7. The preparation method according to claim 5, characterized in that, In step S2, the volume ratio of SeMSN aqueous solution to C176 solution is 10:1, and the mixing vortex time is 5 minutes.

8. The preparation method according to claim 5, characterized in that, In step S3, the concentration of the nanoparticle dispersion is 1 mg / mL, and the concentration of the cell membrane solution is 5 mg / mL.

9. The preparation method according to claim 5, characterized in that, In step S4, the volume ratio of the nanoparticle dispersion to the cell membrane solution is 1:1, the vortexing time is 1 minute, the ultrasonic treatment time in the ice-water bath is 10 minutes, and the centrifugation conditions are: 3℃, 3000rpm, centrifugation for 1 minute.

10. The use of the M2M-SeMSN@C176 nanoparticles according to claim 1 in the preparation of drugs for the treatment of acute kidney injury.

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