Organic meso-porous silicon nanoparticles for blood glucose stabilization and beta cell recovery as well as preparation method and application of organic meso-porous silicon nanoparticles

Abstract

The invention discloses organic meso-porous silicon nanoparticles for blood glucose stabilization and beta cell recovery as well as a preparation method and application thereof. The organic meso-porous silicon nanoparticles comprise an inner core and a coating layer coating the surface of the inner core, the coating layer is composed of a transferrin coating and a deoxycholic acid modification layer; the inner core is composed of insulin, glucose oxidase and an aminated organic mesoporous silicon nano-carrier; the transferrin coating is used for preventing drug leakage and gastrointestinal enzyme degradation, and the deoxycholic acid modification layer is used for enhancing intestinal permeability and realizing liver targeting delivery. According to the invention, the intestinal permeability and liver targeting of the insulin delivery system are improved; under hyperglycemia, H2O2 generated by glucose oxidase can trigger diselenide bond breakage and release insulin as required, the selenium derivative of the nanoparticle gradually increases the level of selenium-containing antioxidant enzyme, inhibits oxidative stress and NF-kappa B mediated inflammation, significantly reduces beta cell apoptosis, significantly recovers the insulin secretion function of beta cells, and has a good application prospect. And pathological driving factors of type 2 diabetes mellitus are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and more particularly to organic mesoporous silicon nanoparticles for stabilizing blood sugar and restoring beta cells, as well as a preparation method and application thereof. Background Art

[0002] Diabetes has become a global health crisis, with 90% of type 2 diabetes mellitus (T2DM) caused by a complex interplay of insulin resistance and progressive β-cell dysfunction, ultimately leading to systemic hyperglycemia and life-threatening complications. While GLP-1 agonists or SGLT2 inhibitors can alleviate hyperglycemia, they fail to address the dual pathology of glucose dysregulation and β-cell dysfunction. Even insulin preparations, the cornerstone of advanced disease management, can exacerbate systemic hyperinsulinemia and hypoglycemia, accelerating β-cell depletion. Importantly, there is a lack of diabetes therapeutics that can simultaneously address glucose dysregulation and β-cell damage.

[0003] Although exogenous insulin can be lifesaving, it cannot replicate the kinetics of endogenous insulin secretion. Under physiological conditions, insulin is secreted by pancreatic β-cells in response to elevated blood glucose and accumulates in the liver via the portal vein. This dynamic process ensures postprandial glycemic control and systemic glucose homeostasis. The liver not only serves as a target organ to regulate glycogen synthesis and gluconeogenesis but also as a regulatory organ to regulate systemic insulin distribution. Transdermal administration bypasses the portal system, leading to systemic hyperinsulinemia, the risk of hypoglycemia, and weight gain, all of which accelerate β-cell depletion. In contrast, oral insulin, which utilizes the portal venous circulation to restore hepatic insulin signaling, is a promising alternative. However, the intestinal absorption barrier poses a significant challenge to improving the bioavailability of oral insulin. The harsh environment of the gastrointestinal tract (low pH and proteases) can easily destroy the structure of insulin, and the mucus layer on the surface of intestinal epithelial cells restricts the diffusion of insulin within the mucus. In particular, the intestinal epithelial cell layer is the most critical barrier to insulin entry into the systemic circulation, hindered by factors such as a lack of transport pathways, lysosomal degradation, and spatial restrictions of tight junctions. Among them, the receptor-mediated intestinal epithelial cell pathway provides a promising approach for targeted delivery. Sodium deoxycholate-modified carriers can deliver drugs directly to the liver via the portal vein, thereby increasing therapeutic concentrations in the liver while achieving intestinal permeability and liver targeting.

[0004] Furthermore, glucose-responsive insulin release systems can sense blood glucose levels and control insulin release. Under high blood glucose levels, accelerated insulin release rapidly lowers blood glucose; once blood glucose returns to normal, slower insulin release effectively prevents hypoglycemia. This system typically requires the integration of glucose-responsive components to achieve glucose-responsive insulin release, such as phenylboronic acid, glucose oxidase, and glucose-binding protein. Glucose oxidase, due to its high sensitivity, exhibits excellent glucose responsiveness.

[0005] Although related studies have produced liver-targeted glucose-responsive nanoparticles, such as patent CN115671050A, which uses polyacryloyl carbonate-polycaprolactone as raw materials and a phenylboronic acid derivative with a dihydroxy group to form a phenylboronic acid ester complex, these studies have overlooked the oxidative microenvironment that promotes β-cell death. Hyperglycemia-driven reactive oxygen species (ROS) activate the NF-κB-mediated inflammatory pathway, leading to a self-sustaining cycle of β-cell loss and systemic complications. Selenium, an essential trace element for antioxidant enzymes such as glutathione peroxidase (GPx), has been shown to have preclinical efficacy in reducing ROS. A treatment model that combines intelligent blood glucose regulation with reversal of pancreatic metabolic function could disrupt the progression of T2DM at its source.

[0006] Therefore, oral insulin delivery systems urgently need to improve the root cause of diabetes progression. This can be achieved by mimicking endogenous insulin dynamics to maintain blood glucose homeostasis and prevent β-cell apoptosis. At the same time, the system needs to be easy to prepare and carry, and improve the efficacy of diabetes treatment. Summary of the Invention

[0007] The purpose of the present invention is to overcome the above-mentioned defects of the prior art, and to provide an organic mesoporous silica nanoparticle for blood sugar stabilization and β-cell recovery, as well as a preparation method and application thereof, aiming to achieve glucose homeostasis and β-cell regeneration, and provide a safe, effective and revolutionary oral drug delivery method for diabetes treatment; 1) Oral functionalized organic silica nanoparticles simulate the mode of action of endogenous insulin, maintain blood sugar stability without the risk of hypoglycemia, and improve patient compliance; 2) Upregulate antioxidant selenoproteins, quench oxidative stress and inhibit inflammation; 3) The dual effects of antioxidant and anti-inflammatory can prevent β-cell damage, restore endogenous insulin secretion, and thus delay or even reverse the course of diabetes.

[0008] The purpose of the present invention is to provide oral organic mesoporous silica nanoparticles for blood sugar stabilization and β-cell recovery. Its glucose-responsive release mechanism includes that when in a hyperglycemic environment, H2O2 catalyzed by glucose oxidase triggers the breakage of Se-Se bonds and releases insulin, and the release rate is 3-8 times higher than that of normal blood sugar levels; its β-cell recovery function includes that selenium metabolites produced by the decomposition of Se-Se bonds upregulate glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), inhibit the NF-κB inflammatory pathway, reduce β-cell damage, and thus gradually restore β-cell function.

[0009] To achieve the above object, the technical solution of the present invention is as follows:

[0010] Disclosed are organic mesoporous silica nanoparticles for stabilizing blood sugar and restoring beta cells. The organic mesoporous silica nanoparticles comprise an inner core and a coating layer coated on the inner core; the coating layer comprises a transferrin coating (Tf) coated on the inner core and a deoxycholic acid modification layer (Dc) coated on the transferrin coating; the inner core comprises insulin, glucose oxidase (GOx), and an amino-modified organic mesoporous silica nanocarrier (MON); the transferrin coating is used to prevent drug leakage and gastrointestinal enzyme degradation, and the deoxycholic acid modification layer is used to enhance intestinal permeability and achieve liver-targeted delivery.

[0011] Optionally, in terms of mass percentage, the organic mesoporous silicon nanoparticles include 78% to 81% of the kernel, 13% ~17% transferrin coating and 5%~6% deoxycholic acid modified layer ; wherein, the mass ratio of the amino-modified organic mesoporous silica nanocarrier, insulin and glucose oxidase in the core is 12 to 24:5:1.

[0012] Optionally, the organic mesoporous silicon nanoparticles have a particle size of 90 nm to 150 nm, preferably 100 nm to 130 nm, a drug loading of 20% to 40%, and a potential of -5 mV to +10 mV, preferably 0 mV to +5 mV.

[0013] Optionally, the transferrin coating is covalently bonded to the surface of the amino-modified organic mesoporous silica nanocarrier via a carboxyl-amino reaction mediated by EDC / NHS.

[0014] Optionally, the deoxycholic acid modified layer is covalently bonded to the transferrin coating surface via an EDC / NHS-mediated carboxyl-amino reaction.

[0015] Optionally, the material of the deoxycholic acid modified layer includes one of sodium chenodeoxycholate, sodium ursodeoxycholate, sodium tauroursodeoxycholate, sodium glycocholate and sodium glycochenodeoxycholate.

[0016] The present invention also discloses a method for preparing the organic mesoporous silicon nanoparticles for stabilizing blood sugar and restoring β cells, comprising the following steps:

[0017] Step 1: Preparation of the core;

[0018] Step 2: modification of transferrin;

[0019] Step 3: Modification of deoxycholic acid.

[0020] Optionally, in step 1, the preparation method of the core MON@Peptide (MOP) is as follows:

[0021] (1) Dissolve cetyltrimethylammonium chloride (CTAT) in deionized water. To the obtained hexadecyltrimethylammonium chloride ( CTAT ) in aqueous solution Add triethanolamine dropwise (TEAH3), stirred at 75-85°C (preferably 80°C) for 20-40 min (preferably 30 min), then a mixture containing tetraethyl orthosilicate (TEOS) and bis[3-(triethoxysilyl)propyl]diallyl ether (BTESePD) was added dropwise, and stirring was continued at 75-85°C (preferably 80°C) for 3-4 h (preferably 4 h), and the product was collected by centrifugation and washed with ethanol;

[0022] (2) dispersing the product obtained in step (1) in ethanol at a concentration of 2.5 mg / mL, stirring at 75-85° C. (preferably 80° C.) for 3-4 h (preferably 4 h), cooling to room temperature, adding an amination reagent, and continuing to reflux at 75-85° C. (preferably 80° C.) for 12-16 h (preferably 12 h), collecting the precipitate by centrifugation and washing, and refluxing in an ethanol solution of ammonium nitrate (1% w / v) for 16 h, washing, and drying to obtain an amination-modified organic mesoporous silica nanocarrier MON;

[0023] (3) The amino-modified organic mesoporous silica nanocarrier is dispersed in a phosphate buffer solution with a pH of 7.4, and an insulin solution and a glucose oxidase solution are added. The mixture is stirred for 12 to 24 hours, and the unbound drug is removed by centrifugation and washing to obtain the core MON@Peptide (MOP).

[0024] Optionally, in step (1), the concentration of the CTAT aqueous solution is 0.01 to 0.02 g / mL, preferably 0.015 g / mL; the mass ratio of CTAT to TEAH3 is 3:1 to 5:1, preferably 4:1; the mass ratio of TEOS to BTESePD is 4:1 to 2:1, preferably 3:1; the mass ratio of CTAT to TEOS is 1:4 to 1:6, preferably 1:5.

[0025] Optionally, in step (2), the amination reagent includes one of 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane and N-(2-aminoethyl)-3-aminopropyltrimethoxysilane; the amount of the amination reagent added is 5% to 15% of the total mass of the silicon source, preferably 8% to 13%, and more preferably 10%.

[0026] Optionally, in step (3), the mass ratio of MON, insulin and glucose oxidase in the inner core MOP is 12 to 24:5:1, preferably 18 to 24:5:1, and more preferably 20:5:1.

[0027] Optionally, in step 2, the transferrin modification method includes: mixing a transferrin solution, EDC and NHS, adding the mixture dropwise to the drug-loaded core MOP dispersion, stirring the reaction for 12 to 24 hours, and collecting the transferrin-modified nanoparticles MOP@T by centrifugation; wherein the mass ratio of the amino-modified organic mesoporous silica nanocarrier MON to the transferrin is 20 to 40:1, preferably 25:1; the mass ratio of the transferrin, EDC and NHS is 2:1 to 2:1 to 2, preferably 2:1:1.

[0028] Optionally, in step three, the deoxycholic acid modification method includes: mixing a deoxycholic acid solution, EDC and NHS, adding the mixture dropwise to the MOP@T dispersion, stirring for 12 hours to 24 hours, and collecting by centrifugation to obtain the organic mesoporous silicon nanoparticles MOP@T@D; wherein the mass ratio of the amino-modified organic mesoporous silicon nanocarrier MON to deoxycholic acid is 40 to 60:1, preferably 50:1; the mass ratio of deoxycholic acid, EDC and NHS is 2:1 to 2:1 to 2, preferably 2:1:1.

[0029] Optionally, the centrifugal washing condition is 8000 rpm to 12000 rpm, preferably 10000 rpm, and lasts for 10 min to 20 min, preferably 15 min.

[0030] The present invention also discloses an application of the organic mesoporous silicon nanoparticles for stabilizing blood sugar and restoring beta cells in the preparation of a drug delivery system.

[0031] The present invention also discloses a use of the organic mesoporous silicon nanoparticles for stabilizing blood sugar and restoring beta cells in the preparation of oral administration.

[0032] The system of the present invention has excellent ability to maintain blood sugar stability, can significantly increase the level of antioxidant enzymes in rats and decrease the level of inflammatory factors. After 4 weeks of treatment, the insulin secretion level of rats is significantly improved compared with the model group.

[0033] The implementation of the present invention will have the following beneficial effects:

[0034] The oral organic mesoporous silicon nanoparticles for blood sugar stabilization and beta cell recovery provided by the present invention improve the intestinal permeability and liver targeting of the insulin delivery system; under high blood sugar, H2O2 generated by glucose oxidase (GOx) can trigger the cleavage of the diselenide bond and release insulin on demand, which can achieve an oral hypoglycemic effect of more than 12 hours in diabetic rats and avoid the risk of hypoglycemia. At the same time, the selenium derivatives of the nanoparticles gradually increase the level of selenium-containing antioxidant enzymes, which can inhibit oxidative stress and NF-κB-mediated inflammation. The present invention significantly reduces beta cell apoptosis and significantly restores the insulin secretion function of beta cells. The oral organic mesoporous silicon nanoparticles for blood sugar stabilization and beta cell recovery of the present invention and their applications not only solve the pathological driving factors of type 2 diabetes, but also the preparation method is simple to operate, the conditions are mild, and have broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 In vitro characterization of nanoparticles before and after drug loading.

[0036] Figure 2 This is the in vitro glucose-responsive release characteristic diagram of MOP@T@D.

[0037] Figure 3 Figure 3 shows the intestinal permeability and liver targeting distribution of MOP@T@D.

[0038] Figure 4 This is the pharmacodynamic diagram and oral glucose tolerance diagram of MOP@T@D based on diabetic rats.

[0039] Figure 5 This is the efficacy diagram of MOP@T@D in anti-inflammatory, antioxidant and pancreatic β-cell function recovery in diabetic rats. DETAILED DESCRIPTION

[0040] The principles and features of the present invention are described below in conjunction with the examples. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention. Where specific conditions are not specified in the examples, they are carried out according to conventional conditions or conditions recommended by the manufacturer. In particular, bis[3-(triethoxysilyl)propyl]diallyl ether (BTESePD) was synthesized with reference to existing methods. Reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0041] Example 1 Preparation of organic mesoporous silicon nanoparticles for blood sugar stabilization and β-cell recovery

[0042] A. Preparation of Aminated Organic Mesoporous Silica Nanocarriers (MON)

[0043] Biodegradable silica nanoparticles were prepared by a sol-gel method using tetraethyl orthosilicate (TEOS) and bis[3-(triethoxysilyl)propyl] diallyl ether as silicon sources. 0.6 g of CTAT and 0.15 g of triethanolamine were dissolved in 40 mL of deionized water and stirred at 80°C for 30 minutes. Then, 4.0 g of TEOS and 1.0 g of BTESePD were added dropwise, and the mixture was stirred at 80°C for 4 hours. The product was collected by centrifugation and washed three times with ethanol. The product was dispersed in ethanol at a concentration of 2.5 mg / mL, stirred at 80°C for 3 hours, cooled to room temperature, and 0.5 mL of APTES was added. The mixture was refluxed at 80°C for another 12 hours. The precipitate was collected by centrifugation and washed. MON was then refluxed in a 1% w / v ammonium nitrate solution in ethanol for 16 hours, washed, and dried.

[0044] B. Insulin and glucose oxidase loading

[0045] 40 mg of MON was ultrasonically dispersed in 20 mL of PBS buffer (pH 7.4), followed by the addition of insulin (10 mg, 10 mg / mL) and glucose oxidase (2 mg, 1.0 mg / mL) solutions for drug loading. After stirring at room temperature for 12 h to ensure adequate loading, the resulting insulin- and glucose oxidase-loaded MOP nanoparticles were collected by centrifugation.

[0046] C. Modification of transferrin

[0047] A mixed solution of transferrin (2 mg), EDC (1.0 mg), and NHS (1.0 mg) was dropped into the MON dispersion and stirred for 24 h to obtain transferrin-coated MOP@T.

[0048] D. Modification of deoxycholic acid

[0049] A mixed solution of deoxycholic acid (1 mg), EDC (0.5 mg), and NHS (0.5 mg) was dropped into the MOP@T dispersion and stirred for 12 h to obtain MOP@T@D.

[0050] Example 2 Characterization of Nanoparticles

[0051] Dynamic light scattering was used to investigate the particle size potential of the nanoparticles before and after drug loading. Here, BTESePD was replaced with an equal amount of 1,6-bis(triethoxysilyl)hexane (BTESiH) and the same preparation method was used to obtain non-responsive mesoporous silica nanoparticles (MSP@T@D) for property comparison.

[0052] Dynamic light scattering results showed that the average size of MON was 90.3 nm and the Zeta potential was +15.5 mV ( Figure 1ab). The BET specific surface area of ​​MON obtained from the nitrogen adsorption-desorption isotherm is 386.6 m 2 / g, average pore size 9.2nm ( Figure 1 c). This large pore size is beneficial to improve the loading efficiency of insulin and glucose oxidase. Fourier transform infrared spectroscopy (FTIR) results confirmed the presence of Se-Se bonds in the mesoporous framework (550-750 cm -1 ) in the inclusion ( Figure 1 d).

[0053] After transferrin modification, the particle size of MOP@T increased to 136.6±16nm, and the Zeta potential shifted to 24.1±3.1mV ( Figure 1 b). Subsequent modification with deoxycholic acid reduced the particle size to 120.1±3.2 nm, and the zeta potential was nearly neutral (3.2±1.45 mV), indicating that deoxycholic acid reduced the thickness of the surface hydration layer of the nanoparticles and effectively neutralized the excess positive charge on the surface. Compared with MOP@T@D, the loading of insulin and GOx had little effect on the particle size of MOP@T@D ( Figure 1 e).

[0054] Example 3 Glucose-responsive release characteristics of MOP@T@D

[0055] The morphology of MOP@T@D in 100 and 400 mg / dL glucose media was examined by TEM. The release of MOP@T@D in PBS containing different glucose concentrations (0, 100, 200, 300, and 400 mg / dL) was evaluated. Furthermore, the insulin release from MOP@T@D during alternating cycles of different glucose concentrations (100, 200, and 400 mg / dL) was also investigated.

[0056] TEM results showed that MOP@T@D showed structural collapse in high blood sugar environment and broke into irregular fragments after 72 hours, while the skeleton decomposed slowly in low blood sugar environment ( Figure 2 a), whereas the presence of glucose did not affect the structure of MSP@T@D, confirming that high blood sugar conditions can trigger the degradation of MOP@T@D.

[0057] The release profiles of MOP@T@D at different glucose concentrations showed that at normal blood glucose (100 mg / dL), the amount of insulin released was still minimal, while high blood glucose (400 mg / dL) accelerated the release rate by 3.2 times ( Figure 2 b).

[0058] In a simulated postprandial glucose fluctuation model, alternating exposure to hypoglycemic and hyperglycemic conditions induces a pulsatile release of insulin ( Figure 2c) is very similar to the glucose-responsive insulin secretion of pancreatic β cells. This responsive behavior ensures the suppression of insulin release during hypoglycemia and allows for rapid correction of blood glucose.

[0059] Example 4 Highly efficient intestinal permeation and liver-targeted distribution of MOP@T@D

[0060] Fasting healthy male Sprague-Dawley rats were anesthetized, and a 3 cm ileum was ligated. Dual fluorescently labeled nanoparticles (FITC-insulin and Cy5-MON) were then injected. After a 1-hour incubation, frozen sections of the ileum were prepared and observed using CLSM. Four hours after oral administration, fluorescence imaging of vital organs was performed using a small animal in vivo imaging system.

[0061] In situ confocal imaging of rat ileum sections showed that dual-labeled MOP@T@D successfully escaped from mucus and was subsequently absorbed by villi ( Figure 3 a). In vivo imaging results showed that MOP@T@D preferentially accumulated in the liver ( Figure 3 b) This liver targeting reflects physiological insulin transport through the portal vein, favoring MOP@T@D to directly regulate hepatic glucose utilization.

[0062] Example 5: Efficacy of MOP@T@D in Improving Oral Insulin Bioavailability and Glucose Homeostasis

[0063] The animal model used in the experiment was a T2DM rat model: SD rats were adaptively fed for one week and then fed a high-fat diet for eight weeks. Afterward, the mice were fasted for 6 hours and then intraperitoneally injected with 35 mg / kg of STZ for five consecutive days. Random blood glucose levels were monitored 72 hours after injection, and a random blood glucose level greater than 16.8 mmol / L was considered successful. The diabetic rats were randomly divided into six groups. Five groups received oral administration of insulin solution, MOP, MOP@T, MSP@T@D, and MOP@T@D (80 IU / kg), respectively. The final group received subcutaneous insulin injection (5 IU / kg). Blood glucose levels were measured at different time points after administration using a glucometer. Three hours after administration, the rats were gavaged with 2 g / kg of glucose solution for an oral glucose tolerance test.

[0064] Compared with MOP and MOP@T, MOP@T@D caused the greatest reduction in blood glucose levels in diabetic rats, and the effect lasted for more than 12 h ( Figure 4 a). In the oral glucose tolerance test (OGTT), MOP@T@D restored normoglycemia within 1 h ( Figure 4 b), demonstrating the ability of MOP@T@D to maintain blood glucose stability.

[0065] Example 6: MOP@T@D restores pancreatic β-cell function through anti-inflammatory and antioxidant effects

[0066] After four weeks of subcutaneous insulin injection (5 IU / kg) or oral administration of MOP, MOP@T, MSP@T@D, and MOP@T@D (80 IU / kg), MOP@T@D increased the activities of glutathione peroxidase (Gpx) and superoxide dismutase (SOD) in diabetic rats. Figure 5 a,b), while reducing lipid peroxidation ( Figure 5 c). Compared with the model group, the MOP@T@D group reduced TNF-α by 53%, IL-6 by 59%, and IL-1β by 49% ( Figure 5 df). Histomorphometric analysis showed that MOP@T@D treatment significantly enlarged the pancreatic islet area ( Figure 5 g), and the insulin secretion level of the pancreatic islets also approaches the normal physiological level ( Figure 5 h). Crucially, the therapeutic effects of MOP@T@D persisted after treatment. Seven days after drug withdrawal, rats treated with MOP@T@D maintained normoglycemia, while rats treated with MOP@T@D returned to hyperglycemia ( Figure 5 i) MOP@T@D can provide new possibilities for restoring pancreatic β-cell function by combating oxidative stress and inflammation.

[0067] The above-described embodiments merely represent several implementation methods of the present invention. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that a person skilled in the art would be able to make various modifications and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. An organic mesoporous silicon nanoparticle for blood sugar stabilization and β-cell recovery, characterized in that: The organic mesoporous silicon nanoparticles include a core and a coating layer coated on the surface of the core; The coating layer is composed of a transferrin coating layer coated on the surface of the core and a deoxycholic acid modified layer coated on the surface of the transferrin coating layer; The core is composed of insulin, glucose oxidase and amino-modified organic mesoporous silica nanocarriers; The transferrin coating is used to prevent drug leakage and gastrointestinal enzyme degradation, and the deoxycholic acid modified layer is used to enhance intestinal permeability and achieve liver-targeted delivery.

2. The organic mesoporous silicon nanoparticles for blood sugar stabilization and β-cell recovery according to claim 1, characterized in that: In terms of mass percentage, the organic mesoporous silicon nanoparticles Including 78% to 81% of the core, 13% to 17% of the transfer iron Protein coating and 5% to 6% deoxycholic acid modification layer; Wherein, the mass ratio of the amino-modified organic mesoporous silicon nanocarrier, insulin and glucose oxidase in the inner core is 12-24:5:

1.

3. The organic mesoporous silicon nanoparticles for blood sugar stabilization and β-cell recovery according to claim 1, characterized in that: The particle size of the organic mesoporous silicon nanoparticles is 90nm-150nm, and the drug loading amount is 20%-40%.

4. The organic mesoporous silicon nanoparticles for blood sugar stabilization and β-cell recovery according to claim 1, characterized in that: The transferrin coating is covalently bonded to the surface of the amino-modified organic mesoporous silica nanocarrier through an EDC / NHS-mediated carboxyl-amino reaction; The deoxycholic acid modified layer is covalently bonded to the transferrin coating surface through an EDC / NHS-mediated carboxyl-amino reaction; The material of the deoxycholic acid modified layer includes one of sodium chenodeoxycholate, sodium ursodeoxycholate, sodium tauroursodeoxycholate, sodium glycocholate and sodium glycochenodeoxycholate.

5. A method for preparing organic mesoporous silicon nanoparticles for blood sugar stabilization and β-cell recovery according to any one of claims 1 to 4, characterized in that: The following steps are involved: Step 1: Preparation of the core; Step 2: modification of transferrin; Step 3: Modification of deoxycholic acid.

6. The preparation method according to claim 5, characterized in that In step 1, the preparation method of the core MON@Peptide is as follows: (1) Dissolve hexadecyltrimethylammonium chloride in deionized water, add triethanolamine dropwise to the obtained aqueous solution of hexadecyltrimethylammonium chloride, stir at 75-85°C for 20-40 minutes, then add dropwise a mixture of ethyl orthosilicate and bis[3-(triethoxysilyl)propyl]diallyl ether, continue stirring at 75-85°C for 3-4 hours, collect the product by centrifugation and wash with ethanol; (2) dispersing the product obtained in step (1) in ethanol at a concentration of 2.5 mg / mL, stirring at 75-85° C. for 3-4 hours, cooling to room temperature, adding an amination reagent, and continuing to reflux at 75-85° C. for 12-16 hours. Collecting the precipitate by centrifugation and washing it, and refluxing it in an ethanolic solution of ammonium nitrate for 16 hours. After washing and drying, the amination-modified organic mesoporous silica nanocarrier MON is obtained. (3) dispersing the amino-modified organic mesoporous silica nanocarrier MON in a phosphate buffer solution with a pH of 7.4, adding an insulin solution and a glucose oxidase solution, stirring for 12 h to 24 h, and removing unbound drugs by centrifugation and washing to obtain the core MON@Peptide; Wherein, in step (1), the concentration of the aqueous solution of hexadecyltrimethylammonium chloride is 0.01-0.02 g / mL; the mass ratio of hexadecyltrimethylammonium chloride to triethanolamine is 3:1-5:1; the mass ratio of ethyl orthosilicate to bis[3-(triethoxysilyl)propyl]diallyl ether is 4:1-2:1; the mass ratio of hexadecyltrimethylammonium chloride to ethyl orthosilicate is 1:4-1:6; In step (2), the amination reagent includes one of 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane and N-(2-aminoethyl)-3-aminopropyltrimethoxysilane; the amount of the amination reagent added is 5% to 15% of the total mass of the silicon source; In step (3), the mass ratio of the amino-modified organic mesoporous silica nanocarrier, insulin and glucose oxidase in the inner core MON@Peptide is 12 to 24:5:

1.

7. The preparation method according to claim 5, characterized in that In step 2, the transferrin modification method includes: The transferrin solution, EDC and NHS were mixed and added dropwise to the core MON@Peptide dispersion, stirred for 12 to 24 hours, and the transferrin-modified nanoparticles MOP@T were collected by centrifugation. The mass ratio of the amino-modified organic mesoporous silica nanocarrier MON to the transferrin is 20-40:1; the mass ratio of the transferrin, EDC and NHS is 2:1-2:1-2.

8. The preparation method according to claim 7, characterized in that In step 3, the modification method of deoxycholic acid includes: Mixing deoxycholic acid solution, EDC and NHS, and adding the mixture dropwise to the MOP@T dispersion, stirring and reacting for 12 to 24 hours, and collecting the mixture by centrifugation to obtain the organic mesoporous silicon nanoparticles MOP@T@D; The mass ratio of the amino-modified organic mesoporous silica nanocarrier MON to deoxycholic acid is 40-60:1; the mass ratio of deoxycholic acid, EDC and NHS is 2:1-2:1-2.

9. Use of the organic mesoporous silicon nanoparticles for blood sugar stabilization and β-cell recovery according to any one of claims 1 to 5 in the preparation of a drug delivery system.

10. Use of the organic mesoporous silicon nanoparticles for blood sugar stabilization and β-cell recovery according to any one of claims 1 to 5 in the preparation of oral administration.

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