Treg exosome selenium tungsten nano delivery system, and preparation method and application thereof

Abstract

The application relates to the biomedical field, in particular to a Treg exosome selenium tungsten nano delivery system and a preparation method and application thereof. The Treg exosome selenium tungsten nano delivery system comprises Treg-derived exosomes, chitosan, selenium nanoparticles, hexavalent tungsten and sodium alginate; the chitosan is combined with the Treg-derived exosomes to form a composite carrier; the selenium nanoparticles and the hexavalent tungsten are independently co-loaded on the composite carrier, wherein selenium in the selenium nanoparticles is formed in situ by reduction, and the loaded tungsten exists in the form of hexavalent; and the sodium alginate is coated on the outer layer of the composite carrier loaded with the selenium nanoparticles and the hexavalent tungsten to form an oral delivery system. The Treg exosome selenium tungsten nano delivery system can realize the enhancement of the immunotherapy effect, the regulation of an inflammatory microenvironment, the recovery of immune homeostasis and the maintenance of intestinal flora balance.

Description

Technical Field

[0001] This application relates to the field of biomedical technology, and in particular to the Treg exosome selenium-tungsten nanodelivery system, its preparation method and application. Background Technology

[0002] Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by persistent inflammation of the colonic mucosa. Its development involves multiple pathological processes, including intestinal oxidative stress imbalance, disruption of immune homeostasis, and gut microbiota dysbiosis. Currently, clinical treatment primarily utilizes aminosalicylic acid derivatives, glucocorticoids, biologics, and immunosuppressants.

[0003] However, due to the complex pathological mechanisms, multifactorial driving force, and high recurrence rate of UC, existing treatment strategies are difficult to achieve comprehensive regulation of the inflammatory microenvironment, immune abnormalities, and microbial imbalance. Long-term treatment still faces problems such as limited efficacy, increased risk of immunosuppression-related infections, and disease recurrence.

[0004] Furthermore, elevated levels of intestinal oxidative stress are a significant pathological factor in the development and progression of ulcerative colitis (UC). Inflammatory stimuli induce the production of large amounts of reactive oxygen species (ROS), which can further damage the intestinal epithelial barrier and promote inflammatory cascade responses. Meanwhile, the maintenance of gut microbiota homeostasis depends on a complex metabolic regulatory network, in which the growth and metabolic processes of some bacteria rely on the molybdenum cofactor-related enzyme system.

[0005] Therefore, it is of great significance to develop novel products that can enhance the efficacy of immunotherapy while also regulating the inflammatory microenvironment, restoring immune homeostasis, and maintaining gut microbiota balance. Summary of the Invention

[0006] In order to enhance the efficacy of immunotherapy while regulating the inflammatory microenvironment, restoring immune homeostasis and maintaining gut microbiota balance, this application provides a Treg exosome selenium-tungsten nanodelivery system, its preparation method and application.

[0007] In a first aspect, this application provides a Treg exosome selenium-tungsten nanodelivery system, which adopts the following technical solution:

[0008] A Treg exosome selenium-tungsten nanodelivery system includes Treg-derived exosomes, chitosan, selenium nanoparticles, hexavalent tungsten, and sodium alginate;

[0009] Chitosan and Treg-derived exosomes combine to form a composite carrier; selenium nanoparticles and hexavalent tungsten are independently co-loaded on the composite carrier, wherein the selenium in the selenium nanoparticles is formed by in-situ reduction, and the loaded tungsten exists in the hexavalent form;

[0010] Sodium alginate is coated onto the outer layer of a composite carrier loaded with selenium nanoparticles and hexavalent tungsten to form an oral delivery system.

[0011] By employing the above technical solutions, firstly, Treg-derived exosomes, as natural immunomodulatory carriers, are rich in various anti-inflammatory factors and immunosuppressive signaling molecules, and can exert anti-inflammatory and immunomodulatory effects by inhibiting pro-inflammatory signaling pathways, promoting macrophage M2 polarization, and restoring the Treg / Th17 cell balance. Secondly, selenium nanoparticles have excellent antioxidant properties and can efficiently scavenge excess reactive oxygen species (ROS) in the inflammatory microenvironment by participating in the synthesis of selenoproteins GPX2 and TXNRD1, thus alleviating oxidative stress damage. Tungsten, by competitively replacing molybdenum in the molybdenum cofactor, selectively inhibits the activity of molybdenum enzymes dependent on Enterobacteriaceae, thereby inhibiting the abnormal proliferation of opportunistic pathogens during inflammation. The sodium alginate outer coating endows the system with oral delivery capability, and can utilize the property of sodium alginate being insoluble in gastric acid but soluble in the intestine to achieve colon-targeted delivery. Therefore, this application achieves multi-level synergistic intervention on the complex pathological mechanism of ulcerative colitis by organically integrating the four functions of "immune regulation-ROS clearance-microbiota regulation-oral targeting", overcoming the problem that a single treatment strategy cannot take into account the comprehensive regulation of immune abnormalities, oxidative stress and microbiota imbalance.

[0012] Furthermore, the molar ratio of selenium to hexavalent tungsten in the selenium nanoparticles is 1:(0.5-2).

[0013] By employing the above technical solution and optimizing the stoichiometric ratio of selenium to tungsten, the optimal synergistic effect of the two functional components on the composite carrier is ensured. Sufficient selenium dosage is required to exert its ROS scavenging and antioxidant functions, while an appropriate dosage of tungsten is needed to effectively inhibit the molybdenum enzyme activity of Enterobacteriaceae. When the selenium-tungsten molar ratio is within this range, it ensures both the efficient scavenging of excess ROS from inflammatory sites by selenium nanoparticles and the sufficient inhibition of opportunistic pathogenic metabolic pathways by tungsten, while avoiding potential toxicity or functional interference from excessive amounts of either component, thus achieving the optimal balance between antioxidant and gut microbiota regulation functions.

[0014] Furthermore, the molar ratio of selenium to hexavalent tungsten in the selenium nanoparticles is 1:1.

[0015] Furthermore, the mass ratio of chitosan to Treg-derived exosomes is 1:(1-3).

[0016] By employing the above technical solution, chitosan, as a cationic polymer, can bind to negatively charged exosome membranes through electrostatic interactions, forming a stable composite carrier structure. When the mass ratio of exosomes to chitosan is within this range, it ensures that sufficient chitosan can effectively encapsulate and protect the exosomes, preventing their degradation and inactivation in the gastrointestinal environment, while avoiding excessive chitosan leading to overly large composite carrier particle sizes that would affect delivery efficiency and mucosal penetration. An appropriate chitosan ratio also provides sufficient binding sites for the subsequent coordination loading of selenium and tungsten ions, ensuring efficient loading of the metal functional components.

[0017] Furthermore, the Treg-derived exosomes are derived from induced regulatory T cells or natural regulatory T cells.

[0018] Secondly, this application provides a method for preparing a Treg exosome selenium-tungsten nanodelivery system, employing the following technical solution:

[0019] A method for preparing a Treg exosome selenium-tungsten nanodelivery system includes the following steps:

[0020] S1. Preparation of exosome-chitosan composite carrier: Chitosan was dissolved in acetic acid to obtain a chitosan solution, and Treg-derived exosomes were added and mixed. The pH was adjusted to allow the chitosan to bind with the exosomes to form an exosome-chitosan composite carrier.

[0021] Loading and reduction of S2.Se and W mixed metal ions: Selenite and tungstate were introduced into the composite support system obtained in S1 for coordination loading, and then ascorbic acid was added for in-situ reduction, so that selenite was reduced in-situ to selenium nanoparticles and loaded on the composite support, and tungsten was independently loaded on the composite support in hexavalent form, thus obtaining a composite support loaded with selenium nanoparticles and hexavalent tungsten.

[0022] S3. Preparation of oral metal nanoparticle delivery system: Sodium alginate solution is mixed with the system obtained in S2 to coat the outer layer of the composite carrier with sodium alginate, thereby obtaining the oral delivery system.

[0023] By adopting the above technical solution, firstly, step S1 adjusts the pH to allow chitosan to bind with exosomes. The cationic properties of chitosan and the negative charge on the exosome surface form a stable composite carrier. The operating conditions are mild and do not damage the natural structure and biological activity of the exosomes. Secondly, step S2 employs a "coordination loading followed by in-situ reduction" strategy: selenite and tungstate are first loaded onto the composite carrier through coordination, then ascorbic acid is added for in-situ reduction. This reduces selenite to elemental selenium nanoparticles, which are then firmly loaded onto the carrier, and reduces tungsten in the tungstate to hexavalent tungsten.

[0024] In-situ reduction refers to the direct addition of selenite and tungstate to the pre-formed exosome-chitosan composite carrier, followed by the use of ascorbic acid as a reducing agent. This allows the selenite to be reduced in situ to selenium nanoparticles, which are then loaded onto the composite carrier. This in-situ reduction method avoids the complex operation of reloading pre-synthesized nanoparticles, ensuring uniform distribution and stable loading of selenium nanoparticles on the carrier. Finally, step S3 involves encapsulation with sodium alginate to form an oral delivery system, utilizing the colon-targeting properties of sodium alginate for oral administration. The entire preparation method is simple, operates under mild conditions, and exhibits good reproducibility, making it suitable for large-scale production.

[0025] Furthermore, the concentration of the chitosan solution in S1 is 5-10 mg / mL.

[0026] By employing the above technical solution, a suitable chitosan concentration ensures its complete dissolution in acetic acid and the formation of a homogeneous solution system, providing a favorable reaction environment for subsequent effective binding with exosomes. When the chitosan concentration is within this range, the solution viscosity is moderate, which is beneficial for the unfolding of chitosan molecular chains and sufficient contact with the exosome surface, while avoiding excessive viscosity due to excessive concentration, which would affect the mixing uniformity and the formation efficiency of the composite carrier. This concentration range also matches the loading of metal ions and the reduction reaction conditions in subsequent steps, helping to ensure the stability and batch-to-batch consistency of the entire preparation process.

[0027] Furthermore, in S2, the selenite is sodium selenite with a concentration of 0.5 mM; the tungstate is sodium tungstate with a concentration of 0.5 mM; and the ascorbic acid has a concentration of 30 mM.

[0028] By employing the above-mentioned technical solution, sodium selenite and sodium tungstate are common and inexpensive metal salt precursors with good solubility and stability in water, facilitating precise control of the dosage ratio. The 0.5 mM concentration setting matches the aforementioned 1:1 selenium-tungsten molar ratio, ensuring a balanced loading of the two functional components on the composite carrier. 30 mM ascorbic acid serves as a mild reducing agent, reducing selenite to selenium nanoparticles and tungsten in tungstate to hexavalent tungsten under mild conditions without affecting exosome bioactivity. This reduction system avoids the toxicity and side reactions that may result from using strong reducing agents, ensuring the biosafety of the delivery system.

[0029] Furthermore, the in-situ reduction temperature in S2 is 30-40℃, the incubation time for the coordination load is 1-3h, and the in-situ reduction incubation time is 1-3h.

[0030] Thirdly, this application provides the use of a Treg exosome selenium-tungsten nanodelivery system in the preparation of a medicament for treating ulcerative colitis.

[0031] In summary, this application has the following beneficial effects:

[0032] 1. This application utilizes Treg exosomes as a natural immunomodulatory carrier, which improves the biocompatibility and immunomodulatory capacity of the delivery system and can effectively alleviate the local inflammatory response of UC;

[0033] 2. This application achieves efficient removal of excess ROS in the inflammatory microenvironment by introducing Se nanoparticles, thereby reducing oxidative stress-mediated intestinal epithelial damage;

[0034] 3. This application regulates bacterial metabolic processes by introducing W element, thereby enhancing the effect of immunotherapy while inhibiting the abnormal proliferation of opportunistic pathogens and reducing the risk of bacterial dysbiosis caused by immunosuppressive therapy;

[0035] 4. This application establishes a multifunctional synergistic treatment strategy of "ROS elimination-microbiota regulation-immune remodeling", providing a new technical solution for nanoimmunotherapy of ulcerative colitis. Attached Figure Description

[0036] Figure 1 Electron microscopy images for morphological characterization; where a is a transmission electron microscope image of TExo; b is a transmission electron microscope image of TExo@Se / W;

[0037] Figure 2 For the product DLS particle size and Zeta potential;

[0038] Figure 3 The image is used to illustrate the anti-inflammatory effect.

[0039] Figure 4 The diagram illustrates the effectiveness of ROS removal.

[0040] Figure 5 for Figure 4 The quantification results graph;

[0041] Figure 6 To illustrate the antibacterial effect of bacterial colonies;

[0042] Figure 7 for Figure 6 The quantification results graph;

[0043] Figure 8 This is a diagram of a mouse model of DSS-induced acute colitis.

[0044] Figure 9 Images of mouse colon tissue after different treatments;

[0045] Figure 10 Colon length in mice after different treatments;

[0046] Figure 11 Image showing the results of H&E pathological staining;

[0047] Figure 12 A graph showing the colon injury scoring results;

[0048] Figure 13 Flow cytometry results of the proportion of Treg cells in colon tissue after treatment;

[0049] Figure 14 This represents the quantitative results of the proportion of Treg cells in the colon tissue after treatment. Detailed Implementation

[0050] The present application will be further described in detail below with reference to the embodiments.

[0051] raw material

[0052] It should be noted that: in the following examples, unless otherwise specified, the conditions shall be in accordance with conventional conditions or the manufacturer's recommended conditions; and the raw materials used in the following examples, unless otherwise specified, shall be from commercially available sources.

[0053] Chitosan: pharmaceutical grade, degree of deacetylation ≥95%, conforming to Chinese Pharmacopoeia standards;

[0054] Sodium alginate: pharmaceutical grade, conforming to Chinese Pharmacopoeia standards;

[0055] Sodium selenite: analytical grade;

[0056] Sodium tungstate (Na2WO4·2H2O): analytical grade;

[0057] Ascorbic acid: cell culture grade;

[0058] PBS: Phosphate Buffered Salt;

[0059] RAW 264.7: Mouse mononuclear macrophage leukemia cells;

[0060] LPS: Lipopolysaccharide (LPS);

[0061] DSS: Sodium dextran sulfate, colitis modeling grade, molecular weight 36,000-50,000 Da;

[0062] Treg-derived exosomes: extracted and prepared according to conventional methods in the art, such as by ultracentrifugation or exosome extraction kits, from the culture supernatant of induced regulatory T cells (iTreg) or natural regulatory T cells (nTreg);

[0063] Regulatory T cells (Tregs): These can be obtained from peripheral blood mononuclear cells (PBMCs) using an immunomagnetic bead sorting kit, or from naïve CD4 cells using conventional induction methods. + T cells were obtained through induction.

[0064] All other reagents were of analytical grade or cell culture grade.

[0065] Example

[0066] Example 1

[0067] A Treg exosome selenium-tungsten nanodelivery system, the preparation method of which is as follows:

[0068] S1. Preparation of exosome-chitosan composite carrier

[0069] Chitosan was dissolved in acetic acid to obtain a 7.5 mg / mL chitosan solution. Then, the chitosan and Treg-derived exosomes were thoroughly mixed at a mass ratio of 1:2. The pH of the solution was adjusted to 6-7 using NaOH, and the solution was centrifuged at 15,000 rpm for 0.5 h.

[0070] Loading and reduction of S2.Se and W mixed metal ions

[0071] Add 0.5 mM sodium tungstate and 0.5 mM sodium selenite to the mixture obtained in S1 for resuspension, incubate at 37°C for 2 h, add 30 mM ascorbic acid, mix and incubate at 37°C for 2 h, and centrifuge at 15000 rpm for 0.5 h.

[0072] S3. Preparation of oral metal nanoparticle delivery system

[0073] The precipitate was obtained by mixing sodium alginate solution with S2, stirring thoroughly with magnetic force, centrifuging at 15000 rpm for 0.5 h, removing the supernatant, resuspending the precipitate, and obtaining the final oral delivery system, denoted as TExo@Se / W.

[0074] Example 2

[0075] Unlike Example 1, in Example 2, the concentration of sodium tungstate in S2 is 0.25 mM and the concentration of sodium selenite is 0.5 mM, that is, the molar ratio of selenium to tungsten is 1:0.5.

[0076] Example 3

[0077] Unlike Example 1, in Example 3, the concentration of sodium tungstate in S2 is 1.0 mM and the concentration of sodium selenite is 0.5 mM, that is, the molar ratio of selenium to tungsten is 1:2.

[0078] Example 4

[0079] Unlike Example 1, in Example 4 the in-situ reduction temperature was 30°C, the incubation time for the coordination load was 3 hours, and the incubation time for the in-situ reduction was 3 hours.

[0080] Example 5

[0081] Unlike Example 1, in Example 5 the in-situ reduction temperature was 40°C, the incubation time for the coordination load was 1 hour, and the incubation time for the in-situ reduction was 1 hour.

[0082] Comparative Example

[0083] Comparative Example 1

[0084] Unlike Example 1, sodium selenite was not added in S2 of Comparative Example 1. Only 0.5 mM sodium tungstate was added for coordination loading, and ascorbic acid reduction treatment was not performed to obtain the Treg exosome tungsten nanodelivery system, denoted as TExo@W.

[0085] Comparative Example 2

[0086] Unlike Example 1, sodium tungstate was not added in S2 of Comparative Example 2. Instead, 0.5 mM sodium selenite was added for coordination loading, and 30 mM ascorbic acid was added for in-situ reduction. The remaining steps were the same as in Example 1, resulting in the Treg exosome selenium nanodelivery system, denoted as TExo@Se.

[0087] Comparative Example 3

[0088] Unlike Example 1, in Comparative Example 3, sodium selenite and sodium tungstate were not added in S2. The composite carrier precipitate was only resuspended with PBS buffer. Ascorbic acid reduction treatment was not performed, and sodium alginate coating in S3 was not performed, resulting in a simple Treg exosome chitosan composite delivery system.

[0089] Comparative Example 4

[0090] Unlike Example 1, in Comparative Example 4, sodium selenite and sodium tungstate were not added in S2. The composite carrier precipitate was resuspended with PBS buffer without ascorbic acid reduction treatment. Then, sodium alginate coating was directly performed in S3 to obtain an empty Treg exosome chitosan composite delivery system.

[0091] Performance testing

[0092] I. Characterization of TExo@Se / W

[0093] The morphology of TExo and TExo@Se / W was observed using transmission electron microscopy. Here, TExo is an unmodified natural Treg-derived exosome. (See...) Figure 1 It can be seen that both TExo and TExo@Se / W exhibit typical exosome-like cup vesicle structures, indicating that the loading of Se / W nanocomponents did not disrupt the basic structure of exosomes.

[0094] The DLS particle size and zeta potential of the delivery system were measured. The unmodified natural Treg-derived exosomes were denoted as TExo, and the product of Comparative Example 3 was denoted as TExo@CS. Following the method of Example 1, after centrifugation in step S2, the precipitate was collected to obtain the exosome-chitosan composite carrier loaded with selenium nanoparticles and hexavalent tungsten, denoted as TExo@CS-Se / W. The product of Example 1 was denoted as TExo@CS-Se / W-SA. The DLS particle size and zeta potential of the above products are shown in [reference needed]. Figure 2 The increasing particle size at each step confirms the existence of a functional layer on the exosome surface: the significant increase in particle size after chitosan binding indicates that cationic chitosan successfully encapsulates the exosome surface through electrostatic adsorption; the further increase in particle size after Se / W in-situ loading demonstrates that the metal nanoparticles are indeed successfully anchored and grown on or inside the composite carrier; and the continued increase in particle size after sodium alginate coating indicates the successful formation of the outer coating layer. Simultaneously, the gradual shift of the zeta potential from negative to positive and back again perfectly matches the chemical properties of each functional component.

[0095] In the following tests, TExo@Se / W was from Example 1, TExo@W was from Comparative Example 1, and TExo@Se was from Preparation Example 2.

[0096] II. Evaluation of the anti-inflammatory effect of TExo@Se / W

[0097] RAW 264.7 macrophages were seeded in 6-well plates, and a macrophage inflammation model was established by lipopolysaccharide (LPS) stimulation. Cellular macrophages were then treated with PBS, TExo (from Comparative Example 3), TExo@W, TExo@Se, and TExo@Se / W, respectively. The levels of inflammatory factors were detected by ELISA, and the results are as follows: Figure 3 As shown, compared with the PBS group, all TExo treatment groups were able to reduce the expression of inflammatory factors TNF-α, IL-6 and IL-1β. Among them, the TExo@Se / W treatment group showed the most significant inhibitory effect, indicating that the introduction of Se / W nanocomponents further enhanced the TExo-mediated anti-inflammatory ability.

[0098] III. ROS Removal Efficacy Evaluation of TExo@Se / W

[0099] RAW 264.7 macrophages were seeded in 24-well plates and co-incubated with different concentrations of nanoparticles for 24 h. Then, the plates were treated with 200 nM H2O2 for 3 h, stained with DCFH-DA for 30 min, and samples were collected and analyzed by flow cytometry. Results are as follows: Figure 4 and Figure 5As shown, compared with the PBS group, the intracellular ROS fluorescence intensity of the TExo@Se / W treatment group was significantly reduced, and the ROS level was lower than that of the TExo alone (from Comparative Example 3), TExo@Se and TExo@W treatment groups. This indicates that Se nanoparticles can effectively enhance the antioxidant capacity of the exosome system and achieve the clearance of excess ROS in the inflammatory environment.

[0100] IV. Evaluation of the regulatory effect of TExo@Se / W bacteria on proliferation

[0101] Prepare TExo (from Comparative Example 3), TExo@W, TExo@Se, and TExo@Se / W, adjusting the exosome concentration to 6 mg / mL. Add 100 μL of exosomes to 200 μL of nitrate medium and 1000 CFU of E. coli, incubate at 37°C for 3 hours with aerobic respiration, then fill the culture medium to the top, seal, and incubate for 18 hours with anaerobic respiration. Then, plate and count the exosomes. Figure 6 and Figure 7 As shown, compared with the TExo treatment group, the number of colonies in the TExo@W and TExo@Se / W treatment groups loaded with W element was significantly reduced, indicating that W element can effectively reduce the potential risk of dysbiosis during immunosuppressive therapy.

[0102] V. TExo@Se / W improves symptoms of DSS-induced colitis

[0103] like Figure 8 As shown, a DSS-induced acute colitis mouse model was established, and mice were randomly divided into Healthy, PBS, TExo (from Comparative Example 4), TExo@W, TExo@Se, and TExo@Se / W groups for treatment. During the experiment, mice were continuously administered DSS to induce colonic inflammation, followed by treatment with different materials. After treatment, colonic tissue from each group was collected and its length was measured. Figure 9 and Figure 10 As shown, compared with the Healthy group, the colon of mice in the PBS group after DSS induction was significantly shortened. However, after TExo@Se / W treatment, the colon length of mice was significantly restored, which was better than the TExo, TExo@W and TExo@Se treatment groups alone. This indicates that TExo@Se / W can effectively alleviate DSS-induced colonic injury.

[0104] Further observation of colonic tissue pathological changes was conducted using H&E staining. For example... Figure 11 As shown, mice in the PBS group exhibited significant mucosal structural damage, crypt injury, and inflammatory cell infiltration, while TExo@Se / W treatment resulted in significant restoration of colonic tissue structure, reduced inflammatory infiltration, and a marked decrease in tissue damage. Histological scoring results are shown below. Figure 12 This further demonstrates that TExo@Se / W has a superior therapeutic effect on colitis.

[0105] VI. TExo@Se / W promotes the restoration of intestinal immune homeostasis

[0106] To further investigate the role of TExo@Se / W in regulating the immune microenvironment, flow cytometry was used to detect the proportion of Treg cells in colon tissue. Figure 13 and Figure 14 As shown, compared with the PBS group, the proportion of CD25+Foxp3+Treg cells was significantly increased after TExo@Se / W treatment, and was higher than that of other treatment groups, indicating that TExo@Se / W can effectively promote the recovery of immune tolerance-related cell populations. TExo was derived from control group 4.

[0107] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A Treg exosome selenium-tungsten nanodelivery system, characterized in that, Including Treg-derived exosomes, chitosan, selenium nanoparticles, hexavalent tungsten, and sodium alginate; Chitosan and Treg-derived exosomes combine to form a composite carrier; selenium nanoparticles and hexavalent tungsten are independently co-loaded on the composite carrier, wherein the selenium in the selenium nanoparticles is reduced in situ to form the loaded tungsten in the hexavalent form; Sodium alginate is coated onto the outer layer of a composite carrier loaded with selenium nanoparticles and hexavalent tungsten to form an oral delivery system.

2. The Treg exosome selenium-tungsten nanodelivery system according to claim 1, characterized in that, The molar ratio of selenium to hexavalent tungsten in the selenium nanoparticles is 1:(0.5-2).

3. The Treg exosome selenium-tungsten nanodelivery system according to claim 2, characterized in that, The molar ratio of selenium to hexavalent tungsten in the selenium nanoparticles is 1:

1.

4. The Treg exosome selenium-tungsten nanodelivery system according to claim 1, characterized in that, The mass ratio of chitosan to Treg-derived exosomes is 1:(1-3).

5. The Treg exosome selenium-tungsten nanodelivery system according to claim 1, characterized in that, The Treg-derived exosomes are derived from induced regulatory T cells or natural regulatory T cells.

6. A method for preparing a Treg exosome selenium-tungsten nanodelivery system as described in any one of claims 1-5, characterized in that, Includes the following steps: S1. Preparation of exosome-chitosan composite carrier: Chitosan was dissolved in acetic acid to obtain a chitosan solution, and Treg-derived exosomes were added and mixed. The pH was adjusted to allow the chitosan to bind with the exosomes to form an exosome-chitosan composite carrier. Loading and reduction of S2.Se and W mixed metal ions: Selenite and tungstate were introduced into the composite support system obtained in S1 for coordination loading, and then ascorbic acid was added for in-situ reduction, so that selenite was reduced in-situ to selenium nanoparticles and loaded on the composite support, and tungsten was independently loaded on the composite support in hexavalent form, thus obtaining a composite support loaded with selenium nanoparticles and hexavalent tungsten. S3. Preparation of oral metal nanoparticle delivery system: Sodium alginate solution is mixed with the system obtained in S2 to coat the outer layer of the composite carrier with sodium alginate, thereby obtaining an oral delivery system.

7. The method for preparing the Treg exosome selenium-tungsten nanodelivery system according to claim 6, characterized in that, The concentration of chitosan solution in S1 is 5-10 mg / mL.

8. The method for preparing the Treg exosome selenium-tungsten nanodelivery system according to claim 6, characterized in that, In S2, the selenite is sodium selenite with a concentration of 0.5 mM; the tungstate is sodium tungstate with a concentration of 0.5 mM; and the ascorbic acid has a concentration of 30 mM.

9. The method for preparing the Treg exosome selenium-tungsten nanodelivery system according to claim 6, characterized in that, The in-situ reduction temperature in S2 is 30-40℃, the incubation time for coordination load is 1-3h, and the in-situ reduction incubation time is 1-3h.

10. The use of the Treg exosome selenium-tungsten nanodelivery system according to any one of claims 1-5 in the preparation of a medicament for treating ulcerative colitis.

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