Mucosal epithelial cell targeted oral ROS responsive nano-enzyme as well as preparation method and application of mucosal epithelial cell targeted oral ROS responsive nano-enzyme

Abstract

The invention discloses a mucosal epithelial cell targeted oral ROS response type nano-enzyme as well as a preparation method and application thereof, and relates to the technical field of biological medicines. The oral ROS response type nano-enzyme comprises Ce-CDs carbon dots and a betaine polymer, and the betaine polymer is coated on the surfaces of the Ce-CDs carbon dots to form nano-particles; the Ce-CCDs carbon dots are prepared by taking a metal cerium source and chlorogenic acid as raw materials through a pyrolysis method. Through structural innovation and function integration, the prepared nano-enzyme shows outstanding advantages in the aspects of catalytic activity, targeted delivery, collaborative treatment, industrial application and the like, a new technical scheme is provided for efficient and safe treatment of inflammatory bowel diseases, and the nano-enzyme has remarkable technical innovation and clinical application value.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, in particular to a mucosal epithelial cell targeted oral ROS-responsive nano-enzyme and a preparation method and application thereof. BACKGROUND

[0002] Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease is a kind of autoimmune disease characterized by chronic and recurrent intestinal inflammation. The course of IBD usually shows continuous progression and periodic recurrence, and the long-term chronic inflammatory state significantly reduces the quality of life of patients. Although the exact pathogenesis has not been fully elucidated, a large number of studies have shown that the continuous increase of oxidative stress in the intestinal microenvironment, the destruction of the flora homeostasis and the abnormal activation of the immune system play an important role in the occurrence and development of IBD.

[0003] Current treatment options for IBD rely on 5-aminosalicylic acid drugs, glucocorticoid drugs and immunosuppressants, etc. Although they can alleviate inflammatory symptoms in the short term, the long-term efficacy is limited, and is accompanied by serious systemic side effects and drug resistance problems, making it difficult to cure. Most of these drugs are administered orally, and their simple administration can improve patient compliance and meet the needs of patients with inflammatory bowel disease who need long-term medication. However, most oral drugs stay in the intestinal tract for a short time and need to be administered multiple times to achieve therapeutic effects. In addition, oral drugs are effective in targeting and are easily absorbed in the upper digestive tract, causing systemic toxicity.

[0004] Oral drug delivery systems based on nanotechnology have shown great potential in the treatment of IBD. Oral nanoparticles can achieve efficient drug delivery and sustained release, reduce drug distribution in the whole body, and thus enhance efficacy and reduce side effects. However, the harsh environment of the stomach with strong acidity and various digestive enzymes in the gastrointestinal tract, as well as the multiple barriers in the intestinal tract including the mucus barrier and epithelial barrier, pose great challenges to the colon targeting ability, retention ability and barrier penetration ability of nanoparticles.

[0005] In addition, the mechanism of action of current drugs for treating IBD mainly focuses on anti-inflammatory and immune regulation. However, the sustained oxidative stress microenvironment in the intestine can produce a large number of active oxygen free radicals, which will continuously activate immune cells to produce pro-inflammatory cytokines, hindering the treatment of inflammatory bowel disease. Under physiological conditions, the redox balance in cells is maintained by a series of enzymes, among which antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) play a key role in clearing excess active oxygen at the inflammation site. However, in the inflammatory microenvironment of IBD, these natural enzymes are easily inactivated or degraded, and their antioxidant defense capacity is significantly reduced.

[0006] In recent years, the rise of nanozymes has provided new ideas for the treatment of IBD. Nanozymes are a class of nanomaterials that can mimic the catalytic function of natural enzymes, with high catalytic efficiency, multiple enzyme activity, excellent physical and chemical stability, and good biocompatibility. Compared with natural enzymes, nanozymes show stronger tolerance and designability in complex pathological environments, and can be multifunctionally regulated through surface modification. Therefore, how to construct a nanozyme system with multiple enzyme synergistic activities such as SOD, CAT, GPx, etc. to effectively scavenge ROS at the inflammatory site and regulate immune homeostasis is a difficult point in the field of IBD treatment. In addition, existing nanoparticles also have limitations in responding to changes in the intestinal microenvironment and regulating the balance of intestinal flora. Based on this, the present invention aims to develop a novel mucosal epithelial cell-targeted oral ROS-responsive nanozyme, thereby providing strong technical support for the treatment of inflammatory bowel disease. SUMMARY

[0007] The purpose of the present invention is to provide a mucosal epithelial cell-targeted oral ROS-responsive nanozyme and its preparation method and application, in order to solve the problems existing in the prior art. The oral ROS-responsive nanozyme can effectively treat inflammatory bowel disease.

[0008] The structure and surface properties of nanozymes are closely related to catalytic activity. In the design of nanozymes, the electronic structure of the catalytic atom site can be regulated by modifying the carrier, ligand or active site element, which can improve the electron transfer efficiency and reduce the reaction energy barrier. Chlorogenic acid (CGA) is a natural polyphenol extracted from coffee beans, which has excellent antioxidant and anti-inflammatory properties due to its rich phenolic hydroxyl structure. By using chlorogenic acid as a carbon source and adding cerium ions for coordination, single-atom carbon dots (Ce-CCDs) can be synthesized. Carbon dots are a kind of zero-dimensional nanomaterials, and their ultra-small size makes them more easily penetrate the intestinal mucus layer and be taken up by cells. The unique p-π conjugated structure of polyphenols can form a Ce-O coordination environment, thereby enhancing the electron density near the Fermi level of Ce-CCDs, resulting in higher catalytic activity.

[0009] Betaine is a quaternary amine compound that exists naturally in animal and plant cells. It can specifically bind to TBK1 and inhibit its kinase activity, thereby blocking the activation of downstream IRF3 / NF-κB signaling pathways and inhibiting the expression of pro-inflammatory factors, thus playing an anti-inflammatory role. On the other hand, betaine can promote the growth of beneficial bacteria (such as bifidobacteria and lactic acid bacteria) and inhibit the abundance of pathogenic symbiotic bacteria, thereby improving the intestinal microecological environment and regulating the balance of intestinal flora. In addition, betaine polymers such as polysulfobetaine methacrylate (PSB) can be used as a material for anti-protein contamination. When modified on the surface of Ce-CCDs, it can form a hydration layer, i.e. a "stealth coating", which can not only protect the nanoparticles from passing through the stomach and small intestine to reach the colon, but also shield the negative charge of Ce-CCDs, reducing their interaction with intestinal mucin, allowing the nanoscale enzyme to pass through the mucus barrier and enhance cell uptake.

[0010] Based on this, the present application provides the following scheme:

[0011] The present application provides a mucosal epithelial cell targeted oral ROS responsive nanoscale enzyme, comprising Ce-CCDs carbon dots and betaine polymers, the betaine polymers are coated on the surface of the Ce-CCDs carbon dots to form nanoparticles.

[0012] The Ce-CCDs carbon dots are prepared by pyrolysis method using cerium metal source and chlorogenic acid as raw materials.

[0013] Further, the betaine polymer is polysulfobetaine methacrylate.

[0014] The present application also provides a preparation method of the above-mentioned oral ROS responsive nanoscale enzyme, comprising the steps of mixing and reacting the Ce-CCDs carbon dots and the betaine polymers to obtain the oral ROS responsive nanoscale enzyme.

[0015] Further, the preparation method of the Ce-CCDs carbon dots comprises the following steps:

[0016] Dissolve chlorogenic acid and cerium nitrate hexahydrate in a solvent to obtain a mixed solution, and then perform pyrolysis reaction to obtain a crude product;

[0017] Dialysis treatment and drying treatment are performed on the crude product to obtain the Ce-CCDs carbon dots.

[0018] Further, the temperature of the pyrolysis reaction is 180℃, and the time is 1h.

[0019] Further, the mass ratio of the Ce-CCDs carbon dots and the betaine polymers is 2:1.

[0020] The application also provides application of the oral ROS-responsive nanoscale enzyme in the preparation of a drug for treating inflammatory bowel disease.

[0021] The application also provides a drug for treating inflammatory bowel disease, wherein the active ingredient comprises the oral ROS-responsive nanoscale enzyme.

[0022] Further, the drug further comprises a pharmaceutically acceptable excipient.

[0023] Further, the drug is in the form of an oral liquid, granules, tablets, powder or pills.

[0024] The application discloses the following technical effects:

[0025] The application adopts Ce-CCDs carbon dots formed by pyrolysis of cerium and chlorogenic acid as a core, and a betaine polymer is coated to prepare an oral ROS-responsive nanoscale enzyme targeting mucosal epithelial cells. The single-atom Ce and O coordination structure and the p-π conjugated structure of the polyphenol of the Ce-CCDs carbon dots significantly increase the electron density near the Fermi level, so that the electron transfer efficiency is higher, and the catalytic effect of the nanoscale enzyme is enhanced, thereby playing a therapeutic role on intestinal inflammation at a smaller dose. The betaine polymer is coated on the surface of the Ce-CCDs carbon dots, so that the nanoscale enzyme can maintain stability in the gastrointestinal environment, smoothly pass through the stomach and small intestine to reach the colon, reduce the effect of intestinal mucin on the nanoscale particles, and enable the nanoscale particles to be smoothly taken up by cells through the colon mucus layer, so that oral high-efficiency targeted treatment is achieved. The betaine itself has an anti-inflammatory effect, and can also regulate the balance of intestinal flora, improve the intestinal flora damaged by inflammation, and the carbon dot nanoscale enzyme coated with the betaine polymer coating not only integrates the advantages of nanomaterial delivery, but also synergistically plays a role in treating inflammatory bowel disease.

[0026] The nanoscale enzyme preparation process provided by the application has the characteristics of simple operation, mild reaction conditions and high preparation efficiency, is convenient for scale production, and the raw materials used are stable in source and good in biocompatibility, meeting the industrialization requirements of pharmaceutical preparations. The oral administration mode is consistent with the clinical medication habit, and the patient compliance is high, which overcomes the inconvenience of using some injection anti-inflammatory preparations, and has a wide clinical transformation and market application prospect.

[0027] The application realizes structural innovation and functional integration, so that the prepared nanoscale enzyme exhibits outstanding advantages in catalytic activity, targeted delivery, synergistic treatment and industrial application, and provides a new technical scheme for efficient and safe treatment of inflammatory bowel disease, and has significant technical innovation and clinical application value. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to make the technical solutions in the embodiments of the present application or the prior art clearer, the accompanying drawings needed in the embodiments will be briefly introduced below. Obviously, the accompanying drawings in the following description only constitute some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained from these drawings without creative effort.

[0029] Figure 1 Schematic diagram of construction and action principle of ROS-responsive nanoscale enzyme for oral administration;

[0030] Figure 2 Zeta potential diagram of Ce-CCDs and Ce-CCDs@PSB;

[0031] Figure 3 TEM diagram of Ce-CCDs@PSB;

[0032] Figure 4 Particle size and Zeta potential change diagram of Ce-CCDs@PSB in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colon fluid (SCF); wherein, A is the particle size change diagram of Ce-CCDs@PSB in SGF; B is the Zeta potential change diagram of Ce-CCDs@PSB in SGF; C is the particle size change diagram of Ce-CCDs@PSB in SIF; D is the Zeta potential change diagram of Ce-CCDs@PSB in SIF; E is the particle size change diagram of Ce-CCDs@PSB in SCF; F is the Zeta potential change diagram of Ce-CCDs@PSB in SCF;

[0033] Figure 5 Comparison diagram of diffusion coefficients of Ce-CCDs and Ce-CCDs@PSB in mucin solution;

[0034] Figure 6 Statistical diagram of SOD activity of Ce-CCDs@PSB;

[0035] Figure 7 Statistical diagram of CAT activity of Ce-CCDs@PSB;

[0036] Figure 8 Statistical diagram of GPx activity of Ce-CCDs@PSB;

[0037] Figure 9 Detection result diagram of proliferation of NCM-460 after treatment with Ce-CCDs@PSB of different concentrations;

[0038] Figure 10 Detection result diagram of proliferation of RAW264.7 after treatment with Ce-CCDs@PSB of different concentrations;

[0039] Figure 11 Figure for the cell viability of NCM-460 after 6 hours of incubation in hydrogen peroxide with different concentrations of Ce-CCDs@PSB;

[0040] Figure 12 Figure for the cell viability of RAW264.7 after 6 hours of incubation in hydrogen peroxide with different concentrations of Ce-CCDs@PSB;

[0041] Figure 13 Figure for the body weight change during the mouse experiment;

[0042] Figure 14 Figure for the disease activity index change during the mouse experiment;

[0043] Figure 15 Figure for the colon length of mice receiving different treatments on day 15. DETAILED DESCRIPTION

[0044] Various example embodiments of the present application will now be described in detail with reference to the drawings. The detailed description is made with reference to the drawings, in which like reference numerals represent like elements throughout the several views. The following embodiments are examples of how the application can be implemented. The following embodiments are not intended to limit the scope of the application.

[0045] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. In addition, where particular ranges of values are given, understand that each intervening value, to the upper or lower limit of the ranges is also specifically included. The upper and lower limits of these intervening values are also specifically included within the scope of the present application. These smaller ranges are not necessarily independently specific embodiments, unless otherwise indicated. Each smaller range that falls within the broader ranges expressly indicated in this application are specifically included in the present application.

[0046] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, the preferred methods and materials are described. All patents, patent applications, publications, and descriptions mentioned herein are incorporated by reference to disclose and describe the methods and / or materials in connection with which the patents, patent applications, publications, and descriptions are cited.

[0047] Many modifications and variations of this application can be made in the light of the above teachings without departing from the spirit and scope thereof, and it is to be understood that all such modifications and variations warrant the patentable subject matter under the patent laws. Other embodiments of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application disclosed herein. For example, the specification can be used as a textbook for preparing like compositions, devices, and methods. The specification and examples give guidance for the selection and preparation of materials useful in the application. The application is only as limited by the claims.

[0048] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” and the like are open-ended terms that are intended to be synonymous with each other, i.e., to include, but not limited to.

[0049] As shown in Figure 1 The present application is a novel oral nanoscale enzyme system. The system is prepared by synthesizing a Ce-CCDs carbon dot using cerium and chlorogenic acid as the core, and then coating the carbon dot with a polysulfobetaine synthesized from betaine.

[0050] Example 1 Preparation of Ce-CCDs@PSB

[0051] (1) Preparation of Ce-CCDs

[0052] In a 10 mL formamide solution, 0.25 g of chlorogenic acid and 0.2 g of cerium nitrate hexahydrate were added in sequence, and continuous magnetic stirring was performed to completely dissolve them. The mixed solution was transferred to a round-bottom flask, which was placed in an oil bath at 180 °C for 1 h. After cooling at room temperature, the crude product was placed in a dialysis bag (MwCO: 3500 Da) and dialyzed for 7 days. The sample retained in the dialysis bag was centrifuged at 9000 rpm for 15 min, and the supernatant was filtered using a 0.22 µm filter membrane. The filtrate was freeze-dried to obtain Ce-CCDs.

[0053] (2) Synthesis of polysulfobetaine methacrylate (PSB)

[0054] 1.392 g of sulfobetaine methacrylate was weighed into 4 mL of deionized water, and 0.34 mL of acrylic acid was added. Continuous magnetic stirring was performed to form a transparent monomer mixture solution. To the above monomer solution, 1.08 mL of 2 wt% potassium persulfate solution was added, followed by the addition of 0.03 mL of tetramethyl ethylenediamine. After stirring for 10 min, the system was mixed uniformly. The mixed solution was transferred to a round-bottom flask and reacted at 60 °C for 12 h. The pH of the solution was adjusted to 7.4 using sodium hydroxide solution. The obtained polymer solution was placed in a dialysis bag (MwCO: 3500 Da) and dialyzed for 5 days to obtain the retentate, i.e., the purified polymer solution. The purified polymer solution was freeze-dried to obtain PSB.

[0055] (3) Preparation of Ce-CCDs@PSB

[0056] Firstly, 2 mg / mL Ce-CCDs aqueous solution was prepared. 1 mL of 2 mg / mL Ce-CCDs aqueous solution was taken into a beaker, then 1 mL of 1 mg / mL PSB solution was added dropwise slowly, and the resulting solution was placed in a dialysis bag (MwCO: 7000 Da) after magnetic stirring for 6 h. The dialysis was carried out for 7 days to obtain the retentate, i.e. the purified nanoparticle solution. The purified nanoparticle solution was freeze-dried to obtain Ce-CCDs@PSB.

[0057] Example 2 Characterization of Ce-CCDs@PSB

[0058] The Ce-CCDs@PSB prepared in Example 1 was characterized as follows:

[0059] 1. Measurement of the hydrated particle size and potential of the nanoparticles

[0060] The Zeta potential of Ce-CCDs and Ce-CCDs@PSB was detected by dynamic light scattering particle size analyzer, and the results are shown in Figure 2 . The results show that the Zeta potential of Ce-CCDs is about -21 mV, while the Zeta potential of Ce-CCDs@PSB is close to neutral. The electrically neutral characteristic can endow it with the ability to penetrate the intestinal mucus barrier and be taken up by cells.

[0061] 2. Observation of the morphology of the nanoparticles

[0062] Ce-CCDs@PSB was imaged by transmission electron microscopy (TEM) to observe its morphology and particle size, and the results are shown in Figure 3 . The results show that Ce-CCDs@PSB has good dispersibility and spherical morphology, and the particle size is about 3 nm.

[0063] 3. Evaluation of the stability of the nanoparticles in the gastrointestinal environment

[0064] Ce-CCDs@PSB was incubated in simulated gastric fluid (SGF), simulated small intestinal fluid (SIF) and simulated colonic fluid (SCF) for 72 h, and the changes in particle size and Zeta potential were measured, and the results are shown in Figure 4 .

[0065] As can be seen from Figure 4 : Ce-CCDs@PSB can remain stable for a long time in the simulated gastrointestinal fluid environment, indicating that it meets the requirements for oral administration.

[0066] 4. Evaluation of the ability of the nanoparticles to penetrate the mucus layer

[0067] Ce-CCDs and Ce-CCDs@PSB labeled with fluorescence were mixed with 15 mg / mL mucin solution used to simulate the intestinal mucus layer, and the diffusion behavior of each nanoparticle in the solution was analyzed by tracking the Brownian motion trajectory of the nanoparticles using a nanoparticle tracking analyzer, and the diffusion coefficient was calculated. The results are shown in Figure 5 .

[0068] It can be seen from Figure 5 that Ce-CCDs@PSB exhibits more excellent diffusion efficiency in the mucus environment, and its diffusion coefficient is significantly improved compared with Ce-CCDs.

[0069] 5. Evaluation of the pseudo-enzyme activity of the nanoparticles

[0070] The present application evaluates the multi-enzyme activities of the synthesized Ce-CCDs@PSB, such as SOD, CAT, and GPx, wherein the SOD and GPx activities are determined by a kit, and the CAT activity is determined by adding hydrogen peroxide (3 wt.%, 1 mL) into a PBS buffer solution (pH 7.4, 10 mL) containing nanoscale enzymes (1 mg / mL, 225 µL), and real-time monitoring of the dissolved oxygen concentration is performed using a dissolved oxygen detector, and the measurement data is recorded at intervals of 5 seconds within a 3-minute reaction period. The results are shown in Figures 6-8 .

[0071] It can be seen from Figure 6 , Figure 7 and Figure 8 that within a certain range, as the concentration of Ce-CCDs@PSB increases, the catalytic activity increases, and a high catalytic activity can be achieved at a relatively low concentration.

[0072] Example 3: Evaluation of the biological safety of Ce-CCDs@PSB

[0073] By incubating Ce-CCDs@PSB with colon epithelial cells (NCM-460) and mouse monocyte macrophage leukemia cells (RAW264.7) for 24 hours, the in vitro biological safety of the nanoparticles was evaluated using a cell counting kit-8 (CCK-8) cell viability assay, and the results are shown in Figures 9-10 .

[0074] It can be seen from Figures 9-10 that within a concentration range of ≤250 µg / mL, Ce-CCDs@PSB has no significant effect on the viability of colon epithelial cells and macrophages, proving that the material has good biocompatibility.

[0075] Example 4: Evaluation of the protective effect of Ce-CCDs@PSB on cells

[0076] To evaluate the cytoprotective effect of Ce-CCDs@PSB nanoparticles, NCM-460 cells and RAW264.7 were placed under oxidative stress (0.5 mM hydrogen peroxide) and Ce-CCDs@PSB was added for co-incubation, simulating the oxidative stress environment in inflammatory pathology. The cytoprotective effect of nanoparticles on cells was evaluated by CCK-8 cell viability assay. The detection results are shown in Figures 11-12 .

[0077] As can be seen from Figures 11-12 , compared with the control group, the cell viability of the Ce-CCDs@PSB nanoparticle treatment group was significantly improved, indicating that Ce-CCDs@PSB has good cytoprotective effect.

[0078] Example 5 Evaluation of the therapeutic effect of Ce-CCDs@PSB on inflammatory bowel disease

[0079] The present application evaluates the therapeutic effect of Ce-CCDs@PSB in a DSS-induced ulcerative colitis model.

[0080] The present application uses 5-aminosalicylic acid (5-ASA), which is commonly used in the clinical treatment of IBD, as a positive drug. C57BL / 6 mice were selected for the experiment and randomly divided into five groups (5 mice per group), one of which was a blank control group (i.e. normal mice), and the other four groups were ulcerative colitis model groups. The mice completed adaptive feeding one week before the experiment. The ulcerative colitis model mice drank 3% DSS solution instead of drinking water from day 0 to day 6 to induce colitis. Subsequently, the mice received oral administration of PBS, 30 mg / kg 5-ASA, 30 mg / kg Ce-CCDs, or 30 mg / kg Ce-CCDs@PSB on days 7, 9, 11, and 13 of the experiment, and the experimental mice were euthanized on day 15. Body weight, stool form, and fecal bleeding were assessed every two days during the entire 15-day experiment. After euthanasia of the mice, the colon length was measured. The experimental results are shown in Figures 13-15 .

[0081] As shown in Figure 13 , the PBS group of mice showed weight loss after drinking 3% DSS solution, indicating that the ulcerative colitis model was successfully established. Compared with the PBS group, the body weight of the Ce-CCDs@PSB treatment group of mice recovered more significantly, exceeding the recovery level of the 5-ASA positive drug group, indicating that Ce-CCDs@PSB can effectively alleviate the weight loss caused by DSS and has good therapeutic effect.

[0082] As shown in Figure 14As shown, the disease activity index of the Ce-CCDs@PSB treatment group was significantly lower than that of the PBS group, and the effect was better than that of the Ce-CCDs and 5-ASA treatment groups. This indicates that Ce-CCDs@PSB can effectively improve the clinical symptoms related to colitis and reduce intestinal inflammatory response.

[0083] DSS-induced colitis is usually accompanied by colon shortening. As shown in FIG. 6, the colon length of the Ce-CCDs@PSB treatment group was significantly longer than that of the PBS group and the Ce-CCDs group, and was close to that of the blank control group and the 5-ASA treatment group. This indicates that Ce-CCDs@PSB can effectively inhibit tissue shortening caused by colonic inflammation and protect the integrity of the colon structure. Figure 15

[0084] In summary, Ce-CCDs@PSB showed significant therapeutic effect in the DSS-induced mouse ulcerative colitis model, effectively alleviated weight loss, improved disease activity index, and prevented colon shortening, and its efficacy was comparable to that of the clinically commonly used drug 5-ASA. These results fully demonstrate the potential of Ce-CCDs@PSB as a new type of nanodrug for the treatment of inflammatory bowel disease.

[0085] The above-described embodiments are merely preferred modes of the present application and are not intended to limit the scope of the present application. Various modifications and improvements to the technical solutions of the present application made by those of ordinary skill in the art without departing from the design spirit of the present application shall fall within the scope of protection of the present application as defined by the claims.​

Claims

1. An orally administered ROS-responsive nanozyme targeting mucosal epithelial cells, characterized in that, It includes Ce-CCDs carbon dots and betaine polymer, wherein the betaine polymer coats the surface of the Ce-CCDs carbon dots to form nanoparticles; The Ce-CCDs carbon dots are prepared by pyrolysis using cerium metal source and chlorogenic acid as raw materials.

2. The oral ROS-responsive nanozyme according to claim 1, characterized in that, The betaine polymer is polysulfobetaine methacrylate.

3. A method for preparing an orally administered ROS-responsive nanozyme as described in any one of claims 1-2, characterized in that, The preparation method includes the following steps: The Ce-CCDs carbon dots and the betaine polymer are mixed and reacted to obtain the oral ROS-responsive nanozyme.

4. The preparation method according to claim 3, characterized in that, The method for preparing the Ce-CCD carbon dots includes the following steps: Chlorogenic acid and cerium nitrate hexahydrate were dissolved in a solvent to obtain a mixed solution, which was then subjected to a pyrolysis reaction to obtain the crude product. The crude product was subjected to dialysis and drying to obtain the Ce-CCDs carbon dots.

5. The preparation method according to claim 4, characterized in that, The pyrolysis reaction was carried out at a temperature of 180°C for 1 hour.

6. The preparation method according to claim 3, characterized in that, The mass ratio of the Ce-CCDs carbon dots to the betaine polymer is 2:

1.

7. The use of an orally administered ROS-responsive nanozyme as described in claim 1 or 2 in the preparation of a medicament for treating inflammatory bowel disease.

8. A drug for treating inflammatory bowel disease, characterized in that, The active ingredient includes the oral ROS-responsive nanozyme as described in claim 1 or 2.

9. The medicament according to claim 8, characterized in that, The drug also includes pharmaceutically acceptable excipients.

10. The medicament according to claim 8, characterized in that, The dosage form of the drug is oral liquid, granules, tablets, powder, or pills.

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