Mucosal epithelial cell-targeted oral ROS-responsive nanozyme and preparation method and application thereof

Abstract

The application discloses a kind of oral ROS response type nano-enzyme targeted to mucosal epithelial cells and its preparation method and application, it is related to biological medicine technical field.The oral ROS response type nano-enzyme includes Ce-CCDs carbon dots and betaine polymer, the betaine polymer is coated on the surface of the Ce-CCDs carbon dots, and forms nanoparticle;The Ce-CCDs carbon dots are prepared by pyrolysis method using cerium source and chlorogenic acid as raw materials.The nano-enzyme prepared by structural innovation and function integration shows outstanding advantages in catalytic activity, targeted delivery, synergistic therapy and industrial application, etc., provides a new technical scheme for efficient and safe treatment of inflammatory bowel disease, and has significant technical innovation and clinical application value.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to an orally administered ROS-responsive nanozyme targeting mucosal epithelial cells, its preparation method, and its application. Background Technology

[0002] Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of autoimmune diseases characterized by chronic, relapsing intestinal inflammation. The course of IBD typically involves continuous progression and periodic relapses, with the long-term chronic inflammatory state significantly reducing patients' quality of life. Although its exact pathogenesis is not fully understood, numerous studies have shown that persistently elevated oxidative stress in the gut microenvironment, disruption of gut microbiota homeostasis, and abnormal activation of the immune system play important roles in the development and progression of IBD.

[0003] Current treatments for IBD rely on 5-aminosalicylic acid derivatives, glucocorticoids, and immunosuppressants. While these can relieve inflammatory symptoms in the short term, their long-term efficacy is limited, and they are accompanied by serious systemic side effects and drug tolerance issues, making a complete cure difficult. Most of these drugs are administered orally, and their convenient administration improves patient compliance, meeting the needs of patients with inflammatory bowel disease who require long-term medication. However, most oral medications have a short residence time in the intestines, requiring multiple doses to achieve therapeutic effects. Furthermore, while oral medications are highly targeted, they are easily absorbed in the upper gastrointestinal tract, leading to 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, reducing drug distribution throughout the body, thereby enhancing efficacy and reducing side effects. However, the highly acidic pH of the stomach, the harsh environment of the gastrointestinal tract with various digestive enzymes, and the multiple barriers within the intestine, including the mucus barrier and the epithelial barrier, pose significant challenges to the colonic targeting ability, retention capacity, and barrier penetration ability of nanoparticles.

[0005] Furthermore, current medications for treating IBD primarily focus on anti-inflammatory and immunomodulatory mechanisms. However, the persistent oxidative stress microenvironment of the gut generates a large number of reactive oxygen species (ROS), which 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 crucial role in clearing excess ROS from inflamed sites. However, in the inflammatory microenvironment of IBD, these natural enzymes are easily inactivated or degraded, resulting in a significant decrease in their antioxidant defense capabilities.

[0006] In recent years, the rise of nanozymes has provided new insights into the treatment of IBD. Nanozymes are a class of nanomaterials that can mimic the catalytic function of natural enzymes, possessing characteristics such as high catalytic efficiency, multiple enzyme activities, excellent physicochemical stability, and good biocompatibility. Compared with natural enzymes, nanozymes exhibit stronger tolerance and designability in complex pathological environments, and can be regulated to achieve multifunctionality through surface modification. Therefore, how to construct a nanozyme system with synergistic activities of multiple enzymes such as SOD, CAT, and GPx to effectively clear ROS at inflammatory sites and regulate immune homeostasis is a challenge 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, this invention aims to develop a novel oral ROS-responsive nanozyme targeting mucosal epithelial cells, thereby providing strong technical support for the treatment of inflammatory bowel disease. Summary of the Invention

[0007] The purpose of this invention is to provide an orally administered ROS-responsive nanozyme targeting mucosal epithelial cells, its preparation method, and its application, thereby addressing the problems existing in the prior art. This orally administered ROS-responsive nanozyme can effectively treat inflammatory bowel disease.

[0008] The structure and surface properties of nanozymes are closely related to their catalytic activity. When designing nanozymes, the electronic structure of catalytic atomic sites can be modulated by modifying the support, ligands, or active site elements, thereby improving electron transfer efficiency and lowering the reaction energy barrier. Chlorogenic acid (CGA) is a natural polyphenol extracted from coffee beans, possessing excellent antioxidant and anti-inflammatory properties due to its abundant phenolic hydroxyl structures. Single-atom carbon dots (Ce-CCDs) can be synthesized by using chlorogenic acid as a carbon source and adding cerium ions for coordination via pyrolysis. As a zero-dimensional nanomaterial, the ultra-small size of carbon dots makes them easier to 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 naturally occurring quaternary ammonium compound found in plant and animal cells. It specifically binds to TBK1 and inhibits its kinase activity, thereby blocking the activation of the downstream IRF3 / NF-κB signaling pathway, inhibiting the expression of pro-inflammatory factors, and exerting an anti-inflammatory effect. On the other hand, betaine can promote the growth of beneficial bacteria (such as Bifidobacteria and Lactobacillus) and inhibit the abundance of pathogenic symbiotic bacteria, thus improving the intestinal microecological environment and regulating the balance of intestinal flora. In addition, betaine polymers such as polysulfobetaine methacrylate (PSB), as zwitterionic polymers, can be used as materials to resist protein contamination. After being modified onto the surface of Ce-CCDs, a hydration layer, or "invisible coating," can be formed. This coating can protect the nanoparticles from passing through the stomach and small intestine to the colon, and can also shield the negative charge of Ce-CCDs, reducing their interaction with intestinal mucins, allowing nanozymes to pass through the mucus barrier smoothly and enhancing cellular uptake.

[0010] Based on this, the present invention provides the following solution:

[0011] This invention provides an orally administered ROS-responsive nanozyme targeting mucosal epithelial cells, comprising Ce-CCD carbon dots and a betaine polymer, wherein the betaine polymer coats the surface of the Ce-CCD carbon dots to form nanoparticles;

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

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

[0014] The present invention also provides a method for preparing the above-mentioned oral ROS-responsive nanozyme, comprising the step of mixing and reacting the Ce-CCDs carbon dots and the betaine polymer to obtain the oral ROS-responsive nanozyme.

[0015] Furthermore, the method for preparing the Ce-CCD carbon dots includes the following steps:

[0016] 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.

[0017] The crude product was subjected to dialysis and drying to obtain the Ce-CCDs carbon dots.

[0018] Furthermore, the pyrolysis reaction is carried out at a temperature of 180°C for 1 hour.

[0019] Furthermore, the mass ratio of the Ce-CCDs carbon dots to the betaine polymer is 2:1.

[0020] The present invention also provides the application of the above-mentioned oral ROS-responsive nanozyme in the preparation of a drug for treating inflammatory bowel disease.

[0021] The present invention also provides a medicament for treating inflammatory bowel disease, the active ingredient of which includes the above-mentioned oral ROS-responsive nanozyme.

[0022] Furthermore, the drug also includes pharmaceutically acceptable excipients.

[0023] Furthermore, the dosage form of the drug is oral liquid, granules, tablets, powder, or pills.

[0024] The present invention discloses the following technical effects:

[0025] This invention utilizes Ce-CCDs carbon dots formed by the pyrolysis of cerium metal and chlorogenic acid as the core, and coats them with betaine polymers to prepare an orally administered ROS-responsive nanozyme targeting mucosal epithelial cells. The Ce-CCDs carbon dots, through the coordination structure of single-atom Ce and O and the p-π conjugated structure of polyphenols, significantly increase the electron density near the Fermi level, resulting in higher electron transfer efficiency and enhanced catalytic effect of the nanozyme, thus exerting a therapeutic effect on enteritis at a relatively low dose. By coating the Ce-CCDs carbon dots with betaine polymers, not only can they remain stable in the gastrointestinal environment and smoothly pass through the stomach and small intestine to the colon, but the effect of intestinal mucin on the nanoparticles is also reduced, allowing the nanoparticles to be smoothly taken up by cells through the colonic mucus layer, achieving highly efficient orally administered targeted therapy. Betaine itself has anti-inflammatory effects and can also regulate the balance of intestinal flora and improve the intestinal flora that has been damaged by inflammation. The betaine polymer coating-coated carbon dot nanoenzyme not only integrates the advantages of nanomaterial delivery, but also works synergistically to treat inflammatory bowel disease.

[0026] The nanozyme preparation process provided by this invention features simple operation, mild reaction conditions, and high preparation efficiency, facilitating large-scale production. Furthermore, the raw materials used are from stable sources with good biocompatibility, meeting the industrialization requirements of pharmaceutical preparations. Its oral administration method aligns with clinical medication habits, resulting in high patient compliance. It overcomes the inconvenience of using some injectable anti-inflammatory agents and possesses broad prospects for clinical translation and market application.

[0027] Through structural innovation and functional integration, this invention enables the prepared nanozymes to exhibit outstanding advantages in catalytic activity, targeted delivery, synergistic therapy, and industrial application, providing a new technical solution for the efficient and safe treatment of inflammatory bowel disease, and possessing significant technological innovation and clinical application value. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0029] Figure 1 A schematic diagram illustrating the construction and mechanism of action of orally administered ROS-responsive nanozymes;

[0030] Figure 2 Zeta potential plots for Ce-CCDs and Ce-CCDs@PSB;

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

[0032] Figure 4 The graphs show the particle size and zeta potential changes of Ce-CCDs@PSB in simulated gastric juice (SGF), simulated small intestinal juice (SIF), and simulated colonic juice (SCF). Specifically, A represents the particle size variation of Ce-CCDs@PSB in SGF; B represents the zeta potential variation of Ce-CCDs@PSB in SGF; C represents the particle size variation of Ce-CCDs@PSB in SIF; D represents the zeta potential variation of Ce-CCDs@PSB in SIF; E represents the particle size variation of Ce-CCDs@PSB in SCF; and F represents the zeta potential variation of Ce-CCDs@PSB in SCF.

[0033] Figure 5 A comparison of the diffusion coefficients of Ce-CCDs and Ce-CCDs@PSB in mucin solution;

[0034] Figure 6 A statistical graph of SOD activity of Ce-CCDs@PSB;

[0035] Figure 7 A statistical graph of CAT activity of Ce-CCDs@PSB;

[0036] Figure 8 A statistical graph of GPx activity of Ce-CCDs@PSB;

[0037] Figure 9 The graph shows the results of NCM-460 proliferation after treatment with different concentrations of Ce-CCDs@PSB.

[0038] Figure 10 The image shows the results of detecting the proliferation of RAW264.7 cells after treatment with different concentrations of Ce-CCDs@PSB.

[0039] Figure 11 The image shows the cell viability of NCM-460 cells after 6 hours of co-incubation with different concentrations of Ce-CCDs@PSB in hydrogen peroxide.

[0040] Figure 12 The image shows the cell viability of RAW264.7 cells after 6 hours of co-incubation in hydrogen peroxide with different concentrations of Ce-CCDs@PSB.

[0041] Figure 13 This is a graph showing the changes in body weight of mice during the experiment.

[0042] Figure 14 This is a graph showing the changes in the disease activity index during the mouse experiment;

[0043] Figure 15 A statistical graph showing the colon length of mice that received different treatments on day 15. Detailed Implementation

[0044] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0045] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0046] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0047] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This specification and embodiments are merely exemplary.

[0048] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0049] like Figure 1 As shown, the oral nanoenzyme system of the present invention uses Ce-CCDs carbon dots formed by the pyrolysis of cerium metal and chlorogenic acid as the core. Then, after synthesizing polysulfobetaine from betaine, it is coated on the surface of Ce-CCDs carbon dots to form Ce-CCDs@PSB.

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

[0051] (1) Preparation of Ce-CCDs

[0052] 0.25 g of chlorogenic acid and 0.2 g of cerium nitrate hexahydrate were added sequentially to 10 mL of formamide solution and stirred magnetically until completely dissolved. The mixture was then transferred to a round-bottom flask and reacted in an oil bath at 180 °C for 1 h. The crude product was cooled to room temperature and placed in a dialysis bag (MwCO: 3500 Da) for dialysis for 7 days. The retained sample in the dialysis bag was centrifuged at 9000 rpm for 15 min, and the supernatant was filtered through 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 dissolved in 4 mL of deionized water, and 0.34 mL of acrylic acid was added. The mixture was continuously stirred magnetically to form a transparent monomer mixture. 1.08 mL of 2 wt% potassium persulfate solution was added to the monomer solution, followed by 0.03 mL of tetramethylethylenediamine. The mixture was stirred for 10 min to ensure homogeneity. The mixture 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 resulting polymer solution was placed in a dialysis bag (MwCO: 3500 Da) and dialyzed for 5 days to obtain the retentate, which is the purified polymer solution. The purified polymer solution was freeze-dried to obtain PSB.

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

[0056] First, prepare a 2 mg / mL Ce-CCDs aqueous solution. Add 1 mL of the 2 mg / mL Ce-CCDs aqueous solution to a beaker, then slowly add 1 mL of 1 mg / mL PSB solution dropwise. After magnetic stirring for 6 h, place the resulting solution into a dialysis bag (MwCO: 7000 Da) and dialyze for 7 days to obtain the retentate, which is the purified nanoparticle solution. Freeze-dry the purified nanoparticle solution to obtain Ce-CCDs@PSB.

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

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

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

[0060] The zeta potentials of Ce-CCDs and Ce-CCDs@PSB were measured using a dynamic light scattering particle size analyzer. The results are shown in [Figure number missing]. Figure 2 The results showed that the zeta potential of Ce-CCDs was around -21 mV, while the zeta potential of Ce-CCDs@PSB was close to neutral. This electroneutrality endows them with the ability to penetrate the intestinal mucus barrier and be taken up by cells.

[0061] 2. Morphological observation of nanoparticles

[0062] Ce-CCDs@PSB were subjected to high-resolution imaging using transmission electron microscopy (TEM) to observe their morphology and particle size. The results are shown in [Figure number missing]. Figure 3 The results showed that Ce-CCDs@PSB exhibited good dispersibility and spherical morphology, with a particle size of approximately 3 nm.

[0063] 3. Stability evaluation of nanoparticles in the gastrointestinal environment

[0064] Ce-CCDs@PSB were incubated for 72 h in simulated gastric juice (SGF), simulated small intestinal juice (SIF), and simulated colonic juice (SCF), respectively, and their particle size and zeta potential changes were measured. The results are shown in [Figure number missing]. Figure 4 .

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

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

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

[0068] Depend on Figure 5 It can be seen that Ce-CCDs@PSB exhibits superior diffusion efficiency in viscous environments, with its diffusion coefficient significantly improved compared to Ce-CCDs.

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

[0070] This invention evaluated the multi-enzyme activities (SOD, CAT, GPx) of the synthesized Ce-CCDs@PSB. SOD and GPx activities were determined using a kit. CAT activity was measured by adding hydrogen peroxide (3 wt.%, 1 mL) to a PBS buffer solution (pH 7.4, 10 mL) containing nanozymes (1 mg / mL, 225 µL), and monitoring the dissolved oxygen concentration in real time using a dissolved oxygen meter. Measurement data were recorded at 5-second intervals within a 3-minute reaction cycle. Results are shown below. Figures 6-8 .

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

[0072] Example 3: Biosafety evaluation of Ce-CCDs@PSB

[0073] The in vitro biosafety of Ce-CCDs@PSB nanoparticles was evaluated using the Cell Counting Kit-8 (CCK-8) assay after co-incubating with colonic epithelial cells (NCM-460) and mouse mononuclear macrophage leukemia cells (RAW264.7) for 24 hours. Results are shown in the table below. Figures 9-10 .

[0074] Depend on Figures 9-10 It was found that within the concentration range of ≤250 µg / mL, Ce-CCDs@PSB had no significant effect on the viability of colonic epithelial cells and macrophages, demonstrating 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 cells were placed under oxidative stress (0.5 mM hydrogen peroxide) and co-incubated with Ce-CCDs@PSB to simulate the oxidative stress environment in inflammatory pathology. The protective effect of the nanoparticles on cells was evaluated using the CCK-8 cell viability assay. The results are shown below. Figures 11-12 .

[0077] Depend on Figures 11-12 It can be seen that, 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 a good cell protection effect.

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

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

[0080] This invention uses 5-aminosalicylic acid (5-ASA), commonly used in the clinical treatment of IBD, as a positive control. C57BL / 6 mice were randomly divided into five groups (n=5 per group): one group served as a blank control (i.e., normal mice), and four groups served as ulcerative colitis model groups. Mice underwent acclimatization one week prior to the experiment. Mice in the ulcerative colitis model groups were given 3% DSS solution instead of drinking water from day 0 to day 6 to induce colitis. Subsequently, 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, respectively. The mice were euthanized on day 15. Throughout the 15-day experiment, body weight, fecal morphology, and fecal bleeding were assessed every two days. After euthanasia, the mice were dissected to measure colon length. Experimental results are shown below. Figures 13-15 .

[0081] like Figure 13 As shown, throughout the experiment, mice in the PBS group experienced weight loss after drinking 3% DSS solution, indicating the successful establishment of the ulcerative colitis model. Compared with the PBS group, mice in the Ce-CCDs@PSB treatment group showed more significant weight recovery, exceeding the recovery level of the 5-ASA positive drug group, indicating that Ce-CCDs@PSB can effectively alleviate DSS-induced weight loss and has a good therapeutic effect.

[0082] like 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 superior to that of the Ce-CCDs and 5-ASA treatment groups. This indicates that Ce-CCDs@PSB can effectively improve colitis-related clinical symptoms and reduce intestinal inflammatory response.

[0083] DSS-induced colitis is often accompanied by colonic shortening. For example... Figure 15 As shown, the colon length of mice in the Ce-CCDs@PSB treatment group was significantly longer than that in the PBS group and the Ce-CCDs group, and close to that in 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 structural integrity of the colon.

[0084] In summary, Ce-CCDs@PSB demonstrated significant therapeutic effects in a DSS-induced mouse model of ulcerative colitis, effectively alleviating weight loss, improving disease activity index, and preventing colonic shortening, with efficacy comparable to that of the clinically commonly used drug 5-ASA. These results fully demonstrate the potential of Ce-CCDs@PSB as a novel nanomedicine for the treatment of inflammatory bowel disease.

[0085] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. An oral ROS-responsive nanozyme for treating inflammatory bowel disease, 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. The betaine polymer is polysulfobetaine methacrylate; The mass ratio of the Ce-CCDs carbon dots to the betaine polymer is 2:

1.

2. A method of preparing the oral ROS-responsive nanoscale enzyme according to claim 1, characterized by, The method includes the step of mixing and reacting the Ce-CCDs carbon dots and the betaine polymer to obtain the oral ROS-responsive nanozyme.

3. The production method according to claim 2, characterized by, 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.

4. The production method according to claim 3, characterized by, The pyrolysis reaction was carried out at a temperature of 180°C for 1 hour.

5. The use of the oral ROS-responsive nanozyme as described in claim 1 in the preparation of a medicament for treating inflammatory bowel disease.

6. A medicament for treating inflammatory bowel disease, characterized by comprising a compound of the formula (I) or a pharmaceutically acceptable salt thereof. The active ingredient includes the oral ROS-responsive nanozyme as described in claim 1.

7. The medicament according to claim 6, characterized in that, The drug also includes pharmaceutically acceptable excipients.

8. The medicament according to claim 7, characterized in that, The dosage form of the drug is oral liquid, granules, tablets, powder, or pills.

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