Nanoparticle for delivering nucleic acid medicine as well as preparation method and application of nanoparticle

Abstract

The invention discloses a nanoparticle for delivering a nucleic acid drug, which comprises a nucleic acid drug, an antioxidant nano-enzyme and a carrier, the nucleic acid drug and the antioxidant nano-enzyme are loaded on the carrier, and the nucleic acid drug is a TNF-alpha targeted DNAzyme or pOTUD plasmid. The TNF-alpha targeting DNAzyme and the pOTUD plasmid are both important regulatory factors of the inflammatory bowel disease, the TNF-alpha targeting DNAzyme can specifically degrade mRNA (messenger Ribonucleic Acid) of proinflammatory TNF-alpha, and the pOTUD plasmid inhibits an NF-kappa B pathway by regulating and controlling OTUD protein expression. The nanoparticle for delivering the nucleic acid medicine simultaneously contains the nucleic acid medicine and the antioxidant nano-enzyme, the nucleic acid medicine and the antioxidant nano-enzyme generate a synergistic effect, the antioxidant nano-enzyme can remove redundant ROS at the colon lesion position, meanwhile, the biological activity of the nucleic acid medicine can be maintained in the inflammatory microenvironment, and the anti-inflammatory effect of the nucleic acid medicine is improved. The two can synergistically exert an anti-inflammatory effect in an inflammatory microenvironment.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a nanoparticle for delivering nucleic acid drugs, its preparation method, and its application. Background Technology

[0002] Inflammatory bowel disease (IBD) is a chronic inflammatory disease whose core pathological feature is intestinal microenvironment dysbiosis, involving metabolic imbalances among intestinal epithelial cells, immune cells, and the gut microbiota. References 1 (SA Hendler, BLCohen, J.-F. Colombel, BE Sands, L. Mayer, S. Agarwal, J. Crohns Colitis 9(2015) 266–275.) and 2 (J. Moreau, E. Mas, Curr. Opin. Pharm. 25 (2015) 56–61.) point out that current mainstream therapies (such as 5-aminosalicylic acid, immunosuppressants, and biologics) mainly target single factors or downstream inflammatory mediators (such as TNF-α and IL-6), and suffer from problems such as lack of target specificity, short intestinal residence time, and the need for high-dose, high-frequency administration. These therapies are prone to causing systemic adverse reactions such as myelosuppression, hepatotoxicity, nephrotoxicity, and drug resistance, resulting in unsatisfactory overall efficacy.

[0003] Nanozymes are nanomaterials with activity similar to natural enzymes, primarily belonging to heterogeneous catalysts, such as metal, metal oxide, or carbon-based nanozymes. Compared to natural enzymes, nanozymes possess superior stability and economic value. Their small size and high specific surface area help enhance tissue permeability, but require suitable carriers to reduce toxicity; simultaneously, nanozymes can improve oxidative stress, scavenge reactive oxygen species, and modulate the local immune system.

[0004] Inflammatory bowel disease (IBD) patients often produce excessive reactive oxygen species (ROS) in the inflamed colon tissue. ROS directly oxidize nucleic acid drugs (such as DNAzymes and pOTUD plasmids), causing them to lose their activity. Therefore, nucleic acid drugs in inflamed colon tissue have poor stability, which seriously hinders the clinical translation of bioactive organic molecules in the treatment of IBD.

[0005] Patent CN119970640A discloses a novel nucleic acid delivery system based on phosphatidylmitoxantrone (PMA), its preparation method, and its applications. This delivery system achieves synergistic delivery of nucleic acid drugs and chemotherapeutic drugs by combining mitoxantrone with phospholipids to form PMA, thereby significantly enhancing antitumor effects. However, the system's functional design primarily focuses on drug synergy and fails to integrate antioxidant protection mechanisms, which to some extent limits its application in oxidative stress microenvironments.

[0006] Therefore, there is an urgent need to find nanoparticles that can be used to deliver nucleic acid drugs while avoiding the oxidation and loss of activity of the nucleic acid drugs. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention provides nanoparticles for delivering nucleic acid drugs, which simultaneously contain both nucleic acid drugs and antioxidant nanozymes. The two work synergistically, with the antioxidant nanozymes clearing excess ROS at the site of colonic lesions and enabling the nucleic acid drugs to maintain their biological activity in the inflammatory microenvironment. The two can synergistically exert anti-inflammatory effects in the inflammatory microenvironment.

[0008] A nanoparticle for delivering nucleic acid drugs includes a nucleic acid drug, an antioxidant nanozyme, and a carrier, wherein the nucleic acid drug and the antioxidant nanozyme are loaded on the carrier, and the nucleic acid drug is a DNAzyme or pOTUD plasmid targeting TNF-α.

[0009] In this invention, both the DNAzyme targeting TNF-α and the pOTUD plasmid are important regulators of inflammatory bowel disease (IBD). The DNAzyme targeting TNF-α can specifically degrade pro-inflammatory TNF-α mRNA, while the pOTUD plasmid inhibits the NF-κB pathway by regulating OTUD protein expression. However, in the oxidative stress microenvironment of colonic tissue in IBD patients, the DNAzyme targeting TNF-α or the pOTUD plasmid can be oxidized by ROS, thereby losing its activity.

[0010] Antioxidant nanozymes can mimic the properties of catalase and superoxide dismutase, enabling the removal of highly reactive oxygen free radicals at the lesion site, thereby reducing inflammation at the lesion site.

[0011] The nanoparticles for delivering nucleic acid drugs in this invention contain both nucleic acid drugs and antioxidant nanozymes, which work synergistically. The antioxidant nanozymes can remove excess ROS at the site of colonic lesions, while also enabling the nucleic acid drugs to maintain their biological activity in the inflammatory microenvironment. The two can work together to exert anti-inflammatory effects in the inflammatory microenvironment.

[0012] Preferably, the total mass ratio of the nucleic acid drug and the antioxidant nanozyme to the carrier is 1:1 to 6.

[0013] Preferably, the mass ratio of the nucleic acid drug to the antioxidant nanozyme is 1~200:300 μg / mg.

[0014] Preferably, the antioxidant nanoenzyme is at least one of platinum nanoenzyme, iridium nanoenzyme, and ruthenium nanoenzyme.

[0015] Preferably, the carrier is at least one of metal-organic frameworks, liposomes, hydrogels, micelles, and polymer vesicles.

[0016] More preferably, the carrier is a metal-organic framework.

[0017] In this invention, when the carrier is a metal-organic framework, there is a significant synergistic effect between it and the loaded nucleic acid drug, specifically reflected in the introduction of Zn into the metal-organic framework. 2+ It can serve as a cofactor essential for the catalytic activity of DNAzymes targeting TNF-α, providing a key guarantee for their efficient molecular function; this vector provides an effective barrier for the pOTUD1 plasmid, significantly enhancing its resistance to degradation by nucleases (such as DNase I).

[0018] Preferably, the nanoparticles used for delivering nucleic acid drugs have a particle size of 100~1000 nm.

[0019] The present invention also provides a method for preparing the above-mentioned nanoparticles for delivering nucleic acid drugs, comprising the following steps: (1) The mixed solution of metal salt and capping agent is heated and reacted, and then precipitated by a poor solvent to obtain antioxidant nanozyme; (2) Nucleic acid drugs and antioxidant nanozymes are loaded onto a carrier to obtain nanoparticles for delivering nucleic acid drugs.

[0020] Preferably, in step (1), the metal salt is at least one of chloroplatinic acid, iridium chloride, and ruthenium chloride.

[0021] Preferably, in step (1), the capping agent is at least one of polyvinylpyrrolidone, glutathione, polyethylene glycol and triethanolamine.

[0022] Preferably, in step (1), the mass ratio of the metal salt to the capping agent is 1:6~15.

[0023] Preferably, in step (1), the undesirable solvent is at least one of anhydrous diethyl ether, dimethyl sulfoxide, N,N-dimethylformamide, and acetone.

[0024] Preferably, in step (1), the particle size of the antioxidant nanozyme is 1~20 nm.

[0025] This invention also provides the application of the above-mentioned nanoparticles for delivering nucleic acid drugs in the preparation of drugs for treating and / or diagnosing inflammatory bowel disease. The nanoparticles of this invention combine the anti-inflammatory capabilities of nucleic acid drugs with the ROS scavenging capabilities of antioxidant nanozymes, reducing inflammation at the lesion site and enhancing the antioxidant capacity of nucleic acid drugs. Simultaneously, by integrating antioxidant nanozymes and carrier structures, the nanoparticles for delivering nucleic acid drugs solve the delivery challenges of nucleic acid drugs in oxidative microenvironments, achieving spatiotemporal synergy between delivery and ROS scavenging.

[0026] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The nanoparticles for delivering nucleic acid drugs of the present invention combine an antioxidant nanozyme for scavenging ROS with a nucleic acid drug for inhibiting inflammation-related pathways. By utilizing the ROS scavenging ability of the antioxidant nanozyme, the activity of the nucleic acid drug is maintained, the antioxidant capacity of the nucleic acid drug is enhanced, and inflammation at the lesion site is reduced. By integrating the antioxidant nanozyme and the nanocarrier structure, the delivery problem of nucleic acid drugs in the oxidative microenvironment is solved, and the spatiotemporal synergy of delivery and ROS scavenging is achieved.

[0027] (2) The preparation method provided by the present invention is simple and time-saving. Attached Figure Description

[0028] Figure 1 Transmission electron microscopy images of the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2, where A and B are images corresponding to Examples 1 and 2, respectively.

[0029] Figure 2 The particle size distribution diagrams are for the nanoparticles prepared in Examples 1 and 2 for delivering nucleic acid drugs, where A and B are the particle size distribution diagrams corresponding to Examples 1 and 2, respectively.

[0030] Figure 3 This is a schematic diagram of the ABTS free radical scavenging experiment.

[0031] Figure 4 Nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2 at different concentrations for ABTS + The graph shows the free radical scavenging efficiency, where A and B are the test results for Examples 1 and 2, respectively.

[0032] Figure 5 The graphs show the antioxidant capacity of the nanoparticles prepared in Examples 1 and 2 for delivering nucleic acid drugs, and the nanoparticles in Comparative Examples 1 and 2 that are loaded only with DNAzyme targeting TNF-α or only with pOTUD plasmid. In the graphs, A represents the corresponding test results for Example 1 and Comparative Example 1, and B represents the corresponding test results for Example 2 and Comparative Example 2.

[0033] Figure 6 This is a graph evaluating the physical barrier protection performance of the nanoparticles prepared in Example 1 for delivering DNAzymes targeting TNF-α.

[0034] Figure 7The disease activity index and body weight statistics are shown for the nanoparticles prepared in Examples 1 and 2 for delivering nucleic acid drugs and the nanoparticles prepared in Comparative Example 3 that are loaded only with antioxidant nanozymes. A and B are the disease activity index statistics and body weight statistics, respectively.

[0035] Figure 8 The colon length statistics are shown for the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2 and the nanoparticles loaded only with antioxidant nanozymes prepared in Comparative Example 3. Detailed Implementation

[0036] The present invention will be further described in detail below with reference to the embodiments, but the implementation of the present invention is not limited to the following embodiments.

[0037] All raw materials used in this invention are commercially available.

[0038] Preparation method of pOTUD plasmid: The plasmid encoding pOTUD 1 was constructed by Shanghai Jikai Gene Medical Technology Co., Ltd., and all plasmids were confirmed by DNA sequencing. The obtained plasmids were transfected into *E. coli* using Lipofectamine 3000 reagent (Invitrogen, Carlsbad, CA, USA). The transformed *E. coli* cells were grown in LB medium at 37 °C for 24 h, with ampicillin added at a 1:100 ratio to maintain plasmid stability. Subsequently, bacterial cells were collected by centrifugation and resuspended in buffer solution. The plasmid was extracted using the EZgene™ EndoFree Plasmid ezFlow Miniprep Kit II (Company: Beiwo Medical, Catalog No.: BW-PD1222). Finally, the concentration and purity of the plasmid were determined using a NanoDrop spectrophotometer to ensure its quality met the requirements for subsequent experiments.

[0039] Example 1 IDZ (1) Preparation of antioxidant nanozymes One part by weight of iridium chloride and 20 parts by weight of polyvinylpyrrolidone (58000 Da) were dissolved in 200 parts by weight of polyethylene glycol and stirred at room temperature for 15 minutes. The mixture was then heated to 180 °C and stirred for 30 minutes. The iridium nanozyme was obtained by precipitation with acetone and centrifugation.

[0040] (2) Nanoparticles for delivering nucleic acid drugs By volume, 1 part iridium nanozyme (150 mg / mL) and 0.5 parts TNF-α-targeting DNAzyme (purchased from Genscript Biotech, 10 μM, i.e., 182.8 μg / mL) were added to 18 parts imidazole solution (280 mg / mL). The mixture was stirred at room temperature for 15 minutes to ensure complete dispersion. Then, 2 parts zinc nitrate solution (90 mg / mL) were added dropwise, and the mixture was allowed to stand at 4 °C for 12 hours. The nanoparticles for delivering the DNAzyme were then obtained by centrifugation (8000 rpm, 20 min) with deionized water multiple times.

[0041] Example 2 IPZ (1) Preparation of antioxidant nanozymes One part by weight of iridium chloride and 20 parts by weight of polyvinylpyrrolidone (58000 Da) were dissolved in 200 parts by weight of polyethylene glycol and stirred at room temperature for 15 minutes. The mixture was then heated to 180 °C and stirred for 30 minutes. The iridium nanozyme was obtained by precipitation with acetone and centrifugation.

[0042] (2) Nanoparticles for delivering nucleic acid drugs By volume, 1 part iridium nanozyme (150 mg / mL) and 0.5 part pOTUD plasmid (1 μg / mL) were added to 18 parts imidazole solution (280 mg / mL), and stirred at room temperature for 15 minutes to ensure complete dispersion. Then, 2 parts zinc nitrate solution (90 mg / mL) were added dropwise, and the mixture was allowed to stand at 4 °C for 12 hours. The nanoparticles for delivering the pOTUD plasmid were then obtained by centrifugation (8000 rpm, 20 min) with deionized water multiple times.

[0043] Comparative Example 1 IZ By volume, 0.5 parts of TNF-α-targeting DNAzyme (purchased from Genscript Biotech, 10 μM) were added to 18 parts of imidazole solution (280 mg / mL), and stirred at room temperature for 15 minutes to ensure complete dispersion. Then, 2 parts of zinc nitrate solution (90 mg / mL) were added dropwise, and the mixture was allowed to stand at 4 °C for 12 hours. Subsequently, the nanoparticles loaded only with DNAzyme were obtained by centrifugation (8000 rpm, 20 min) with deionized water multiple times.

[0044] Comparative Example 2 By volume, 0.5 parts of pOTUD plasmid (1 μg / mL) were added to 18 parts of imidazole solution (280 mg / mL), and stirred at room temperature for 15 minutes to ensure complete dispersion. Then, 2 parts of zinc nitrate solution (90 mg / mL) were added dropwise, and the mixture was allowed to stand at 4 °C for 12 hours. The nanoparticles loaded only with pOTUD plasmid were then obtained by centrifugation (8000 rpm, 20 min) with deionized water multiple times.

[0045] Comparative Example 3 Preparation of antioxidant nanozymes One part by weight of iridium chloride and 20 parts by weight of polyvinylpyrrolidone (58000 Da) were dissolved in 200 parts by weight of polyethylene glycol and stirred at room temperature for 15 minutes. The mixture was then heated to 180 °C and stirred for 30 minutes. The iridium nanozyme was obtained by precipitation with acetone and centrifugation.

[0046] (2) Nanoparticles for delivering nucleic acid drugs One part by volume of iridium nanozyme (150 mg / mL) was added to 18 parts by volume of imidazole solution (280 mg / mL), and stirred at room temperature for 15 minutes to ensure complete dispersion. Then, two parts by volume of zinc nitrate solution (90 mg / mL) were added dropwise, and the mixture was allowed to stand at 4 °C for 12 hours. The nanoparticles loaded only with antioxidant nanozyme were then obtained by centrifugation (8000 rpm, 20 min) with deionized water multiple times.

[0047] Sample Analysis I. Transmission electron microscopy and particle size analysis The nanoparticles prepared in Examples 1 and 2 for delivering nucleic acid drugs were analyzed by transmission electron microscopy and dynamic light scattering (DLS).

[0048] Figure 1 Transmission electron microscopy (TEM) images of the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2, where A and B are images corresponding to Examples 1 and 2, respectively. As shown in the figures, the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2 exhibit a cubic structure and good dispersibility and uniformity.

[0049] Figure 2 The figures show the particle size distribution of the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2, where A and B are the particle size distributions for Examples 1 and 2, respectively. As shown in the figures, the particle sizes of the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2 are all distributed in the range of 100–1000 nm, further verifying their good dispersibility and uniformity.

[0050] II. Free radical scavenging ability test like Figure 3As shown, ABTS (i.e., 2,2'-azido-bis-(3-ethylbenzothiazoline-6-sulfonic acid)) is oxidized by reactive oxygen species to generate stable blue-green cationic free radicals ABTS. + • Contains ABTS + • The free radical ion solution turns blue-green after oxidation. Adding free radical scavengers or antioxidants, along with ABTS... + The reaction caused the system to decolorize.

[0051] The nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2 were combined with ABTS. + • Free radical solution and incubate for 1 hour. After incubation, measure the absorbance at a wavelength of 734 nm to calculate ABTS. + • Cleaning efficiency. ABTS + • Clearance rate calculation formula: in, Indicates ABTS + Free radical solutions without added antioxidants Indicates ABTS + • Free radical solution after reaction with NENFpro at the corresponding concentration.

[0052] Figure 4 Nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2 at different concentrations for ABTS + The graph shows the free radical scavenging efficiency, where A and B represent the test results for Examples 1 and 2, respectively. As shown in the figure, the nanoparticles prepared in Examples 1 and 2 for delivering nucleic acid drugs can achieve ABTS (Alternative Radical Scavenging and Tolerancing). + Highly efficient free radical scavenging, with the nanoparticles prepared in Example 2 for delivering pOTUD plasmids exhibiting superior free radical scavenging ability.

[0053] III. Antioxidant Capacity Assessment The nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2, as well as the nanoparticles in Comparative Examples 1 and 2 loaded only with DNAzymes targeting TNF-α or only with pOTUD plasmids, were exposed to PBS or H2O2 (200 μM) and incubated at 37 °C for 30 min. Raman spectroscopy measurements were then performed using a WITec alpha 300RA confocal Raman microscope equipped with a 532 nm laser. Simultaneously, 200 μL of sample was placed in a quartz cuvette with an optical path of 1 mm, and the CD value was measured at room temperature using a Chirascan V100 spectrophotometer.

[0054] Figure 5The graphs show the antioxidant capacity test results of the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2, and the nanoparticles in Comparative Examples 1 and 2 loaded only with DNAzymes targeting TNF-α or only with pOTUD plasmids. In the graphs, A represents the test results for Example 1 and Comparative Example 1, and B represents the test results for Example 2 and Comparative Example 2. As shown in the graphs, compared with the nanoparticles loaded only with DNAzymes targeting TNF-α or only with pOTUD plasmids, the bioactivity of the DNAzymes targeting TNF-α or pOTUD plasmids in the nanoparticles prepared in Example 1 and for delivering nucleic acid drugs is protected. This is due to the action of the antioxidant nanozymes, indicating that the nanoparticles for delivering nucleic acid drugs in this invention possess antioxidant protective effects against DNAzymes or pOTUD plasmids targeting TNF-α.

[0055] IV. Evaluation of the protective performance of physical barriers The nanoparticles for delivering DNAzymes targeting TNF-α prepared in Example 1 were incubated with PBS or DNase I (2 μM) at 37 °C for 6 hours, with a DNase group serving as a control. After incubation, both groups of samples were redispersed in FAM and BHQ1-labeled mRNA substrate solutions (20 nM). After incubation for 30 minutes, excitation was performed at 490 nm, and emission was observed at 518 nm; FAM fluorescence was detected.

[0056] Figure 6 The figure shows the physical barrier protection performance evaluation of the nanoparticles prepared in Example 1 for delivering DNAzymes targeting TNF-α. As shown in the figure, the bioactivity of the DNAzyme targeting TNF-α was protected by deoxyribonuclease (DNase I) in the nanoparticles prepared in Example 1 for delivering DNAzymes targeting TNF-α. However, due to the lack of carrier protection, the DNAzyme targeting TNF-α directly underwent enzymatic hydrolysis with deoxyribonuclease (DNase I), and the structure of the DNAzyme targeting TNF-α was destroyed. This confirms the physical barrier protection performance of the nanoparticles prepared in this invention for delivering DNAzymes targeting TNF-α against nucleic acid drugs.

[0057] Application example: Evaluation of the therapeutic effects of Examples 1 and 2 and Comparative Example 3 The nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2, and the nanoparticles loaded only with antioxidant nanozymes prepared in Comparative Example 3, were dispersed in physiological saline to obtain a nanocarrier solution. Twenty-five 8-week-old C57BL / 6 mice (adapted for one week) were randomly divided into five groups of five mice each, including a control group, a 2.5% dextran sulfate sodium (DSS) induced model group, and a nanoparticle solution (10 mg / kg) treatment group. The different treatments for the five groups of mice are as follows: Control group mice: drank only water throughout the experiment; Model group mice: drank 2.5% sodium dextran sulfate (DSS) solution for 7 consecutive days; Mice in the treatment group were given 2.5% sodium dextran sulfate (DSS) for 7 consecutive days, and the nanocarrier solution (10 mg / kg) was administered rectally on days 1, 3, 5 and 7, respectively. Daily changes in mouse weight, fecal consistency, and fecal occult blood were recorded. After model establishment, mice were euthanized under deep anesthesia by cervical dislocation, and colon tissue was dissected to measure the length of the colon in each group.

[0058] Figure 7 The figures show disease activity index and body weight statistics for the nanoparticles prepared in Examples 1 and 2 for delivering nucleic acid drugs, and for the nanoparticles prepared in Comparative Example 3 that are loaded only with antioxidant nanozymes. Figures A and B show the disease activity index and body weight statistics, respectively. As shown in the figures, compared to the model group mice, the treatments in Examples 1 and 2 significantly improved the increase in disease activity index and weight loss in mice induced by DSS-induced colitis. Due to the lack of synergistic treatment with nucleic acid drugs, Comparative Example 3 mice showed remission.

[0059] Figure 8 The colon length statistics of the nanoparticles for delivering nucleic acid drugs prepared in Examples 1 and 2 and the nanoparticles loaded only with antioxidant nanozymes prepared in Comparative Example 3 are shown in the figure. Compared with the model group mice, the treatments in Examples 1 and 2 improved the shortening of colon length in mice caused by DSS-induced colitis.

[0060] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A nanoparticle for delivering nucleic acid drugs, characterized in that, It includes nucleic acid drugs, antioxidant nanozymes, and carriers, wherein the nucleic acid drugs and antioxidant nanozymes are loaded on the carriers, and the nucleic acid drugs are DNAzymes or pOTUD plasmids targeting TNF-α.

2. The nanoparticles for delivering nucleic acid drugs according to claim 1, characterized in that, The total mass ratio of the nucleic acid drug and the antioxidant nanozyme to the carrier is 1:1~6.

3. The nanoparticles for delivering nucleic acid drugs according to claim 1, characterized in that, The mass ratio of the nucleic acid drug to the antioxidant nanozyme is 1~200:300 μg / mg.

4. The nanoparticles for delivering nucleic acid drugs according to claim 1, characterized in that, The antioxidant nanozyme is at least one of platinum nanozyme, iridium nanozyme, and ruthenium nanozyme; the carrier is at least one of metal-organic framework, liposome, hydrogel, micelle, and polymer vesicle.

5. The nanoparticles for delivering nucleic acid drugs according to claim 1, characterized in that, The nanoparticles used for delivering nucleic acid drugs have a particle size of 100~1000 nm.

6. The method for preparing nanoparticles for delivering nucleic acid drugs according to any one of claims 1 to 5, characterized in that, Includes the following steps: (1) The mixed solution of metal salt and capping agent is heated and reacted, and then precipitated by a poor solvent to obtain antioxidant nanozyme; (2) Nucleic acid drugs and antioxidant nanozymes are loaded onto a carrier to obtain nanoparticles for delivering nucleic acid drugs.

7. The method for preparing nanoparticles for delivering nucleic acid drugs according to claim 6, characterized in that, In step (1), the metal salt is at least one of chloroplatinic acid, iridium chloride and ruthenium chloride; the capping agent is at least one of polyvinylpyrrolidone, glutathione, polyethylene glycol and triethanolamine; and the unsuitable solvent is at least one of anhydrous diethyl ether, dimethyl sulfoxide, N,N-dimethylformamide and acetone.

8. The method for preparing nanoparticles for delivering nucleic acid drugs according to claim 6, characterized in that, In step (1), the mass ratio of the metal salt to the capping agent is 1:6~15.

9. The method for preparing nanoparticles for delivering nucleic acid drugs according to claim 6, characterized in that, In step (1), the particle size of the antioxidant nanozyme is 1~20 nm.

10. The use of the nanoparticles for delivering nucleic acid drugs according to any one of claims 1 to 5 in the preparation of drugs for treating and / or diagnosing inflammatory bowel disease.

Images