Bionic naringenin polydopamine nanoparticles and application thereof
Through nano-encapsulation technology and membrane engineering technology, bionic naringenin polydopamine nanoparticles were prepared, and neutrophils were used as delivery vehicles to solve the problems of naringenin's insolubleness and low bioavailability, significantly improving its effectiveness in the treatment of thoracic aortic aneurysms and dissections.
Patent Information
- Application Number
- CN202411862153.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-17
- Publication Date
- 2025-03-18
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
In the prior art, naringenin, as a hard-soluble drug, has a low drug utilization rate, resulting in poor efficacy in the treatment of thoracic aortic aneurysms and dissections, and there is a risk of drug loss and adverse reactions.
Through nano-encapsulation technology, bionic naringenin polydopamine nanoparticles are prepared, and neutrophils are used as drug delivery carriers to improve the bioavailability and targeting of drugs through membrane engineering technology.
It significantly improves the drug concentration of naringenin in the lesions of thoracic aortic aneurysms and dissection, improves the bioavailability and therapeutic effect of the drug, and reduces the toxic side effects of the drug.
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Figure CN119633134A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of biomedicine, and in particular to biomimetic naringenin polydopamine nanoparticles and applications thereof. Background Art
[0002] With the continuous progress in the field of biopharmaceutical manufacturing and the continuous development of the manufacturing technology of pharmaceutical excipients and packaging materials closely related to it, the treatment strategies for cardiovascular diseases, especially aortic dilatation diseases such as thoracic aortic aneurysm and dissection (TAAD), are facing unprecedented challenges and opportunities.
[0003] Aortic dilatation, especially thoracic aortic aneurysm and dissection (TAAD), is a cardiovascular disease with a high mortality rate. Aortic aneurysm manifests as local or diffuse dilatation and can evolve into acute aortic dissection. Currently, there is no effective drug to improve the growth or rupture of aortic aneurysms, and surgery is still the main treatment principle. Therefore, the study of drug controlled release systems targeting aortic lesions has become a hot topic in the clinical treatment of TAAD.
[0004] Naringenin is a natural flavonoid with anti-inflammatory and antioxidant activities. It also has potential medicinal effects in various cardiovascular complications such as dyslipidemia, diabetes and atherosclerosis. At present, research teams have found that naringenin can inhibit the occurrence and development of abdominal aortic aneurysms in animal models. In addition, naringenin is a poorly soluble drug with low drug utilization after administration, which can easily lead to drug loss and waste, and increase the risk of adverse events, thus greatly limiting its medicinal effects and wide application. In order to solve this problem, it was found that the solubility and bioavailability of naringenin can be improved by nanoencapsulation technology, thereby improving its effectiveness and safety. However, naringenin nanoparticles are currently rare in the drug treatment of thoracic aortic aneurysms and dissections.
[0005] Mesoporous polydopamine nanoparticles are nanomaterials with mesoporous structures and dopamine chemical properties. The surface of this nanoparticle has abundant micropores and channels, providing a large specific surface area. Dopamine is a molecule that exists naturally in organisms. Polydopamine nanoparticles are aggregated from dopamine monomers and have good biocompatibility and biological interaction capabilities. Nano drug delivery systems have attracted much attention due to their large specific surface area and the ability to improve drug distribution and metabolism, reduce drug toxicity and side effects, and enhance tumor targeting. However, the increase in drug content of nano drugs in lesions is still limited. Exploring and developing new targeting strategies is of great significance for promoting the safe and efficient accumulation of drugs in target tissues and organs, thereby improving the efficacy of drugs for related diseases.
[0006] Nano-delivery technology based on cell membrane engineering uses endogenous living cells as functional materials to coat the surface of nano-drugs, giving them the natural properties of cell membranes, which can effectively combine the essential properties of organisms with the advantages of artificial nano-materials. This technology can not only improve the pharmacokinetic properties of nano-drugs in the body, but also give nano-drugs stronger biological targeting capabilities, allowing drugs to selectively aggregate at disease sites, thereby improving the bioavailability of drugs and the medication effect of the disease, and overcome the shortcomings of traditional nano-delivery systems such as short circulation time, low biocompatibility and poor immunogenicity.
[0007] Neutrophils, as the most abundant white blood cells in human blood circulation, have an inherent ability to home to inflammation / tumor areas. Compared with traditional nanodiagnosis and treatment technologies, neutrophils significantly increase the concentration of nanoparticles at the disease site and can improve the limitations of low immunogenicity and biocompatibility of traditional nanodelivery systems. Therefore, neutrophils were further used to construct membrane-engineered biomimetic naringenin polydopamine nanoparticles to improve the targeted therapeutic effect of naringenin on thoracic aortic aneurysms and dissections.
[0008] In summary, obtaining a bionic naringenin-polydopamine nanoparticle and its application are of great significance. Summary of the invention
[0009] The purpose of the present invention is to provide a bionic naringenin polydopamine nanoparticle and application thereof to solve the problems raised in the prior art.
[0010] To achieve the above object, the present invention provides the following technical solutions:
[0011] A bionic naringenin polydopamine nanoparticle comprises the following steps:
[0012] Step 1: dissolving Pluronic and dopamine hydrochloride in an ethanol aqueous solution, then adding 3,3',5,5'-tetramethylbenzidine solution, and ultrasonically treating for 5 to 15 minutes; adjusting the pH to 7.5 to 8.5, vigorously stirring at room temperature for 3 to 5 hours, and collecting the precipitate by centrifugation to obtain mesoporous polydopamine nanoparticles, and storing them at 0 to 5°C for standby use;
[0013] Step 2: adding mesoporous polydopamine nanoparticles to anhydrous ethanol for dissolution, adding naringenin, ultrasonically treating for 2 to 10 minutes, then stirring at 20 to 30° C. for 4 to 12 hours, and collecting the precipitate by centrifugation to obtain naringenin polydopamine nanoparticles;
[0014] Step 3: co-incubate the naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
[0015] More optimally, the raw materials of the mesoporous polydopamine nanoparticles include the following components: 100-200 parts of Pluronic and 25-50 parts of dopamine hydrochloride, by mass.
[0016] In a further embodiment, the Pluronic is F127, and the 3,3',5,5'-tetramethylbenzidine solution is TMB solution.
[0017] More optimally, in the raw material of the naringenin polydopamine nanoparticles, the mass ratio of the mesoporous polydopamine nanoparticles to naringenin is 1:2-6.
[0018] More optimally, the preparation method of the bionic naringenin polydopamine nanoparticles is:
[0019] Step 1: adding naringenin polydopamine nanoparticles and 2-(aminomethyl)isonicotinamide to ethyl acetate, stirring at room temperature until the solvent is completely volatilized, and vacuum drying to obtain modified naringenin polydopamine nanoparticles;
[0020] Step 2: adding the modified chitosan to a 1-1.5 wt% acetic acid aqueous solution, stirring at room temperature overnight to obtain a modified chitosan solution; adding the modified naringenin polydopamine nanoparticles to a 0.5-0.6 wt% acetic acid aqueous solution, and dripping the modified chitosan solution; stirring at room temperature for 6-8 hours; collecting the precipitate by centrifugation, and freeze-drying to obtain composite naringenin polydopamine nanoparticles;
[0021] Step 3: co-incubating the modified naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
[0022] More optimally, in the raw materials of the modified naringenin polydopamine nanoparticles, the mass ratio of naringenin polydopamine nanoparticles, 2-(aminomethyl)isonicotinamide, and ethyl acetate is 1:0.05-0.08:40-50;
[0023] In the raw materials of the composite naringenin polydopamine nanoparticles, the mass ratio of modified chitosan to modified naringenin polydopamine nanoparticles is 0.5-0.6:5.
[0024] More optimally, the preparation method of the modified chitosan is:
[0025] Step 1: adding chitosan to N,N-dimethylformamide and swelling for 1 to 3 hours to obtain a mixed solution A;
[0026] Step 2: Add hyaluronic acid, monocarboxyl polyethylene glycol, 4-dimethylaminopyridine and dicyclohexylcarbodiimide to N,N-dimethylformamide, add mixed solution A, react at 0-5°C for 1-3 hours and then at 20-30°C for 20-28 hours, filter, wash, and purify by dialyzing to obtain modified chitosan.
[0027] More optimally, in the raw materials of the mixed solution A, the mass ratio of chitosan to N,N-dimethylformamide is 2-3:25-30;
[0028] The raw materials of the modified chitosan include, by weight, 3 to 4 parts of hyaluronic acid, 3 to 4 parts of monocarboxyl polyethylene glycol, 0.2 to 0.5 parts of 4-dimethylaminopyridine, 30 to 40 parts of N,N-dimethylformamide, 2 to 4 parts of dicyclohexylcarbodiimide, and 25 to 30 parts of mixed solution A.
[0029] Among them, chitosan is modified, carboxyl groups and amino groups form an amidation reaction, and hyaluronic acid and hydroxyl groups are introduced. The introduction of hyaluronic acid is to utilize its property of binding to CD-44 receptors highly expressed by tumor cells to achieve active tumor-targeted delivery of nanoparticles. The introduction of hydroxyl groups is to further improve the properties of chitosan-coated mesoporous polydopamine nanoparticles, by enhancing hydrophilicity, stability or interaction with other biological molecules, synergizing with hyaluronic acid, and jointly optimizing the behavior of nanoparticles in vivo, reducing nonspecific adsorption, and improving targeting efficiency, thereby enhancing the overall therapeutic effect and bioavailability.
[0030] Through physical and chemical adsorption of naringenin, the modified chitosan is wrapped in the outermost layer. The modified chitosan improves biocompatibility and biodegradability, and enhances water solubility. The modified chitosan modifies the naringenin polydopamine nanoparticles to make them positively charged, which helps to increase the adhesion of the nanoparticles to tumor cells, improve the accumulation and penetration of the nanoparticles in tumor tissues, and thus enhance the therapeutic effect. Due to the outer layer of chitosan, the nanoparticles gradually decompose the chitosan and polydopamine layers in the body, and accurately regulate the delivery and release process of naringenin in the body.
[0031] Application of bionic naringenin polydopamine nanoparticles, and application of the bionic naringenin polydopamine nanoparticles in drugs for treating thoracic aortic aneurysms.
[0032] Compared with the prior art, the present invention has the following beneficial effects:
[0033] (1) The present invention uses natural non-toxic materials such as naringenin, dopamine, and neutrophils to prepare membrane-engineered biomimetic naringenin polydopamine nanoparticles. The nanoparticles achieve a high drug encapsulation rate and drug loading rate and are non-toxic to cells. The present invention constructs a neutrophil-based biomimetic naringenin nanodelivery system that can target the lesion site of the thoracic aorta to improve the absorption and utilization rate of naringenin and reduce the toxic and side effects of the drug.
[0034] (2) The present invention proposes the use of bionic naringenin polydopamine nanoparticles in drugs for treating thoracic aortic aneurysms. The present invention uses neutrophils as drug delivery carriers and constructs membrane-engineered bionic naringenin polydopamine nanoparticles to enable naringenin to recognize and target the lesion site of thoracic aortic dilatation, thereby significantly improving the pertinence and effect of medicinal treatment.
[0035] (3) In order to further improve the bioavailability of naringenin in the biomimetic naringenin polydopamine nanoparticles; before incubation with neutrophils, the composite naringenin polydopamine nanoparticles were further modified by eutectic treatment with 2-(aminomethyl)isonicotinamide and encapsulation treatment with modified chitosan, which can promote the inhibitory effect of naringenin and improve the efficacy of naringenin. In addition, the stability and dispersibility of the nanoparticles can be enhanced, and their biocompatibility, targeting, and encapsulation rate can be improved, thereby improving the overall bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS
[0036] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:
[0037] Figure 1 Synthesis route for biomimetic naringenin-polydopamine nanoparticles. DETAILED DESCRIPTION
[0038] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0039] It should be noted that the raw materials involved in the present invention are commercially available.
[0040] In the following embodiments, it is particularly noted that the co-incubation process of naringenin polydopamine nanoparticles and neutrophils is specifically as follows:
[0041] Step 1: First, place the neutrophils in DMEM high-glucose medium with a serum concentration of 10wt% at 37°C and 5wt% CO 2 When the cells grow to about 80wt% in the culture flask, use 0.25wt% trypsin cell digestion solution to incubate at 37℃ for 1min. After digestion, quickly add 5mL complete culture solution to terminate digestion, blow the cells down thoroughly and centrifuge at 1000rpm for 5min. Carefully remove the upper culture medium from the centrifuged cells, add complete culture medium to fully resuspend, and finally add the cell suspension to a new culture flask (passage at a ratio of 1:2.5) and continue culturing.
[0042] Step 2: When the cells cover the bottom of the culture flask, take it out from the incubator and add 1 mL of 0.25 wt% trypsin for digestion. When white mist appears at the bottom of the culture flask, add 4 mL of culture medium and pipette to suspend the cells. 4 / well were inoculated into 96-well plates, and the cells were allowed to adhere to the wall and cultured for 12 hours. The cultured cells were taken out, the cell waste liquid was aspirated, and the cells were washed twice with PBS, and fresh culture medium was added. The prepared naringenin polydopamine nanoparticles were added and incubated for 12 hours. After the incubation, the cell waste liquid was aspirated, and the cells were washed twice with PBS, and 100 μL of CCK-8 solution was added, and the cells were incubated for 2 hours. The absorbance at 490 nm was detected by an enzyme marker.
[0043] In the following examples, Pluronic is F127, and the 3,3',5,5'-tetramethylbenzidine solution is TMB solution.
[0044] Example 1: A biomimetic naringenin polydopamine nanoparticle comprising the following steps:
[0045] Step 1: 0.2 g F127 (Pluronic) and 50 mg dopamine hydrochloride were dissolved in a mixed solution containing 25 ml of deionized water and 25 ml of ethanol (a total of 50 ml of the mixed solution), and then 230 μL TMB solution was added (operated in a fume hood), the power was set to 500 W, and ultrasonic treatment was performed for 10 minutes with an interval of 2 seconds after each ultrasonic treatment for 3 seconds; the pH was adjusted to 8.0, and the mixture was vigorously stirred at room temperature for 4 hours. The precipitate was collected by centrifugation to obtain mesoporous polydopamine nanoparticles, which were stored at 4°C for standby use;
[0046] Step 2: adding mesoporous polydopamine nanoparticles to anhydrous ethanol for dissolution, adding naringenin, ultrasonically treating for 5 minutes, then stirring at 25°C for 8 hours, centrifuging at a speed of 10000 rpm to collect the precipitate, the mass ratio of mesoporous polydopamine nanoparticles to naringenin is 1:2, and obtaining naringenin polydopamine nanoparticles;
[0047] Step 3: co-incubate the naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
[0048] Example 2: Based on Example 1, the modified chitosan is wrapped in the outermost layer, comprising the following steps:
[0049] Step 1: (1) Add chitosan to N,N-dimethylformamide and swell for 2 hours. The mass ratio of chitosan to N,N-dimethylformamide is 2.5:28 to obtain a mixed solution A; (2) Add 3.5 parts of hyaluronic acid, 3.5 parts of monocarboxyl polyethylene glycol, 0.3 parts of 4-dimethylaminopyridine, and 3 parts of dicyclohexylcarbodiimide to 35 parts of N,N-dimethylformamide, add 28 parts of the mixed solution A, react at 4°C for 2 hours and then at 25°C for 24 hours, filter, and wash with anhydrous ethanol 4 times to obtain modified chitosan;
[0050] Step 2: (1) Adding naringenin polydopamine nanoparticles and 2-(aminomethyl)isonicotinamide to ethyl acetate, stirring at room temperature until the solvent is completely volatilized, and vacuum drying; obtaining modified naringenin polydopamine nanoparticles, wherein the mass ratio of naringenin polydopamine nanoparticles, 2-(aminomethyl)isonicotinamide, and ethyl acetate is 1:0.06:45; (2) Adding modified chitosan to 1.2wt% acetic acid aqueous solution, stirring at room temperature overnight, obtaining a modified chitosan solution; adding modified naringenin polydopamine nanoparticles to 0.55wt% acetic acid aqueous solution, adding the modified chitosan solution dropwise; stirring at room temperature for 7 hours; collecting the precipitate by centrifugation, and freeze-drying to obtain composite naringenin polydopamine nanoparticles, wherein the mass ratio of modified chitosan to modified naringenin polydopamine nanoparticles is 0.55:5; (3) Co-incubating the modified naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
[0051] Comparative Example 1: Based on Example 2, hyaluronic acid is not added, and the other processes remain unchanged, specifically:
[0052] Step 1: (1) adding chitosan to N,N-dimethylformamide and swelling for 2 hours, wherein the mass ratio of chitosan to N,N-dimethylformamide is 2.5:28, and obtaining a mixed solution A; (2) adding 6 parts of monocarboxyl polyethylene glycol, 0.3 parts of 4-dimethylaminopyridine, and 3 parts of dicyclohexylcarbodiimide to 35 parts of N,N-dimethylformamide, adding 28 parts of the mixed solution A, reacting at 4°C for 2 hours and then at 25°C for 24 hours, filtering, and washing with anhydrous ethanol for 4 times to obtain modified chitosan;
[0053] Step 2: (1) Adding naringenin polydopamine nanoparticles and 2-(aminomethyl)isonicotinamide to ethyl acetate, stirring at room temperature until the solvent is completely volatilized, and vacuum drying; obtaining modified naringenin polydopamine nanoparticles, wherein the mass ratio of naringenin polydopamine nanoparticles, 2-(aminomethyl)isonicotinamide, and ethyl acetate is 1:0.06:45; (2) Adding modified chitosan to 1.2wt% acetic acid aqueous solution, stirring at room temperature overnight, obtaining a modified chitosan solution; adding modified naringenin polydopamine nanoparticles to 0.55wt% acetic acid aqueous solution, adding the modified chitosan solution dropwise; stirring at room temperature for 7 hours; collecting the precipitate by centrifugation, and freeze-drying to obtain composite naringenin polydopamine nanoparticles, wherein the mass ratio of modified chitosan to modified naringenin polydopamine nanoparticles is 0.55:5; (3) Co-incubating the modified naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
[0054] Comparative Example 2: Based on Example 2, monocarboxyl polyethylene glycol was not added, and the other processes remained unchanged, specifically:
[0055] Step 1: (1) adding chitosan to N,N-dimethylformamide and swelling for 2 hours, wherein the mass ratio of chitosan to N,N-dimethylformamide is 2.5:28, and obtaining a mixed solution A; (2) adding 6 parts of hyaluronic acid, 0.3 parts of 4-dimethylaminopyridine, and 3 parts of dicyclohexylcarbodiimide to 35 parts of N,N-dimethylformamide, adding 28 parts of the mixed solution A, reacting at 4°C for 2 hours and then at 25°C for 24 hours, filtering, and washing with anhydrous ethanol for 4 times to obtain modified chitosan;
[0056] Step 2: (1) Adding naringenin polydopamine nanoparticles and 2-(aminomethyl)isonicotinamide to ethyl acetate, stirring at room temperature until the solvent is completely volatilized, and vacuum drying; obtaining modified naringenin polydopamine nanoparticles, wherein the mass ratio of naringenin polydopamine nanoparticles, 2-(aminomethyl)isonicotinamide, and ethyl acetate is 1:0.06:45; (2) Adding modified chitosan to 1.2wt% acetic acid aqueous solution, stirring at room temperature overnight, obtaining a modified chitosan solution; adding modified naringenin polydopamine nanoparticles to 0.55wt% acetic acid aqueous solution, adding the modified chitosan solution dropwise; stirring at room temperature for 7 hours; collecting the precipitate by centrifugation, and freeze-drying to obtain composite naringenin polydopamine nanoparticles, wherein the mass ratio of modified chitosan to modified naringenin polydopamine nanoparticles is 0.55:5; (3) Co-incubating the modified naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
[0057] Comparative Example 3, based on Example 2, the naringenin polydopamine nanoparticles were not modified, and the other processes remained unchanged, specifically:
[0058] Step 1: (1) Add chitosan to N,N-dimethylformamide and swell for 2 hours. The mass ratio of chitosan to N,N-dimethylformamide is 2.5:28 to obtain a mixed solution A; (2) Add 3.5 parts of hyaluronic acid, 3.5 parts of monocarboxyl polyethylene glycol, 0.3 parts of 4-dimethylaminopyridine, and 3 parts of dicyclohexylcarbodiimide to 35 parts of N,N-dimethylformamide, add 28 parts of the mixed solution A, react at 4°C for 2 hours and then at 25°C for 24 hours, filter, and wash with anhydrous ethanol 4 times to obtain modified chitosan;
[0059] Step 2: (1) adding modified chitosan to a 1.2 wt% acetic acid aqueous solution, stirring at room temperature overnight to obtain a modified chitosan solution; adding naringenin polydopamine nanoparticles to a 0.55 wt% acetic acid aqueous solution, and dropping the modified chitosan solution; stirring at room temperature for 7 hours; collecting the precipitate by centrifugation, and freeze-drying to obtain composite naringenin polydopamine nanoparticles, wherein the mass ratio of the modified chitosan to the naringenin polydopamine nanoparticles is 0.55:5; (2) co-incubating the modified naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
[0060] Detection experiment: The bionic naringenin polydopamine nanoparticles prepared in Examples 1-2 and Comparative Examples 1-3 were subjected to performance testing: (1) Thermal stability study: The bionic naringenin polydopamine nanoparticles prepared in Examples 1-2 and Comparative Examples 1-3 were placed in a 50° C. light-proof water bath for testing, and the naringenin content was determined using an ultraviolet photometer on the first, third and seventh days, as shown in Table 1; (2) DPPH free radical scavenging rate test: The bionic naringenin polydopamine nanoparticles prepared in Examples 1-2 and Comparative Examples 1-3 were added to 2 ml of a 0.04 mg / ml DPPH solution, and the supernatant was centrifuged and tested at a wavelength of 517 nm, as shown in Table 1;
[0061]
[0062] Table 1
[0063] Result analysis: According to the data analysis in Table 1, it can be seen that by wrapping the modified chitosan in the outermost layer, and modifying chitosan with 2-(aminomethyl)isonicotinamide cocrystal, hyaluronic acid, and monocarboxyl polyethylene glycol, the drug efficacy is improved, and the sustained release performance of the drug and the thermal stability encapsulation rate are also effectively improved, and the antioxidant capacity is also significantly improved. The present invention constructs a neutrophil-based bionic naringenin nano-delivery system that can target the lesion site of the thoracic aorta to improve the absorption and utilization rate of naringenin and reduce the toxic and side effects of the drug.
[0064] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.
Claims
1. A bionic naringenin polydopamine nanoparticle, characterized in that: The following steps are involved: Step 1: dissolving Pluronic and dopamine hydrochloride in an ethanol aqueous solution, then adding 3,3',5,5'-tetramethylbenzidine solution, and ultrasonically treating for 5 to 15 minutes; adjusting the pH to 7.5 to 8.5, vigorously stirring at room temperature for 3 to 5 hours, and collecting the precipitate by centrifugation to obtain mesoporous polydopamine nanoparticles, and storing them at 0 to 5°C for standby use; Step 2: adding mesoporous polydopamine nanoparticles to anhydrous ethanol for dissolution, adding naringenin, ultrasonically treating for 2 to 10 minutes, then stirring at 20 to 30° C. for 4 to 12 hours, and collecting the precipitate by centrifugation to obtain naringenin polydopamine nanoparticles; Step 3: co-incubate the naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
2. The biomimetic naringenin polydopamine nanoparticle according to claim 1, characterized in that: The raw materials of the mesoporous polydopamine nanoparticles include the following components: 100 to 200 parts of Pluronic and 25 to 50 parts of dopamine hydrochloride by mass.
3. The biomimetic naringenin polydopamine nanoparticle according to claim 1, characterized in that: In the raw materials of the naringenin polydopamine nanoparticles, the mass ratio of the mesoporous polydopamine nanoparticles to naringenin is 1:2-6.
4. The bionic naringenin polydopamine nanoparticle according to claim 1, characterized in that: The preparation method of the bionic naringenin polydopamine nanoparticles is as follows: Step 1: Add naringenin polydopamine nanoparticles and 2-(aminomethyl)isonicotinamide to ethyl acetate, stir at room temperature until the solvent is completely evaporated, and vacuum dry; Modified naringenin polydopamine nanoparticles are obtained; Step 2: adding the modified chitosan to a 1-1.5 wt% acetic acid aqueous solution, stirring at room temperature overnight to obtain a modified chitosan solution; adding the modified naringenin polydopamine nanoparticles to a 0.5-0.6 wt% acetic acid aqueous solution, and dripping the modified chitosan solution; stirring at room temperature for 6-8 hours; collecting the precipitate by centrifugation, and freeze-drying to obtain composite naringenin polydopamine nanoparticles; Step 3: co-incubating the modified naringenin polydopamine nanoparticles with neutrophils to obtain biomimetic naringenin polydopamine nanoparticles.
5. The biomimetic naringenin polydopamine nanoparticle according to claim 4, characterized in that: In the raw materials of the modified naringenin polydopamine nanoparticles, the mass ratio of naringenin polydopamine nanoparticles, 2-(aminomethyl)isonicotinamide, and ethyl acetate is 1:0.05-0.08:40-50; In the raw materials of the composite naringenin polydopamine nanoparticles, the mass ratio of modified chitosan to modified naringenin polydopamine nanoparticles is 0.5-0.6:
5.
6. The bionic naringenin polydopamine nanoparticle according to claim 5, characterized in that: The preparation method of the modified chitosan is: Step 1: adding chitosan to N,N-dimethylformamide and swelling for 1 to 3 hours to obtain a mixed solution A; Step 2: Add hyaluronic acid, monocarboxyl polyethylene glycol, 4-dimethylaminopyridine and dicyclohexylcarbodiimide to N,N-dimethylformamide, add mixed solution A, react at 0-5°C for 1-3 hours and then at 20-30°C for 20-28 hours, filter, wash, and purify by dialyzing to obtain modified chitosan.
7. The biomimetic naringenin polydopamine nanoparticle according to claim 6, characterized in that: In the raw materials of the mixed solution A, the mass ratio of chitosan to N,N-dimethylformamide is 2-3:25-30; The raw materials of the modified chitosan include, by weight, 3 to 4 parts of hyaluronic acid, 3 to 4 parts of monocarboxyl polyethylene glycol, 0.2 to 0.5 parts of 4-dimethylaminopyridine, 30 to 40 parts of N,N-dimethylformamide, 2 to 4 parts of dicyclohexylcarbodiimide, and 25 to 30 parts of mixed solution A.
8. An application of bionic naringenin polydopamine nanoparticles, characterized in that: Application of the bionic naringenin polydopamine nanoparticles in drugs for treating thoracic aortic aneurysms.