COF heterojunction nanosphere with biomimetic mineralization and antibacterial functions as well as preparation method and application of COF heterojunction nanosphere

Abstract

The invention relates to the technical field of biomedical materials, in particular to a COF heterojunction nanosphere with biomimetic mineralization and antibacterial functions and a preparation method and application thereof. The preparation method comprises the following steps: mixing a magnolol solution, a 1, 3, 5-tris (4-aminophenyl) benzene solution, a polyvinylpyrrolidone solution, a 2, 5-dimethoxybenzene-1, 4-dicarboxaldehyde solution and acetic acid, so as to obtain COFDMTP-coated Honokiol nanospheres; the preparation method comprises the following steps: mixing 4, 4 '-((2, 5-diformyl-1, 4-phenylene) bis (oxy)) dibutyric acid, COFDMTP (at) Honokiol nanospheres, acetonitrile and an acetic acid solution, and reacting to obtain the COFFPBA (at) Honokiol heterojunction nanospheres. The heterojunction nanosphere provided by the invention not only can promote the mineralization of acid-etched enamel, but also can effectively inhibit the growth of oral bacteria and reduce the occurrence of decayed teeth.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a COF heterojunction nanosphere with biomimetic mineralization and antibacterial dual functions, its preparation method, and its application. Background Technology

[0002] Tooth enamel is one of the hardest tissues in the human body, primarily composed of hydroxyapatite (HAp) crystals, possessing a high degree of mineralization and a unique microstructure. However, once enamel is damaged, such as by cavities or acid erosion, it will seriously affect oral health. Caries is a common oral disease, its pathogenesis mainly stemming from bacteria in the mouth, especially Streptococcus mutans, which decompose food debris to produce acidic substances, leading to enamel demineralization and the formation of cavities. Currently, enamel restoration primarily relies on physical methods such as filling materials, including composite resins. While these methods can restore the shape and function of enamel to some extent, they cannot restore its natural structure and bioactivity. Furthermore, these materials are easily corroded in the oral environment, resulting in short-lived restorations. Fluoride-containing products can effectively promote the formation of fluorapatite, thereby achieving enamel remineralization. However, they lack the ability to form ordered, oriented fluorapatite crystals, and excessive fluoride intake can easily lead to fluorosis or even fluorosis poisoning. Therefore, achieving both antibacterial and demineralized enamel mineralization restoration using biomimetic materials remains a challenge.

[0003] The formation, growth, and maturation of enamel crystals in the human body are governed by instructions encoded by a genetic blueprint. These instructions are executed by proteins secreted into the enamel matrix, with amelogenin being a crucial matrix protein. Amelogenin plays a vital role in regulating HAp crystal morphology, size, growth direction, and enamel thickness. Amelogenin is primarily composed of tyrosine-rich N-termini and relatively short hydrophilic C-termini. Under physiological conditions, it can self-assemble into 10-20 nm nanospheres, regulating the growth direction and rate of HAp crystals. Specifically, the C-terminus provides nucleation sites for calcium phosphate and guides directional crystal growth, while the N-terminus enables the self-assembly of amelogenin, controlling the growth direction of enamel prisms. Biomimetic materials such as amino acids and dendritic macromolecules like PMMA are widely used in enamel repair research. However, the instability and easy degradation of proteins and peptides, along with the complex synthesis of dendritic PMMA, significantly limit its clinical application. Therefore, finding safe and effective biomimetic remineralization materials for the remineralization repair of early enamel caries is essential.

[0004] Covalent organic frameworks (COFs) are a class of highly crystalline, porous organic polymers whose structural building blocks are linked by covalent bonds, possessing numerous active terminal groups. On one hand, through rational monomer design and functional modification, different functions can be achieved. COFs can also form various morphologies such as nanospheres, nanofibers, and gels, and these structures are highly similar in morphology and scale to the assemblies of amelogenin, which induces the directional growth of HAp crystals. On the other hand, COFs possess an intrinsic porous structure, and the pore structure and size can be controlled, making them ideal drug-loaded materials. Through rational structural design, COFs are expected to simultaneously achieve multiple functions such as antibacterial, therapeutic, and mineralization regulation. Furthermore, the chemical stability and biocompatibility of COFs make them promising candidates for applications in the biomedical field. However, there are currently no reports on the simultaneous role of COFs in enamel mineralization and antibacterial activity. Summary of the Invention

[0005] The purpose of this invention is to provide a COF heterojunction nanosphere with biomimetic mineralization and antibacterial dual functions, its preparation method and application. This nanosphere can not only promote the mineralization of acid-etched tooth enamel, but also effectively inhibit the growth of oral bacteria and reduce the occurrence of tooth decay.

[0006] To achieve the above objectives, this invention provides a method for preparing COF heterojunction nanospheres with both biomimetic mineralization and antibacterial functions, comprising the following preparation steps: S1. Mix magnolol solution, 1,3,5-tris(4-aminophenyl)benzene solution, polyvinylpyrrolidone solution, 2,5-dimethoxybenzene-1,4-dicarboxaldehyde solution, and acetic acid to obtain COF. DMTP @Honokiol nanospheres; S2, 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid, COF DMTP Honokiol nanospheres, acetonitrile, and acetic acid solution were mixed and reacted under vacuum to yield COF. FPBA @Honokiol heterojunction nanospheres.

[0007] In this invention, the honokiol solution in S1 includes honokiol and dimethyl sulfoxide, with a mass-to-volume ratio of 20-50 mg: 1 mL; the 1,3,5-tris(4-aminophenyl)benzene solution includes 1,3,5-tris(4-aminophenyl)benzene and acetonitrile, with a mass-to-volume ratio of 10-15 mg: 2 mL.

[0008] In this invention, the preferred mass of magnolol is 30 mg, and the preferred mass of 1,3,5-tris(4-aminophenyl)benzene is 14 mg.

[0009] In this invention, the polyvinylpyrrolidone solution in S1 comprises polyvinylpyrrolidone and acetonitrile, with a mass-to-volume ratio of 3-7 mg:2 mL, and the weight-average molecular weight of polyvinylpyrrolidone is 35,000-38,000; the 2,5-dimethoxybenzene-1,4-dicarboxaldehyde solution comprises 2,5-dimethoxybenzene-1,4-dicarboxaldehyde and methanol, with a mass-to-volume ratio of 12 mg:15-20 mL.

[0010] In this invention, the preferred mass of polyvinylpyrrolidone is 5 mg.

[0011] In this invention, the mass-to-volume ratio of magnolol, 1,3,5-tris(4-aminophenyl)benzene, and acetic acid is 20-50 mg: 10-15 mg: 1 mL.

[0012] In this invention, the mass-to-volume ratio of polyvinylpyrrolidone, 2,5-dimethoxybenzene-1,4-dicarboxaldehyde, and acetic acid is 3-7 mg: 12 mg: 1 mL.

[0013] In this invention, the CAS number of magnolol is 35354-74-6, the CAS number of 1,3,5-tris(4-aminophenyl)benzene is 118727-34-7, and the CAS number of 2,5-dimethoxybenzene-1,4-dicarboxaldehyde is 7310-97-6.

[0014] In this invention, the preparation process of 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid (FPBA) in S2 includes: (1) Dissolve 1.2 mmol of 2,5-dihydroxyterephthalaldehyde and 4.8 mmol of ethyl 4-bromobutyrate in 20-30 mL of N,N-dimethylformamide, then add 4.8 mmol of potassium carbonate, and heat at 75 °C. The reaction was carried out for 12 hours. After the reaction was completed, the reaction system was extracted four times with dichloromethane and then purified by silica gel column chromatography using petroleum ether-ethyl acetate (volume ratio 5:1) as eluent to obtain the precursor FPBA-CH3. (2) Dissolve 0.3 mmol of the precursor FPBA-CH3 in 30 mL of methanol solution to obtain a precursor solution. Add 3-10 mL of sodium hydroxide solution to the precursor solution. The reaction was carried out for 12 hours. After the reaction was completed, the reaction system was rotary evaporated and cooled. Then, hydrochloric acid solution was added to adjust the pH of the reaction system to 2-3. After a pale yellow solid precipitated, it was filtered, the obtained solid product was washed, and dried under vacuum to obtain 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid.

[0015] In this invention, the structural formula of the precursor FPBA-CH3 in step (1) is: .

[0016] In this invention, the concentration of the sodium hydroxide solution in step (2) is 0.24-0.8 mol. L, the concentration of hydrochloric acid solution is 1-12 mol L.

[0017] In this invention, the structural formula of 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid is: .

[0018] In this invention, S2 contains 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid and COF DMTP The molar mass ratio of @Honokiol nanospheres is 0.62 mmol: 8-12 mg.

[0019] In this invention, COF in S2 DMTP The mass-to-volume ratio of Honokiol nanospheres, acetonitrile, and acetic acid solution is 8-12 mg: 4 mL: 40 mL. The concentration of the acetic acid solution is 10⁻¹² mol. L.

[0020] In this invention, the reaction temperature in S2 is 80-90°C. The reaction time is 70-74 hours.

[0021] In this invention, after the reaction in S2 is completed, the obtained COF DMTP @Honokiol nanospheres are in the form of a dispersion, COF DMTP @Honokiol nanospheres are uniformly dispersed in the solution.

[0022] In this invention, after the reaction in S2 is completed, COF can be obtained by drying, filtration, washing, and secondary drying. DMTP @Honokiol nanosphere powder state.

[0023] The present invention also provides COF heterojunction nanospheres with biomimetic mineralization and antibacterial dual functions prepared by the above-mentioned method for preparing COF heterojunction nanospheres with biomimetic mineralization and antibacterial dual functions.

[0024] This invention also provides the application of the above-mentioned biomimetic mineralization and antibacterial dual-function COF heterojunction nanospheres in enamel repair and oral antibacterial treatment.

[0025] The present invention has the following beneficial effects: This invention provides a method for preparing COF heterojunction nanospheres with both biomimetic mineralization and antibacterial functions, comprising the following preparation steps: S1, mixing honokiol solution, 1,3,5-tris(4-aminophenyl)benzene solution, polyvinylpyrrolidone solution, 2,5-dimethoxybenzene-1,4-dicarboxaldehyde solution, and acetic acid to obtain COF. DMTP @Honokiol nanospheres; S2, 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid, COF DMTP Honokiol nanospheres, acetonitrile, and acetic acid solution were mixed and reacted under vacuum to yield COF. FPBA @Honokiol heterojunction nanospheres.

[0026] This invention provides a method for preparing carboxyl-containing COF heterojunction nanospheres with both biomimetic mineralization and antibacterial functions using a building block reconstruction strategy. The carboxyl functional groups mimic the C-terminus of amelogenin, acting as binding sites for HAp (hypoallergenic acid) and providing nucleation sites. The nanospheres themselves and their assemblies mimic the N-terminus of amelogenin, inducing the directional growth of HAp crystals. Finally, utilizing the porous structure of COF, the antibacterial drug honokiol is loaded into the nanospheres, achieving both antibacterial and mineralization effects.

[0027] COF prepared by the method of the present invention FPBA @Honokiol heterojunction nanospheres can serve as organic templates to induce the directional and ordered growth of HAp crystals on the surfaces of various substrates (SiO2, glass, Ti6Al4V, and acid-etched enamel).

[0028] COF prepared by the method of the present invention FPBA @Honokiol heterojunction nanospheres possess hydrophobic cavities that exhibit high drug loading capacity, low cytotoxicity, good biocompatibility, strong drug release capability, and excellent structural designability and functional scalability. Their porous structure and abundant active sites provide ample room for subsequent functional modifications. In addition to existing biomimetic remineralization and antibacterial functions, further chemical modifications or drug loading can introduce novel functions such as anti-inflammatory, analgesic, and periodontal tissue regeneration promotion, further expanding their application in oral medicine and potentially leading to the development of more personalized treatment materials for various oral diseases.

[0029] The COF provided by this invention FPBA@Honokiol heterojunction nanospheres have an excellent ability to induce the formation of HAp coatings and have a strong interfacial bonding ability with the coatings, which makes it easy to give full play to the advantages of biomimetic mineralization of materials.

[0030] This invention organically combines biomimetic mineralization and antibacterial functions, achieving a synergistic effect between the two. During enamel restoration, the antibacterial function effectively inhibits the growth and reproduction of oral bacteria, reducing bacterial re-erosion of newly formed enamel and providing a favorable microenvironment for stable remineralization of the enamel, thereby significantly improving the quality and durability of enamel restoration. This synergistic effect is unparalleled by traditional single-function materials, fundamentally solving the problem of enamel repair after damage and reducing the possibility of caries recurrence. It is a promising dual-material for mineralization and restoration in the treatment of early enamel caries.

[0031] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0032] Figure 1 These are SEM images of the biomimetic mineralization effect test of this invention under different soaking times; in, Figure 1 In the image, 'a' represents a SEM image taken after 1 day of soaking. Figure 1 In the image, b represents the SEM image after 3 days of soaking treatment. Figure 1 In the image, 'c' represents the SEM image after 7 days of soaking treatment. Figure 2 This is a CLSM diagram from the experiment on the inhibition of S. mutans biofilm in this invention; Figure 3 This is a diagram showing the results of the experiment on the growth inhibition of S. mutans planktonic bacteria according to the present invention; in, Figure 3 'a' in COF FPBA Experimental results after treatment with @Honokiol heterojunction nanospheres Figure 3 b in the text represents COF FPBA Experimental results after nanosphere treatment. Detailed Implementation

[0033] The present invention will be further described below with reference to the accompanying drawings and embodiments. Unless otherwise defined, the technical or scientific terms used in this invention should have the ordinary meaning understood by one of ordinary skill in the art to which this invention pertains. The features mentioned above or in the specific examples mentioned in this invention can be combined arbitrarily, and these specific embodiments are only used to illustrate the invention and are not intended to limit the scope of the invention.

[0034] Example 1 Preparation of raw materials: Dissolve 30 mg of magnolol in 1 mL of dimethyl sulfoxide to obtain a magnolol solution.

[0035] 14 mg of 1,3,5-tris(4-aminophenyl)benzene (TAPB) was dissolved in 2 mL of acetonitrile to obtain a 1,3,5-tris(4-aminophenyl)benzene solution.

[0036] 5 mg of polyvinylpyrrolidone (PVP, weight average molecular weight 360,000) was dissolved in 2 mL of acetonitrile to obtain a polyvinylpyrrolidone solution.

[0037] 12 mg of 2,5-dimethoxybenzene-1,4-dicarboxaldehyde (DMTP) was dissolved in 20 mL of methanol to obtain a 2,5-dimethoxybenzene-1,4-dicarboxaldehyde solution.

[0038] The preparation process of 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid (FPBA) includes: (1) 1.2 mmol of 2,5-dihydroxyterephthalaldehyde and 4.8 mmol of ethyl 4-bromobutyrate were dissolved in 20 mL of N,N-dimethylformamide. Then, 4.8 mmol of potassium carbonate was added to the system and the reaction was carried out at 75°C for 12 h. After the reaction was completed, the reaction system was extracted four times with dichloromethane and then purified by silica gel column chromatography using petroleum ether-ethyl acetate (volume ratio 5:1) as the eluent to obtain the precursor FPBA-CH3. (2) Dissolve 0.3 mmol of the precursor FPBA-CH3 in 30 mL of methanol solution to obtain a precursor solution, and add 10 mL of 0.24 mmol / L methanol solution to the precursor solution. L of sodium hydroxide solution, at 50 The reaction was carried out at a certain temperature for 12 hours. After the reaction was completed, the methanol solution was removed by rotary evaporation, and the mixture was cooled to 25°C. Then, a concentration of 6 mol was added to the reaction system. The pH of the reaction system was adjusted to 2.5 by adding L of hydrochloric acid solution dropwise. After a pale yellow solid precipitated, the reaction system was filtered, and the obtained solid product was washed with distilled water and dried under vacuum to obtain 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid.

[0039] A method for preparing COF heterojunction nanospheres with biomimetic mineralization and antibacterial functions includes the following preparation steps: S1. Mix the prepared magnolol solution, 1,3,5-tris(4-aminophenyl)benzene solution, polyvinylpyrrolidone solution, and 2,5-dimethoxybenzene-1,4-dicarboxaldehyde solution, then add 1 mL of acetic acid and mix to obtain COF. DMTP@Honokiol nanospheres; S2. Take 0.62 mmol of the 4,4'-((2,5-dicarboxy-1,4-phenylene)bis(oxy))dibutyric acid prepared above, and 10 mg of COF DMTP @Honokiol nanospheres, 4 mL of acetonitrile, 40 Concentration 12mol A solution of acetic acid of L was mixed and sealed in a 10 mL Shrek tube. The mixture was then incubated under vacuum at 90°C. After reacting for 72 hours, COF was obtained. FPBA @Honokiol heterojunction nanospheres.

[0040] Comparative Example 1 The preparation process is basically the same as in Example 1, except that magnolol solution is not added in S1, and the final product is denoted as COF. FPBA Nanospheres.

[0041] Testing of biomimetic mineralization effect: Take 300 COF prepared in Example 1 FPBA @Honokiol heterojunction nanospheres (dispersion), diluted in 2 mL of methanol, yielded COF. FPBA @Honokiol heterojunction nanosphere dispersion. Then take 50 COF FPBA @Honokiol heterojunction nanosphere dispersion was dropped onto the surface of acid-etched enamel sections and allowed to stand for 10 minutes. The sections were then sequentially immersed and washed in acetonitrile, methanol, and deionized water to obtain COF. FPBA @Honokiol modified acid-etched enamel substrate section; The COF obtained above FPBA @Honokiol-modified acid-etched enamel substrate sections were placed in centrifuge tubes containing 30 mL of 1.5×SBF solution (1.5 times the concentration of standard SBF solution) and centrifuged at 37°C. The COF solutions were immersed in a constant-temperature oil bath for 1, 3, and 7 days respectively. During the immersion period, the SBF solution was changed every 24 hours. After immersion, the COF was removed from the centrifuge tubes. FPBA @Honokiol-modified acid-etched enamel substrate sections were washed with deionized water and then allowed to air dry. Next, the samples were dehydrated in ascending ethanol. After dehydration, the samples were further dehydrated and dried using hexamethyldisilazane, and then dried at 25°C. Samples were air-dried under specific conditions to obtain samples with different soaking times.

[0042] The above samples were observed using a scanning electron microscope, and the results were... Figure 1 As shown. From Figure 1 It can be seen that after soaking for 1 day, a large number of parallel-arranged nanorod crystals were also generated on the surface of the acid-etched enamel substrate; as the number of soaking (mineralization) days increased, the number of regenerated crystals increased, the structure became dense and orderly, and the surface became smooth; after soaking for another 7 days, the surface of the acid-etched enamel was covered with a large number of nanorod crystals, and the fish-scale structure of the acid-etched enamel was no longer visible, and the biomimetic mineralization repair effect was obvious.

[0043] Inhibition experiments on S. mutans biomembranes: Take 300 COF prepared in Example 1 FPBA @Honokiol heterojunction nanospheres (dispersion) and COF prepared in Comparative Example 1 FPBA The nanospheres were diluted in 2 mL of methanol to obtain the corresponding dispersions.

[0044] HAp slices with a thickness of 2 mm were irradiated under ultraviolet light for 1 hour. Then, the dispersion obtained above was added dropwise to the surface of the HAp slices, allowed to stand at room temperature for 10 minutes, rinsed twice with sterile PBS, and then allowed to air dry in a ventilated area. COF was obtained separately. FPBA Processed HAp slices and COF-treated slices FPBA HAp slices processed by @Honokiol.

[0045] The overnight cultured S. mutans ATCC 251755 strain was subcultured into fresh brain heart broth (BHI) and cultured until it reached the mild exponential phase (OD600nm = 0.5). Then, it was diluted with BHI medium at a ratio of 1:100 to obtain a bacterial suspension.

[0046] Will pass through COF FPBA Processed HAp slices and COF-treated slices FPBA Honokiol-treated HAp slices and untreated HAp slices were placed in 24-well plates, and 1 mL of bacterial suspension was added. The plates were incubated at 37°C. Co-culturing was performed under constant temperature conditions and anaerobic environment for 48 hours. After culturing, the HAp sections were removed and rinsed three times with sodium chloride to remove airborne bacteria. Then, in the dark, they were incubated at 75°C. SYTO9 and PI were used to stain HAp sections for 15 minutes, followed by washing twice with PBS to remove excess dye. At this point, live bacteria showed green fluorescence, while dead bacteria showed red fluorescence.

[0047] Changes in the biofilm of *S. mutans* were observed using confocal laser scanning microscopy (CLSM), and the results are as follows: Figure 2 As shown. From Figure 2 It can be seen that after COF FPBA The S. mutans biofilm treated with nanospheres (Comparative Example 1) exhibited overall green fluorescence, indicating that the biofilm was dead. (The low percentage of live bacteria indicates that COF alone) FPBA Nanospheres have no effect on the formation of S. mutans biofilms, while those treated with COF... FPBA The *S. mutans* biofilm treated with @Honokiol heterojunction nanospheres exhibits overall red fluorescence, indicating a good antibacterial effect.

[0048] Growth inhibition experiment on S. mutans planktonic bacteria: Take 300 COF prepared in Example 1 FPBA @Honokiol heterojunction nanospheres (dispersion) and COF prepared in Comparative Example 1 FPBA The nanospheres were diluted in 2 mL of methanol to obtain the corresponding dispersions.

[0049] The overnight cultured *S. mutans* ATCC 251755 strain was inoculated into fresh BHI medium for subculturing until it reached the temperate exponential phase, at which point the OD600nm value reached 0.5. Subsequently, it was diluted 1:100 with BHI medium, and then the two dispersions prepared above were added to obtain the corresponding planar bacterial solutions.

[0050] The above-obtained planktonic bacterial solutions were added to 96-well cell culture plates. The plates were then placed at 37°C. Anaerobic culture was performed under the specified conditions, and the results were as follows: Figure 3 As shown. From Figure 3 It can be seen that COF FPBA @Honokiol heterojunction nanospheres exhibit a good inhibitory effect on the growth of S. mutans and the formation of biofilms, and have the potential to treat early dental caries.

[0051] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method for preparing COF heterojunction nanospheres with dual functions of biomimetic mineralization and antibiosis, characterized in that, The preparation method comprises the following steps: S1, mixing honokiol solution, 1,3,5-tris(4-aminophenyl)benzene solution, polyvinylpyrrolidone solution, 2,5-dimethoxybenzene-1,4-diformaldehyde solution, acetic acid to obtain COF DMTP @Honokiol nanospheres; S2, 4,4'-((2,5-diformyl-1,4-phenylene)bis(oxy))dibutanoic acid, COF DMTP @Honokiol nanospheres, acetonitrile, acetic acid solution are mixed, and reacted under vacuum conditions to obtain COF FPBA @Honokiol heterojunction nanospheres.

2. The method of claim 1, wherein the COF heterojunction nanospheres with bionic mineralization and antibacterial dual functions are prepared by the method, characterized in that, The magnolol solution in S1 comprises magnolol and dimethyl sulfoxide, and the mass-volume ratio of magnolol and dimethyl sulfoxide is 20-50 mg: 1 mL; The 1,3,5-tris(4-aminophenyl) benzene solution comprises 1,3,5-tris(4-aminophenyl) benzene and acetonitrile, and the mass-volume ratio of 1,3,5-tris(4-aminophenyl) benzene and acetonitrile is 10-15 mg: 2 mL.

3. The method for preparing COF heterojunction nanospheres with biomimetic mineralization and antibacterial dual functions according to claim 1, characterized in that, The polyvinylpyrrolidone solution in S1 comprises polyvinylpyrrolidone and acetonitrile, and the mass-volume ratio of polyvinylpyrrolidone and acetonitrile is 3-7 mg: 2 mL, and the weight average molecular weight of polyvinylpyrrolidone is 35000-38000; The 2,5-dimethoxybenzene-1,4-dicarboxaldehyde solution comprises 2,5-dimethoxybenzene-1,4-dicarboxaldehyde and methanol, and the mass-volume ratio of 2,5-dimethoxybenzene-1,4-dicarboxaldehyde and methanol is 12 mg: 15-20 mL.

4. The method for preparing COF heterojunction nanospheres with biomimetic mineralization and antibacterial dual functions according to claim 2, characterized in that, The mass-volume ratio of magnolol, 1,3,5-tris(4-aminophenyl) benzene and acetic acid is 20-50 mg: 10-15 mg: 1 mL.

5. The method for preparing COF heterojunction nanospheres with biomimetic mineralization and antibacterial dual functions according to claim 3, characterized in that, The mass-volume ratio of polyvinylpyrrolidone, 2,5-dimethoxybenzene-1,4-dicarboxaldehyde and acetic acid is 3-7 mg: 12 mg: 1 mL.

6. The method for preparing COF heterojunction nanospheres with biomimetic mineralization and antibacterial dual functions according to claim 1, characterized in that, S2 4,4'-((2,5-diformyl-1,4-phenylene)bis(oxy)) dibutanoic acid, COF DMTP @The molar mass of honokiol nanospheres is 0.62 mmol: 8-12 mg.

7. The method of claim 1, wherein the COF heterojunction nanospheres with bionic mineralization and antibacterial dual functions are prepared by the method, characterized in that, COF in S2 DMTP @The mass-volume ratio of honokiol nanospheres, acetonitrile, and acetic acid solution is 8-12 mg: 4 mL: 40 The concentration of acetic acid solution is 10-12 mol L.

8. The method for preparing COF heterojunction nanospheres with biomimetic mineralization and antibacterial dual functions according to claim 1, characterized in that, The temperature of the reaction in S2 is 80-90 , the time of the reaction is 70-74 h.

9. The biomimetic mineralization and antibacterial bifunctional COF heterojunction nanospheres prepared by the preparation method of the biomimetic mineralization and antibacterial bifunctional COF heterojunction nanospheres according to any one of claims 1-8.

10. The application of the biomimetic mineralization and antibacterial bifunctional COF heterojunction nanospheres according to claim 9 in dental enamel repair and oral antibacterial treatment.

Images