A periodontitis-targeted antibacterial supramolecular material, its preparation method and application

Abstract

This invention discloses a periodontitis-targeted antibacterial supramolecular material, its preparation method, and its application. It belongs to the field of catalyst technology. The preparation method of the periodontitis-targeted antibacterial supramolecular material includes the following steps: dissolving 2,5-dihydroxyterephthalic acid and tetrakis(4-aminophenyl)porphyrin in a first solvent, adding a first catalyst to react, and obtaining a DHA-TAPP COF skeleton; dispersing the DHA-TAPP COF skeleton in a second solvent, adding 3-bromopropyltrimethylammonium bromide and a second catalyst to react, and obtaining Q-COF; dispersing Q-COF in a third solvent, mixing it with H2PtCl6 solution, and then placing it under light conditions to obtain Pt-Q-COF; dispersing Pt-Q-COF in a buffer solution, adding pyruvate oxidase for adsorption treatment, and obtaining POx-Pt-Q-COF. This invention achieves a synergistic effect of "targeted enrichment - dual ROS generation - closed-loop H2O2 supply" through material structure design and functional unit integration, thereby improving the clearance efficiency of periodontal pathogens while ensuring biocompatibility.

Description

Technical Field

[0001] This invention relates to the field of catalyst technology, specifically to a periodontitis-targeting antibacterial supramolecular material, its preparation method, and its application. Background Technology

[0002] Periodontitis is a prevalent chronic infectious oral disease worldwide. Its core pathological mechanism involves the overgrowth of pathogenic bacteria such as *Porphyromonas gingivalis* and *Aggregobacter actinomycetes* within the periodontal pockets, leading to persistent inflammation. This inflammation gradually erodes the periodontal supporting tissues such as the gums and alveolar bone, eventually causing teeth to loosen and fall out. It can also affect overall health through blood circulation, showing a clear link to diabetes, cardiovascular disease, and premature birth. Therefore, achieving precise and long-lasting antibacterial treatment is a core need in the field of oral medicine.

[0003] Currently, the three mainstream clinical antibacterial methods and the promising covalent organic framework (COF) materials all face technical bottlenecks. Traditional chemical antibacterial methods, represented by metronidazole gel and chlorhexidine mouthwash, can kill bacteria, but their targeting is poor, with less than 5% of the drug reaching the 2-6 mm deep periodontal pocket, requiring frequent high-dose administration. Furthermore, in recent years, the resistance rate of pathogenic bacteria to these drugs has increased significantly, resulting in short-lasting efficacy and poor patient compliance. Traditional nanoparticle drug delivery systems, such as liposomes and PLGA microspheres, while attempting to improve targeting and long-term efficacy, are susceptible to destruction by the periodontal microenvironment, failing to overcome single antibacterial mechanisms, exhibiting low efficiency against resistant strains, and unable to respond to pathogenic metabolic signals. Existing reactive oxygen species (ROS) antibacterial technologies include photodynamic therapy (PDT) and enzyme catalysis. PDT is limited by periodontal pocket hypoxia, and enzyme catalysis relies on exogenous H2O2, both of which suffer from carrier-related problems. Although covalent organic frameworks (COFs) have a high specific surface area (>800 m²), they offer advantages in terms of targeting and long-term efficacy. 2 With its tunable pore size (2-5nm), excellent chemical stability (structural integrity >72h in the periodontal microenvironment), and monomer designability, COF has significant potential in the biomedical field. However, existing COFs are only at the stage of single-function integration: some only load porphyrin monomers to achieve photodynamic antibacterial activity, which is inefficient due to hypoxia; some only physically adsorb platinum nanoclusters (Pt NCs) to construct enzyme catalytic systems, which are electrically neutral on the surface and cannot target bacteria and depend on exogenous H2O2. They have not achieved the synergistic design of "targeted enrichment-ROS generation-substrate self-sufficiency" and cannot solve the three major bottlenecks of traditional technologies.

[0004] In summary, traditional chemical drugs and nano-drug delivery systems used for antibacterial treatment of periodontitis have the following problems: 1. Poor targeting: Traditional chemical drugs, nano-drug delivery systems, and existing COF materials cannot accurately accumulate on the surface of periodontal pathogens. Drugs accumulate in non-target tissues, increasing the risk of toxic side effects, and the effective concentration within the periodontal pocket is insufficient. 2. Single antibacterial mechanism: Traditional chemical drugs and nano-drug delivery systems rely on a single chemical bactericidal mechanism. Existing COFs only have single photodynamic or enzyme catalytic functions, both of which easily induce bacterial resistance and have low efficiency against drug-resistant strains. 3. Dependence on exogenous substrates / control: PDT relies on exogenous oxygen and light source, enzyme catalytic therapy relies on exogenous H2O2, and traditional nano-drug delivery systems rely on in vitro controlled release, which cannot adapt to the metabolic characteristics of the periodontal microenvironment and has insufficient long-term efficacy. 4. Insufficient carrier stability / adaptability: Traditional nanocarriers are easily damaged by the pH, proteases, and mechanical erosion of the periodontal microenvironment. Existing COFs do not integrate multifunctional synergy and cannot meet the "on-demand antibacterial" needs of chronic infections. Summary of the Invention

[0005] The purpose of this invention is to provide a periodontitis-targeted antibacterial supramolecular material, its preparation method, and its application, so as to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, embodiments of the present invention provide the following technical solution: a method for preparing a periodontitis-targeted antibacterial supramolecular material, comprising the following steps:

[0007] Skeleton synthesis: 2,5-Dihydroxyterephthalic acid and tetrakis(4-aminophenyl)porphyrin were dissolved in a first solvent, and a first catalyst was added to react and obtain the DHA-TAPP COF skeleton;

[0008] Quaternary ammonium salt modification: The DHA-TAPP COF skeleton was dispersed in a second solvent, and 3-bromopropyltrimethylammonium bromide and a second catalyst were added to react and obtain Q-COF;

[0009] Platinum nanocluster loading: Q-COF was dispersed in a third solvent and mixed with H2PtCl6 solution, and then placed under light conditions to obtain Pt-Q-COF loaded with platinum nanoclusters;

[0010] Pyruvate oxidase loading: Pt-Q-COF was dispersed in buffer solution and pyruvate oxidase was added for adsorption treatment to obtain POx-Pt-Q-COF, a periodontitis-targeted antibacterial supramolecular material.

[0011] Furthermore, the first solvent is a mixture of n-butanol and o-dichlorobenzene; the second solvent is N,N-dimethylformamide; the third solvent is deionized water; and the buffer solution is PBS buffer.

[0012] Furthermore, in the skeleton synthesis step, the reaction temperature is 120-150℃.

[0013] Furthermore, the first catalyst is glacial acetic acid; the second catalyst is potassium carbonate.

[0014] Furthermore, in the quaternary ammonium salt modification step, the mass ratio of DHA-TAPP COF to 3-bromopropyltrimethylammonium bromide is 1:(3-7), and the reaction temperature is 70-90℃.

[0015] Furthermore, in the platinum nanocluster loading step, the concentration of the H2PtCl6 solution is 3-7 mmol / L, the volume ratio of the third solvent to the H2PtCl6 solution is 1:(3-7), and the mass-volume ratio of Q-COF to the third solvent is (0.003-0.007) g:1 mL.

[0016] Furthermore, in the platinum nanocluster loading step, the illumination conditions are: irradiation under a full-spectrum white light (xenon lamp) light source.

[0017] Furthermore, in the pyruvate oxidase loading step, the mass ratio of Pt-Q-COF to pyruvate oxidase is (0.02-0.04):(3-7).

[0018] Another objective of this invention is to provide a periodontitis-targeted antibacterial supramolecular material prepared by the above-described preparation method, which includes a core carrier, a targeting unit, an enzyme catalytic unit, and a closed-loop H2O2 supply unit.

[0019] Another objective of this invention is to provide the application of the above-mentioned periodontitis-targeting antibacterial supramolecular material in the preparation of drugs for treating periodontitis.

[0020] The method for preparing periodontitis-targeted antibacterial supramolecular materials provided by this invention, through quaternary ammonium salt modification, can improve the enrichment rate of the material on the bacterial surface, significantly increase the local antibacterial concentration, significantly enhance the targeting, reduce drug exposure in non-target tissues, and reduce the risk of toxic side effects.

[0021] This invention addresses local hypoxia through a dual ROS generation pathway of "photodynamic-enzyme catalysis," significantly improving ROS generation efficiency and thereby significantly enhancing the antibacterial efficiency and drug resistance of the material.

[0022] This invention constructs a closed-loop H2O2 supply system by loading pyruvate oxidase, which can achieve H2O2 self-sufficiency, effectively control the recurrence of chronic infections, and enhance long-term antibacterial ability.

[0023] The DHA-TAPP COF backbone synthesized in this invention is composed of biocompatible elements C, H, O, and N, exhibiting excellent biocompatibility. Furthermore, the loading of Pt NCs and pyruvate oxidase is within a safe range, and co-incubation with gingival fibroblasts shows no significant cytotoxicity, meeting the requirements for clinical translation. Attached Figure Description

[0024] Figure 1 The image shows the XRD pattern of the DHA-TAPP COF skeleton obtained in Example 1.

[0025] Figure 2 The results are BET tests on the DHA-TAPP COF skeleton prepared in Example 1.

[0026] Figure 3 The image shows the zeta potential analysis results of the DHA-TAPP COF skeleton prepared in Example 1.

[0027] Figure 4 The image shows the FT-IR spectrum of the DHA-TAPP COF skeleton prepared in Example 1.

[0028] Figure 5 The image shows a TEM image of Pt-Q-COF prepared in Example 1.

[0029] Figure 6 Another TEM image of Pt-Q-COF prepared in Example 1.

[0030] Figure 7 This is a graph showing the bacterial activity test results for the control group.

[0031] Figure 8 The graph shows the bacterial activity test results for the POx-Pt-Q-COF treatment group.

[0032] Figure 9 A comparison of gingival fibroblast survival rates at different POx-Pt-Q-COF concentrations. Detailed Implementation

[0033] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0034] This invention aims to address the core bottlenecks in the antibacterial treatment of periodontitis: existing antibacterial methods lack targeting ability, requiring high-dose administration to maintain efficacy, thus increasing the risk of toxic side effects; traditional antibacterial materials have a single mechanism, easily inducing drug resistance in bacteria, leading to long-term attenuation of treatment effects; and existing solutions generally lack long-lasting antibacterial capabilities, making them unsuitable for the treatment needs of chronic persistent periodontitis infections and failing to meet clinical demands for precise and long-lasting treatment. This invention, through material structure design and functional unit integration, achieves a synergistic effect of "targeted enrichment - dual ROS generation - closed-loop H2O2 supply," improving the clearance efficiency of periodontal pathogens while ensuring biocompatibility. It solves the problems of poor targeting, single mechanism, reliance on exogenous substrates, and insufficient long-lasting effects in existing technologies, providing a new strategy for precise and long-lasting treatment of periodontitis.

[0035] Specifically, in one embodiment of the present invention, an integrated periodontitis-targeted antibacterial supramolecular material (denoted as POx-Pt-Q-COF) is constructed through stepwise modification and functional unit loading, comprising a core carrier, a targeting unit, an enzyme catalytic unit, and a closed-loop H2O2 supply unit. The preparation method includes the following steps:

[0036] S1. Synthesis of the core carrier DHA-TAPP COF framework: 2,5-Dihydroxyterephthalic acid (DHA) was used as the hydroxyl-containing monomer, and tetrakis(4-aminophenyl)porphyrin (TAPP) was used as the porphyrin-containing monomer. The two monomers were dissolved in 10 mL of a first solvent at a 1:1 molar ratio. 0.05-0.15 mL of glacial acetic acid catalyst was added, and the reaction was carried out at 120-150℃ to obtain a crystalline DHA-TAPP COF framework. The first solvent was a mixed solvent of n-butanol and o-dichlorobenzene. The pore size of this DHA-TAPP COF framework was 2-5 nm, and the specific surface area was ≥800 m². 2 / g, TAPP endows it with broad-spectrum / visible light photoresponse characteristics, providing a basis for photodynamic antibacterial and Pt NCs photoreduction.

[0037] S2. Quaternary ammonium salt modification to construct targeted modification units: 0.1 g of DHA-TAPP COF backbone was dispersed in 20 mL of a second solvent, and 0.3-0.7 g of 3-bromopropyltrimethylammonium bromide and potassium carbonate catalyst were added. The reaction was carried out at 70-90 °C to obtain Q-COF; the second solvent was DMF; the surface zeta potential of Q-COF was +20~+30 mV, and it could target and bind to negatively charged bacterial cell membranes through electrostatic interaction.

[0038] S3. Platinum nanoclusters (Pt NCs) supported to construct an enzyme-catalyzed antibacterial unit: 0.03-0.07 mg of Q-COF was dispersed in 10 mL of a third solvent and mixed with 3-7 mL of H2PtCl6 solution with a concentration of 3-7 mmol / L. The mixture was then placed under a full-spectrum white light source (xenon lamp) with a power density of 80-120 mW / cm². 2 Pt-Q-COF loaded with platinum nanoclusters was obtained by irradiation for 2-4 hours under the following conditions: the third solvent was deionized water; Pt NCs have peroxidase-like activity and can catalyze the generation of oxygen from H2O2.

[0039] S4. Pyruvate oxidase loading to construct a closed-loop H2O2 supply unit: 0.02-0.04 g of Pt-Q-COF was dispersed in 5 mL of PBS buffer, and 3-7 mg of pyruvate oxidase was added. Adsorption was performed at 3-5 °C to obtain the periodontitis-targeted antibacterial supramolecular material POx-Pt-Q-COF. Pyruvate oxidase can catalyze the conversion of pyruvate, a metabolic product of pathogenic bacteria, into H2O2, achieving substrate self-sufficiency.

[0040] The working process of the periodontitis-targeted antibacterial supramolecular material POx-Pt-Q-COF prepared above is as follows:

[0041] 1. Targeted enrichment stage: The positively charged quaternary ammonium salt groups on the surface of POx-Pt-Q-COF interact electrostatically with the negatively charged bacterial cell membrane, resulting in precise enrichment on the surface of periodontal pathogens and increasing the local antibacterial concentration.

[0042] 2. Dual ROS generation stage: Under full-spectrum white light irradiation, TAPP photoresponse produces ROS (photodynamic pathway); at the same time, Pt NCs catalyze H2O2 to generate oxygen (enzymatic pathway), achieving oxygen self-sufficiency. The two work synergistically to enhance ROS generation efficiency.

[0043] 3. Closed-loop H2O2 supply stage: Pyruvate produced by pathogenic bacteria metabolism is catalyzed by pyruvate oxidase to generate H2O2, which continuously supplies energy to the Pt NCs enzyme catalytic pathway, forming a closed loop of "bacterial metabolism → H2O2 → Pt NCs activation → ROS sterilization", ensuring the continuity of antibacterial activity.

[0044] In this embodiment of the invention, DHA and TAPP are selected as monomers, and a COF with photoresponsive properties, high specific surface area, and stable structure is constructed by a solvothermal method, providing an ideal carrier for multifunctional unit loading. Furthermore, this embodiment of the invention modifies the COF surface with 3-bromopropyltrimethylammonium bromide to make it positively charged (zeta potential +20~+30mV), achieving electrostatic targeting and binding to negatively charged bacterial cell membranes, thus solving the problem of poor targeting. This embodiment of the invention also integrates TAPP photoresponsive ROS production with Pt NCs-like peroxidase-catalyzed oxygen production, synergistically improving ROS efficiency and avoiding single-mechanism drug resistance. This embodiment of the invention loads pyruvate oxidase, utilizing the pathogenic bacterial metabolite pyruvate to generate H2O2, achieving substrate self-sufficiency, solving the problem of exogenous H2O2 dependence, and ensuring long-term antibacterial effect.

[0045] Example 1: This example provides a periodontitis-targeted antibacterial supramolecular material, the preparation method of which includes the following steps:

[0046] S1. Synthesis of the core carrier DHA-TAPP COF framework: 0.1 mmol of DHA and 0.1 mmol of TAPP were dissolved in 10 mL of a mixed solvent of n-butanol and o-dichlorobenzene (volume ratio 1:1). 0.1 mL of glacial acetic acid catalyst was added, and the mixture was sonicated for 10 min before being transferred to a 25 mL polytetrafluoroethylene reactor. The reactor was heated to 130 °C and reacted for 60 h. After the reaction, the mixture was cooled to room temperature, centrifuged at 8000 rpm for 10 min to collect the precipitate, washed three times each with DMF and ethanol, and then subjected to continuous Soxhlet extraction at 90 °C for 24 h using tetrahydrofuran (THF) as the solvent, ensuring at least 20 solvent cycles. The precipitate was then vacuum dried at 60 °C for 12 h to obtain a brownish-black crystalline DHA-TAPP COF framework.

[0047] S2. Quaternary ammonium salt modification to construct targeted modification units: 0.1 g of DHA-TAPP COF skeleton was dispersed in 20 mL of DMF, 0.5 g of 3-bromopropyltrimethylammonium bromide was added, and 20 mg of potassium carbonate was added as an alkaline catalyst. The reaction was stirred at 80 °C for 18 h, and the product was collected by centrifugation (10000 rpm, 15 min). The product was washed three times with ethanol and dried under vacuum at 60 °C for 8 h to obtain Q-COF.

[0048] S3 and Pt NCs loading were used to construct an enzyme-catalyzed antibacterial unit: 0.05 mg of Q-COF was dispersed in 10 mL of deionized water and mixed with 5 mL of 0.5 mmol / L H2PtCl6 solution. After stirring evenly, a full-spectrum white xenon lamp light source (power density of 100 mW / cm²) was used. 2Irradiate for 3 hours with continuous nitrogen protection; then centrifuge (8000 rpm, 10 min) to collect the product, wash three times with deionized water, and vacuum dry at 40℃ for 6 hours to obtain Pt-Q-COF loaded with platinum nanoclusters.

[0049] S4. Pyruvate oxidase loading to construct a closed-loop H2O2 supply unit: 0.03 g of Pt-Q-COF was dispersed in 5 mL of PBS buffer (pH=7.4), and 1 mL of PBS buffer containing 0.5 mg of pyruvate oxidase was added. The mixture was stirred and adsorbed at 4 °C for 10 h. The product was collected by centrifugation (10000 rpm, 15 min), washed twice with PBS, and vacuum dried at 4 °C for 4 h to obtain the periodontitis-targeted antibacterial supramolecular material POx-Pt-Q-COF.

[0050] Example 2: This example provides a periodontitis-targeted antibacterial supramolecular material, the preparation method of which includes the following steps:

[0051] S1. Synthesis of the core carrier DHA-TAPP COF framework: 0.1 mmol of DHA and 0.1 mmol of TAPP were dissolved in 10 mL of a mixed solvent of n-butanol and o-dichlorobenzene (volume ratio 1:1), and 0.05 mL of glacial acetic acid catalyst was added. After sonication for 10 min, the mixture was transferred to a 25 mL polytetrafluoroethylene reactor and heated to 120 °C for 72 h. After the reaction, the mixture was cooled to room temperature, centrifuged at 10,000 rpm to collect the precipitate, washed three times each with DMF and ethanol, and continuously Soxhlet extracted at 90 °C for 24 h using THF as solvent, ensuring that the solvent was circulated at least 20 times. Then, the mixture was vacuum dried at 60 °C for 12 h to obtain the crystalline DHA-TAPP COF framework.

[0052] S2. Quaternary ammonium salt modification to construct targeted modification units: 0.1 g of DHA-TAPP COF skeleton was dispersed in 20 mL of DMF, 0.3 g of 3-bromopropyltrimethylammonium bromide was added, and 20 mg of potassium carbonate was added as an alkaline catalyst. The reaction was stirred at 70 °C for 24 h, and the product was collected by centrifugation (10000 rpm, 15 min). The product was washed three times with ethanol and dried under vacuum at 60 °C for 8 h to obtain Q-COF.

[0053] S3 and Pt NCs loading were used to construct an enzyme-catalyzed antibacterial unit: 0.03 mg of Q-COF was dispersed in 10 mL of deionized water and mixed with 3 mL of 0.3 mmol / L H2PtCl6 solution. After stirring evenly, a full-spectrum white xenon lamp light source (power density of 100 mW / cm²) was used. 2Irradiate for 4 hours with continuous nitrogen protection; then centrifuge (8000 rpm, 10 min) to collect the product, wash three times with deionized water, and vacuum dry at 40℃ for 6 hours to obtain Pt-Q-COF loaded with platinum nanoclusters.

[0054] S4. Pyruvate oxidase loading to construct a closed-loop H2O2 supply unit: 0.02 g of Pt-Q-COF was dispersed in 5 mL of PBS buffer (pH=7.4), and 1 mL of PBS buffer containing 0.3 mg of pyruvate oxidase was added. The mixture was stirred and adsorbed at 3 °C for 8 h to allow physical adsorption of the enzyme and COF. The product was collected by centrifugation (10000 rpm, 15 min), washed twice with PBS, and vacuum dried at 4 °C for 4 h to obtain the periodontitis-targeted antibacterial supramolecular material POx-Pt-Q-COF.

[0055] Example 3: This example provides a periodontitis-targeted antibacterial supramolecular material, the preparation method of which includes the following steps:

[0056] S1. Synthesis of the core carrier DHA-TAPP COF framework: 0.1 mmol of DHA and 0.1 mmol of TAPP were dissolved in 10 mL of a mixed solvent of n-butanol and o-dichlorobenzene (volume ratio 1:1), and 0.15 mL of glacial acetic acid catalyst was added. After sonication for 10 min, the mixture was transferred to a 25 mL polytetrafluoroethylene reactor and heated to 150 °C for 48 h. After the reaction, the mixture was cooled to room temperature, centrifuged at 9000 rpm to collect the precipitate, washed three times each with DMF and ethanol, and then continuously Soxhlet extracted at 90 °C under reflux for 24 h using THF as solvent, ensuring that the solvent was circulated at least 20 times. Finally, the mixture was vacuum dried at 60 °C for 12 h to obtain the crystalline DHA-TAPP COF framework.

[0057] S2. Quaternary ammonium salt modification to construct targeted modification units: 0.1 g of DHA-TAPP COF skeleton was dispersed in 20 mL of DMF, 0.7 g of 3-bromopropyltrimethylammonium bromide was added, and 20 mg of potassium carbonate was added as an alkaline catalyst. The reaction was stirred at 90 °C for 12 h, and the product was collected by centrifugation (10000 rpm, 15 min). The product was washed three times with ethanol and dried under vacuum at 60 °C for 8 h to obtain Q-COF.

[0058] S3 and Pt NCs loading were used to construct an enzyme-catalyzed antibacterial unit: 0.07 mg of Q-COF was dispersed in 10 mL of deionized water and mixed with 7 mL of 0.7 mmol / L H2PtCl6 solution. After stirring evenly, a full-spectrum white xenon lamp light source (power density of 100 mW / cm²) was used. 2Irradiate for 2 hours with continuous nitrogen protection; then centrifuge (8000 rpm, 10 min) to collect the product, wash three times with deionized water, and vacuum dry at 40℃ for 6 hours to obtain Pt-Q-COF loaded with platinum nanoclusters.

[0059] S4. Pyruvate oxidase loading to construct a closed-loop H2O2 supply unit: 0.04 g of Pt-Q-COF was dispersed in 5 mL of PBS buffer (pH=7.4), and 1 mL of PBS buffer containing 0.7 mg of pyruvate oxidase was added. The mixture was stirred and adsorbed at 5 °C for 12 h to allow physical adsorption of the enzyme and COF. The product was collected by centrifugation (10000 rpm, 15 min), washed twice with PBS, and vacuum dried at 4 °C for 4 h to obtain the periodontitis-targeted antibacterial supramolecular material POx-Pt-Q-COF.

[0060] Structural Characterization and Performance Testing: I. The DHA-TAPP COF skeleton obtained in Example 1 was characterized by XRD and subjected to BET testing. The results are as follows: Figure 1 and Figure 2 As shown in the figure, XRD characterization reveals characteristic diffraction peaks (2θ = 4.8°), indicating a complete crystalline structure. The peak shape variation reflects the high crystallinity of the synthesized original COF material. BET testing results show a specific surface area of ​​906 m². 2 / g, with pore sizes concentrated at 2.7nm, enabling efficient loading of subsequent functional units.

[0061] II. The DHA-TAPP COF framework and Q-COF prepared in Example 1 were subjected to zeta potential analysis and FT-IR spectral characterization. The results are as follows: Figure 3 and Figure 4 As shown in the figure, Zeta potential analysis reveals that the surface charge changes from negative to positive (from -13 mV to +20.2 mV), confirming the successful introduction of the quaternary ammonium salt cation. FT-IR spectroscopy shows the C=N double bond (~1620-1650 cm⁻¹). -1 The characteristic peaks remained unchanged, proving that the COF framework was perfectly preserved; ~1480cm -1 -CH2-N + - The appearance of characteristic peaks, and the methyl (-CH3) bending vibration peak (1370~1400cm). -1 This further demonstrates the existence of quaternary ammonium salt groups (-N). + (CH3)3) Stable load on the material surface.

[0062] III. The Pt-Q-COF prepared in Example 1 was characterized by TEM at different magnifications, and the results are as follows: Figure 5 and Figure 6As shown in the figure, Pt NCs in Pt-Q-COF are uniformly distributed with a size of approximately 2.1 nm.

[0063] IV. Antibacterial Properties: To evaluate the disruptive effect of POx-Pt-Q-COF prepared in Example 1 on the biofilm of *Porphyromonas gingivalis* (P. gingivalis), standard strains of *P. gingivalis* were cultured to the logarithmic growth phase and then anaerobic at 37°C for 96 hours to form mature biofilms. POx-Pt-Q-COF solution (final concentration 200 μg / mL) was then added to each well, followed by irradiation with a 660 nm laser for 10 minutes. Finally, bacterial activity was assessed using the colony-forming unit (CFU) counting method: the CFU values ​​of the POx-Pt-Q-COF treatment group (with POx-Pt-Q-COF) and the control group (without POx-Pt-Q-COF) were compared to quantify the disruptive effect of this combined treatment on the *P. gingivalis* biofilm. The results are as follows: Figure 7 and Figure 8 As shown in the figure. The final results show that, compared with the control group, the POx-Pt-Q-COF treatment group had a CFU reduction of approximately 4 log, demonstrating a significant effect on biofilm disruption.

[0064] Biocompatibility: Gingival fibroblast viability was tested by treating POx-Pt-Q-COF solutions of different concentrations with or without light exposure. The results are as follows: Figure 9 As shown in the figure, at concentrations of 25-400 μg / mL, with or without light exposure, the survival rate of gingival fibroblasts was greater than 80%, demonstrating excellent biocompatibility.

[0065] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification.

Claims

1. A periodontitis-targeted antibacterial supramolecular material, characterized in that, The preparation method of the periodontitis-targeted antibacterial supramolecular material includes a core carrier, a targeted modification unit, an enzyme-catalyzed antibacterial unit, and a closed-loop H2O2 supply unit; the method includes the following steps: Synthesis of the core carrier skeleton: 2,5-dihydroxyterephthalic acid and tetrakis(4-aminophenyl)porphyrin were dissolved in the first solvent, and the first catalyst was added to carry out the reaction to obtain the DHA-TAPP COF skeleton; Quaternary ammonium salt modification to construct targeted modification units: The DHA-TAPP COF skeleton was dispersed in a second solvent, and 3-bromopropyltrimethylammonium bromide and a second catalyst were added to react and obtain Q-COF; Platinum nanoclusters loaded to construct enzyme-catalyzed antibacterial units: Q-COF was dispersed in a third solvent and mixed with H2PtCl6 solution, and then placed under light conditions to obtain Pt-Q-COF loaded with platinum nanoclusters; Pyruvate oxidase loading to construct a closed-loop H2O2 supply unit: Pt-Q-COF was dispersed in a buffer solution and pyruvate oxidase was added for adsorption treatment to obtain the periodontitis-targeted antibacterial supramolecular material POx-Pt-Q-COF.

2. The periodontitis-targeted antibacterial supramolecular material according to claim 1, characterized in that, The first solvent is a mixture of n-butanol and o-dichlorobenzene; the second solvent is N,N-dimethylformamide; the third solvent is deionized water; and the buffer solution is PBS buffer.

3. The periodontitis-targeted antibacterial supramolecular material according to claim 1, characterized in that, In the skeleton synthesis step, the reaction temperature is 120-150℃.

4. The periodontitis-targeted antibacterial supramolecular material according to claim 1, characterized in that, The first catalyst is glacial acetic acid; the second catalyst is potassium carbonate.

5. The periodontitis-targeted antibacterial supramolecular material according to claim 1, characterized in that, In the quaternary ammonium salt modification step, the mass ratio of DHA-TAPP COF to 3-bromopropyltrimethylammonium bromide is 1:(3-7), and the reaction temperature is 70-90℃.

6. The periodontitis-targeted antibacterial supramolecular material according to claim 1, characterized in that, In the platinum nanocluster loading step, the concentration of the H2PtCl6 solution is 3-7 mmol / L, the volume ratio of the third solvent to the H2PtCl6 solution is 1:(3-7), and the mass-volume ratio of Q-COF to the third solvent is (0.003-0.007) g:1 mL.

7. The periodontitis-targeted antibacterial supramolecular material according to claim 1 or 6, characterized in that, In the platinum nanocluster loading step, the illumination conditions are: irradiation under a full-spectrum white xenon lamp light source.

8. The periodontitis-targeted antibacterial supramolecular material according to claim 1, characterized in that, In the pyruvate oxidase loading step, the mass ratio of Pt-Q-COF to pyruvate oxidase is (0.02-0.04):(3-7).

9. The use of a periodontitis-targeting antibacterial supramolecular material as described in any one of claims 1-8 in the preparation of a drug for treating periodontitis.

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