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CN-121987823-A - ZIF-8-EGCG/Co2+Preparation method and application of @ ZnPc nanocomposite

CN121987823ACN 121987823 ACN121987823 ACN 121987823ACN-121987823-A

Abstract

The invention discloses a preparation method and application of a ZIF-8-EGCG/Co 2+ @ZnPc nanocomposite. The composite material further integrates the EB virus targeting recognition capability and antibacterial activity of EGCG, fenton-like catalytic property of Co 2+ and photodynamic effect of ZnPc on the basis of guaranteeing remarkable surface area characteristics, adjustable pore canal structures and excellent biocompatibility by taking ZIF-8 metal organic framework as a main body, realizes directional enrichment and controllable release of drugs at tumor sites through an acid response trigger mechanism, generates synergetic enhanced ROS, effectively induces death of tumor cells, and simultaneously inhibits microbial colonization closely related to nasopharyngeal carcinoma occurrence and development, thereby providing an innovative solution for overcoming clinical challenges that traditional operations are difficult to eradicate tiny foci, normal tissue injury is easy to cause and the like.

Inventors

  • CHEN JUANJUAN
  • Dai Linpeng

Assignees

  • 福州大学

Dates

Publication Date
20260508
Application Date
20260211

Claims (10)

  1. 1. A preparation method of a ZIF-8-EGCG/Co 2+ @ZnPc nanocomposite is characterized by comprising the following steps: (1) Uniformly mixing zinc nitrate hexahydrate and 2-methylimidazole in methanol, standing for 12-48 hours at room temperature, centrifuging, washing and vacuum drying the obtained precipitate to obtain ZIF-8 solid; (2) Grinding the ZIF-8 solid obtained in the step (1), mixing with epigallocatechin gallate, adding a sodium phosphate buffer solution, stirring for 1-3 h, centrifuging, washing and drying the precipitate to obtain a product ZE; (3) Mixing the ZE product obtained in the step (2) with CoCl 2 and absolute ethyl alcohol, stirring under a constant-temperature water bath, centrifuging, washing and drying the obtained product after the reaction is finished to obtain a product ZEC; (4) And mixing the ZEC absolute ethanol solution with the ZnPc DMF solution, stirring and reacting for 2-6 h under the dark condition, centrifuging and washing the precipitate obtained after the reaction is finished to obtain the ZIF-8-EGCG/Co 2+ @ZnPc nanocomposite.
  2. 2. The preparation method according to claim 1, wherein the molar ratio of zinc nitrate hexahydrate to 2-methylimidazole in the step (1) is 1:9, the amount of methanol is 50-100 mL, the rotational speed of centrifugation is 10000-15000 rpm, and the time is 10-15 min.
  3. 3. The preparation method of claim 1, wherein in the step (2), the molar ratio of ZIF-8 solid to epigallocatechin gallate is 2:1, the amount of sodium phosphate buffer solution is 10-30 mL, the rotational speed of centrifugation is 5000-10000 rpm, and the time is 10-15 min.
  4. 4. The method of claim 1, wherein the mass ratio of ZE to CoCl 2 in the step (3) is (12.5-20 mg) (2.5-7.5 mg), the temperature of the constant-temperature water bath is 20-50 ℃, the rotational speed of centrifugation is 8000-12000 rpm, and the time is 10-20 min.
  5. 5. The preparation method according to claim 1, wherein the concentration of the anhydrous ethanol solution of ZEC in the step (4) is 1.0-2.0 mg/mL, the concentration of the DMF solution of ZnPc is 2-5 mg/mL, the dosage ratio of the two is (10-20 mL): 1-3 mL), the light-shielding stirring time range is 12-36 h, the rotational speed of centrifugation is 12000-16000 rpm, and the time range is 10-20 min.
  6. 6. A ZIF-8-EGCG/Co 2+ @ ZnPc nanocomposite prepared by the method of any one of claims 1 to 5.
  7. 7. The ZIF-8-EGCG/Co 2+ @ZnPc nanocomposite material according to claim 6, wherein the release rate of the nanocomposite material is more than 70% at pH 5-6.5, and the nanocomposite material also has antibacterial property.
  8. 8. The use of the ZIF-8-EGCG/Co 2+ @ ZnPc nanocomposite material according to any one of claims 6 or 7 in the manufacture of a medicament for the treatment of epstein barr virus-related malignancies.
  9. 9. The method according to claim 8, wherein the tumor is nasopharyngeal carcinoma, gastric cancer or lymphoma.
  10. 10. The method of claim 8, wherein the nanocomposite is a combination of photodynamic therapy and chemodynamic therapy.

Description

Preparation method and application of ZIF-8-EGCG/Co 2+ @ZnPc nanocomposite Technical Field The invention relates to the technical field of targeted tumor treatment, in particular to a preparation method and application of a ZIF-8-EGCG/Co 2+ @ZnPc nanocomposite. Background Among many tumor diseases, nasopharyngeal carcinoma has unique clinical biological characteristics, and the tumor growth position is extremely hidden and is close to human critical tissues such as brain stem, skull base bone and the like, so that the difficulty of completely resecting the tumor through operation is extremely high. At present, a comprehensive treatment means taking radiotherapy as a dominant mode becomes a main mode of nasopharyngeal carcinoma treatment. However, 20% of patients have local recurrence and distant metastasis after treatment, become refractory nasopharyngeal carcinoma groups, and have the problems of easy drug resistance initiation, high proportion of toxic and side effects, and the like, so that thorough cure cannot be realized. In addition, there is a close association between nasopharyngeal carcinoma and Epstein Barr Virus (EBV). In high-incidence areas, up to 95% of cancer tissues of patients with nasopharyngeal carcinoma can detect the integrated latent infection of EBV, which is a key pathogenic factor for the occurrence and development of nasopharyngeal carcinoma, and various products produced by the codes, especially key molecules such as latent membrane protein 1 (LMP 1), play a core role in the progress of nasopharyngeal carcinoma. Meanwhile, the related studies have further found that part of microorganisms in the oral cavity, such as Fusobacterium nucleatum and Proteus intermedia, etc., exhibit significant correlation with the EBV viral load of the nasopharynx. The microorganisms can migrate and ectopic to be planted in the nasopharynx so as to infiltrate tumor tissues, remodel the local microenvironment of the nasopharyngeal carcinoma, inhibit the anti-tumor immunity of the human body, and further increase the treatment difficulty of the nasopharyngeal carcinoma. However, the current main method for eliminating germs inside tumors depends on the systemic application of antibiotics, but the treatment mode may cause a series of side effects, such as unbalance of intestinal probiotics, generation of bacterial drug resistance, increased disease susceptibility, weakening of the effects of immunotherapy and chemotherapy, and the like. Dynamic therapy (DYNAMIC THERAPY, DT) is taken as an innovative treatment mode, and brings new hopes for accurate treatment of tumors by virtue of the dynamic treatment process that external energy (such as light, ultrasound, chemistry and the like) is relied on to trigger the tumor microenvironment to react. Among them, photodynamic therapy (PDT) has outstanding advantages in terms of anti-nasopharyngeal carcinoma as a novel therapeutic method different from the conventional therapeutic mechanism, namely, high efficiency and safety. By accurately controlling the external light source, the photosensitizer can be accurately excited in time and space, and the targeting design is combined, so that the treatment accuracy is greatly improved, the tumor can be effectively treated, the damage to normal tissues is effectively reduced, and the toxic and side effects and the drug resistance are low. The drug has extremely low systemic toxic and side effects, can not influence the drug effect and can not increase the toxic and side effects after multiple drug administration, the low drug resistance makes the drug become an ideal choice for repeated treatment, and the drug provides possibility for long-term safe treatment of nasopharyngeal carcinoma patients, and has antibacterial effect. Active oxygen substances generated after the photosensitizer is excited can not only kill tumor cells with high efficiency, but also kill surrounding pathogens, and can not cause bacterial drug resistance, and can effectively resist ectopic and fixed-planting bacteria in nasopharyngeal carcinoma, thereby being expected to promote the overall treatment effect. Unlike photodynamic therapy, which directly introduces an external light source, chemotherapy (CDT) ingeniously utilizes chemical energy in vivo, and triggers a Fenton/Fenton-like reaction by introducing specific metal ions (such as Fe 2+、Cu2+、Mn2+、Co2+, etc.), so that excessive hydrogen peroxide (H 2O2) in tumor tissues is converted into highly toxic hydroxyl radicals (OH), lipid peroxidation is induced, and tumor cells are directly damaged. Meanwhile, a great deal of researches report that a combined treatment strategy of photodynamic therapy and chemo-dynamic therapy shows good synergistic effect, and realizes a 'cooperative win-win' treatment mode. The combination of the two can generate a large amount of active oxygen substances, greatly promote the death of immunogenic cells and improve the anti-tumor immune effect. However, the combined t