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CN-122005488-A - ZIF-8-based intelligent nano bionic drug delivery system, preparation method and application

CN122005488ACN 122005488 ACN122005488 ACN 122005488ACN-122005488-A

Abstract

The invention belongs to the technical field of tumor medicaments, and in particular relates to an intelligent nano bionic medicament delivery system based on ZIF-8, a preparation method and application thereof, wherein doxorubicin, DNAzyme and an aptamer are loaded on the ZIF-8, and the preparation method comprises the following steps: after doxorubicin is loaded on a ZIF-8 nano-carrier, DNAzyme is further adsorbed by utilizing electrostatic interaction, then surface modification is carried out on an erythrocyte membrane, and finally an aptamer medicament is inserted into the surface of the cell membrane by a lipid insertion method, so that the DOX/dz@ZIF-8-RM/Apt nano-medicament delivery system is prepared, and the ZIF-8-based intelligent nano-bionic medicament delivery system is used for relieving chemotherapy resistance and improving the anti-tumor immunity efficiency so as to furthest improve the effect of the medicament in tumors.

Inventors

  • LI DAXIU
  • HE TINGTING
  • XIE JING
  • TANG YAQIN
  • HE XIAO
  • WANG YANNI

Assignees

  • 重庆理工大学

Dates

Publication Date
20260512
Application Date
20260107

Claims (7)

  1. 1. A ZIF-8-based intelligent nano bionic drug delivery system is characterized by comprising the step of loading doxorubicin, DNAzyme and an aptamer on the ZIF-8.
  2. 2. A preparation method of an intelligent nano bionic drug delivery system based on ZIF-8 is characterized in that after doxorubicin is loaded on a ZIF-8 nano carrier, DNAzyme is further adsorbed by utilizing electrostatic interaction, then surface modification is carried out on an erythrocyte membrane, and finally an aptamer drug is inserted into the surface of the cell membrane through a lipid insertion method, so that the D/Dz@Z-RM/A nano drug delivery system is prepared.
  3. 3. The method for preparing the ZIF-8-based intelligent nano bionic drug delivery system according to claim 2, wherein the method for loading the doxorubicin into the ZIF-8 nano carrier comprises the steps of adding the doxorubicin into a 2-methylimidazole solution at room temperature, stirring the solution by 1200rpm for 5min, then dropwise adding a zinc nitrate hexahydrate solution, stirring the solution at room temperature to obtain a red suspension, centrifuging the red suspension to obtain a red precipitate, and finally washing the red precipitate with water for 3 times to obtain D@Z.
  4. 4. The method for preparing the ZIF-8-based intelligent nano bionic drug delivery system according to claim 3, wherein the method for adsorbing DNAzyme by using the ZIF-8 nano carrier loaded with the doxorubicin comprises the steps of adding DNAzyme into D@Z, stirring at 37 ℃ for 30 min, centrifuging at 10000rpm for 10min, collecting precipitate, and redispersing the precipitate in deionized water to obtain D/Dz@Z.
  5. 5. The method for preparing the ZIF-8-based intelligent nano bionic drug delivery system according to claim 4, wherein the method for surface modification of the erythrocyte membrane comprises the steps of mixing D/Dz@Z with the erythrocyte membrane according to a mass ratio of 1:5, performing ultrasonic treatment, and sequentially extruding the mixture through polycarbonate membranes of 400 nm and 200 nm for 10 times to prepare the D/Dz@Z-RM.
  6. 6. The method for preparing the ZIF-8-based intelligent nano bionic drug delivery system according to claim 5, wherein the method for inserting the aptamer drug into the surface of the cell membrane comprises the steps of mixing the pH-Apt and the D/Dz@Z-RM in equal molar amounts by vortex, and incubating the mixture at 37 ℃ for 40 min to obtain the D/Dz@Z-RM/A.
  7. 7. The use of the ZIF-8-based intelligent nano-biomimetic drug delivery system according to claim 1 or the ZIF-8-based intelligent nano-biomimetic drug delivery system according to any one of claims 2-6 in the preparation of oncologic drugs.

Description

ZIF-8-based intelligent nano bionic drug delivery system, preparation method and application Technical Field The invention belongs to the technical field of tumor medicaments, and particularly relates to an intelligent nano bionic medicament delivery system based on ZIF-8, a preparation method and application thereof. Background Immunotherapy is a novel method of tumor treatment following surgery, radiation therapy, chemotherapy, in which tumor cells are controlled and destroyed by activating or enhancing immune response, thereby enhancing or normalizing the immune system of the human body. Cancer immunotherapy has changed the treatment modes of various solid tumors and hematological malignancies, bringing benefits to cancer patients, especially for advanced malignant tumor patients and multi-drug resistant cancer patients, thoroughly revolutionizing cancer treatment. Currently, chimeric antigen receptor T cell immunotherapy and Immune Checkpoint Blockade (ICB) are the most clinically effective tumor immunotherapy. In recent years, more and more cancer patients benefit from ICB therapy. ICB has shown significant promise in the clinical treatment of a variety of cancers, acting through immune responses that repair defects. Chen Liping et al found a novel immune checkpoint, siglec-15 (sialic acid binding immunoglobulin-like lectin-15), which inhibits antigen-specific T cell responses. The checkpoint can directly reverse T cell inhibition for immunotherapy. However, the overall response rate is still below the ideal level due to the high heterogeneity of tumors and redundancy of immune escape mechanisms. Furthermore, strong clinical evidence suggests that patients with poor response to ICB treatment are closely related to inadequate T cell infiltration and low immunogenicity. Induction of Immunogenic Cell Death (ICD) of tumor cells is an effective tumor treatment that can enhance the efficacy of immune checkpoint blockade therapies by remodelling the immunosuppressive tumor microenvironment, making it possible to combine immunotherapy with many ICD induction modalities such as chemotherapy. The chemotherapeutic drug Doxorubicin (DOX) is a potent ICD inducer, promoting tumor cell death and release of risk-related molecular patterns (DAMPs) and tumor-related antigens (TAAs), leading to in situ activation of anti-tumor immunity. However, systemic administration of chemotherapeutic agents can cause strong toxic side effects and drug resistance. Therefore, in order to effectively treat tumors, it is important to reduce the multidrug resistance of chemotherapeutic drugs. DNAzyme has great potential in reversing drug resistance due to the advantages of high specificity, high catalytic efficiency, good stability, low immunogenicity and the like. However, gene pharmaceuticals are limited by poor stability and retention in tumor microenvironments. Therefore, a nano bionic drug delivery system based on ZIF-8 is developed, chemotherapeutic drugs, gene therapy drugs and ICB drugs are packaged in ZIF-8 and named as D/Dz@Z-RM/A, and the nano bionic drug delivery system is used for relieving chemotherapy drug resistance and improving the efficiency of anti-tumor immunotherapy so as to furthest improve the therapeutic effect of the intratumoral therapeutic drugs. Disclosure of Invention In order to solve the problems in the prior art, the invention provides an intelligent nano bionic drug delivery system based on ZIF-8, a preparation method and application thereof, which achieve the purposes of relieving chemotherapy drug resistance and improving anti-tumor immunity efficiency so as to furthest improve the effect of the medicine in tumors. The invention solves the technical problems by adopting the following technical scheme: the invention aims to provide an intelligent nano bionic drug delivery system based on ZIF-8, which comprises the step of loading doxorubicin, DNAzyme and an aptamer on the ZIF-8. A preparation method of an intelligent nano bionic drug delivery system based on ZIF-8 comprises the steps of loading doxorubicin into a ZIF-8 nano carrier, utilizing electrostatic interaction to further adsorb DNAzyme, then carrying out surface modification by using an erythrocyte membrane, and finally inserting an aptamer drug on the surface of the cell membrane by a lipid insertion method to prepare the DOX/Dz@ZIF-8-RM/Apt (D/Dz@Z-RM/A) nano drug delivery system. Further, the method for loading the doxorubicin into the ZIF-8 nano-carrier comprises the steps of adding the doxorubicin into a 2-methylimidazole solution at room temperature, stirring the solution at 1300 rpm for 5: 5min, then dropwise adding a zinc nitrate hexahydrate solution, stirring the solution at room temperature to obtain a red suspension, centrifuging the red suspension to obtain a red precipitate, and finally washing the red precipitate with water for 3 times to obtain DOX@ZIF-8 (D@Z). Further, the method for adsorbing DNAzyme by using the doxorubicin-loa