CN-121987821-A - Preparation method and application of composite nano system based on ZIF-8 material-entrapped plant vesicles

Abstract

The invention provides a preparation method and application of a composite nano system based on ZIF-8 material-entrapped plant vesicles, and relates to the technical fields of nano material construction and biomedical engineering. The preparation method of the composite nano system based on the ZIF-8 material-entrapped plant vesicles comprises the following steps of incubating 0.07-0.10 mol/L zinc ion solution and 10 9 ~10 11 /mL plant nano vesicle solution to obtain zinc ion-PDVLNs mixed solution, mixing and reacting the zinc ion-PDVLNs mixed solution with 1-3 mol/L2-methylimidazole solution, and centrifugally collecting precipitate. The invention combines plant-derived nano vesicles with a metal organic framework, constructs a composite nano system with strong stability, centralized particle size distribution and complete structure, can respond and release in an acidic tumor microenvironment, and has good tumor targeting delivery capability.

Inventors

• ZHANG XU
• LIU WENHUI
• SHI HUI
• ZHANG JIAHUI

Assignees

• 江苏大学

Dates

Publication Date

20260508

Application Date

20260205

Claims (10)

1. 1. The preparation method of the composite nano system based on the ZIF-8 material-entrapped plant vesicle is characterized by comprising the following steps of incubating a zinc ion solution and a plant nano vesicle solution to obtain a zinc ion-PDVLNs mixed solution, mixing the zinc ion-PDVLNs mixed solution with a 2-methylimidazole solution for reaction, centrifuging and collecting precipitate; The concentration of the zinc ion solution is 0.07-0.10 mol/L, the concentration of the plant nano vesicle solution is 10 9 ~10 11 /mL, and the concentration of the 2-methylimidazole solution is 1-3 mol/L.
2. 2. The preparation method of claim 1, wherein the incubation time is 5-15 min.
3. 3. The preparation method according to claim 1, wherein the zinc ion-PDVLNs mixture is added dropwise to the 2-methylimidazole solution while stirring, and stirring is continued for 3-7 min after the completion of the dropwise addition, and then the mixture is allowed to stand for 20-40 min.
4. 4. The preparation method of claim 1, wherein the volume ratio of the zinc ion solution to the plant nano vesicle solution is (4-6): 1.
5. 5. The method of claim 1, wherein the method of preparing a zinc ion solution comprises dissolving zinc nitrate hexahydrate in water.
6. 6. The preparation method of claim 5, wherein the molar ratio of zinc nitrate hexahydrate to 2-methylimidazole is 1 (90-110).
7. 7. The method of claim 1, wherein the method of preparing a plant nanovesicle solution comprises dissolving plant nanovesicles in a PBS solution.
8. 8. The preparation method according to claim 1, wherein the rotational speed of the centrifugation is 10000-20000 rpm, and the time of the centrifugation is 3-7 min.
9. 9. The composite nanosystem obtained by the production method of any one of claims 1 to 8.
10. 10. The use of the composite nanosystem of claim 9 in the preparation of an anti-tumor targeted delivery drug.

Description

Preparation method and application of composite nano system based on ZIF-8 material-entrapped plant vesicles Technical Field The invention belongs to the technical field of nanomaterial construction and biomedical engineering, and particularly relates to a preparation method and application of a composite nano system based on ZIF-8 material-entrapped plant vesicles. Background Natural vesicles have been widely studied in recent years for delivery of various functional molecules such as drugs, nucleic acids, proteins, etc., due to their unique biofilm structure, natural component composition, and good biocompatibility. Plant-derived nanovesicles (plant-DERIVED VESICLE-like nanoparticles, PDVLNs) are one of the emerging candidates for nanodelivery vehicles because of their wide sources, high safety, and mass production. However, such vesicles generally have the problems of poor physical stability, fragile structure, easy clearance, short in vivo circulation time and the like, and the application efficiency of the vesicles in systemic delivery is limited. Metal-organic framework materials (Metal-Organic Frameworks, MOFs) are a class of porous crystalline materials composed of Metal ions and organic ligands through coordination bonds, where ZIF-8 (Zeolitic Imidazolate Framework-8) is a hotspot material in drug delivery research due to its good thermal stability, biocompatibility, and pH-responsive decomposition characteristics. ZIF-8 has stable structure in neutral environment, can be rapidly decomposed in weak acidic conditions (such as tumor tissue and lysosome), and has strong microenvironment response release capability. In recent years, there have been studies on attempts to combine ZIF-8 with natural substances such as proteins, enzymes and extracellular vesicles to improve the functionality and application adaptability thereof, but the prior art has problems such as uneven crystal coating, structural damage of vesicle membranes, and easiness in formation of large-sized aggregates in the aspect of incorporating flexible biological vesicles into the crystal structure of ZIF-8. Therefore, how to improve the stability, the efficient entrapment and delivery of flexible plant vesicles, prolong the half-life in vivo and give the environment responsiveness to the flexible plant vesicles is a technical problem to be solved. Disclosure of Invention Aiming at the technical problems, the first aim of the invention is to provide a preparation method of a composite nano system based on ZIF-8 material entrapped plant vesicles. The invention combines plant-derived nano vesicles with a metal organic framework, constructs a composite nano system with strong stability, centralized particle size distribution and complete structure, can respond and release in an acidic tumor microenvironment, and has good tumor targeting delivery capability. A second object of the present invention is to provide a composite nanosystem obtained by the above preparation method. The third object of the invention is to provide the application of the composite nano system in the targeted delivery of antitumor drugs. In order to achieve the above object, the present invention provides the following technical solutions: The invention provides a preparation method of a composite nano system based on ZIF-8 material-entrapped plant vesicles, which comprises the following steps of incubating a zinc ion solution and a plant nano vesicle solution to obtain a zinc ion-PDVLNs mixed solution, mixing the zinc ion-PDVLNs mixed solution with a 2-methylimidazole solution for reaction, centrifuging and collecting precipitate, wherein the concentration of the zinc ion solution is 0.07-0.10 mol/L, the concentration of the plant nano vesicle solution is 10 9~1011 pieces/mL, and the concentration of the 2-methylimidazole solution is 1-3 mol/L. As an embodiment, the incubation time is 5-15 min. As an implementation mode, the zinc ion-PDVLNs mixed solution is dripped into the 2-methylimidazole solution, the dripping is carried out while stirring, the stirring is continued for 3-7 min after the dripping is finished, and then the mixture is allowed to stand for reaction for 20-40 min. As an implementation mode, the volume ratio of the zinc ion solution to the plant nano vesicle solution is 4-6:1. As one embodiment, the method of preparing the zinc ion solution includes dissolving zinc nitrate hexahydrate in water. As an implementation mode, the mol ratio of the zinc nitrate hexahydrate to the 2-methylimidazole is 1:90-110. As one embodiment, the method of preparing the plant vesicle solution includes dissolving plant nanovesicles in PBS solution. As an implementation mode, the rotation speed of the centrifugation is 10000-20000 rpm, and the centrifugation time is 3-7 min. The invention also provides a composite nano system obtained by the preparation method. The invention also provides application of the composite nano system in targeted delivery of antitumor drugs. Com