Size-adjustable metal organic framework drug-loaded nano-particles as well as preparation method and application of size-adjustable metal organic framework drug-loaded nano-particles

Abstract

The invention discloses a size-adjustable metal organic framework drug-loaded nanoparticle as well as a preparation method and application thereof, and belongs to the technical field of medicines. According to the preparation method, through self-assembly reaction of one-step synthesis, zinc acetate is taken as a raw material, an aqueous solution of dimethylimidazole is taken as a reaction medium, and anthraquinone compounds are introduced to prepare the metal organic framework drug-loaded nanoparticles. According to the preparation method, the nucleation process of the ZIF-8 is regulated and controlled through the anthraquinone compound under the conditions that lattice arrangement of metal organic framework nanoparticles is not damaged and original synthesis conditions do not need to be changed, and accurate regulation and control of the size of the ZIF-8 is achieved. The size-regulated metal organic framework drug-loaded nanoparticles can more effectively exert the acid response degradation performance, so that the release behavior of the anthraquinone compound is better regulated and controlled, and the treatment effect of the anthraquinone compound is further improved.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a size-tunable metal-organic framework drug-loaded nanoparticle, its preparation method, and its application. Background Technology

[0002] With the development of nanotechnology, nanoparticle-mediated drug delivery systems have driven progress in the treatment of clinical diseases. Metal-organic frameworks have attracted much attention due to their high crystallinity, large specific surface area, and good biocompatibility. Among them, those composed of zinc ions (Zn0.05) are particularly noteworthy. 2+ The zeolite imidazole ester skeleton ZIF-8, formed by coordination of 2-methylimidazole with 2-methylimidazole, possesses advantages such as large specific surface area, high porosity, controllable structure, good thermal stability, and easy surface modification. It also exhibits good biocompatibility and pH sensitivity. ZIF-8 is stable under physiological conditions but degradable in acidic environments, making it an ideal carrier for targeted drug delivery and controlled release. Hydrophilic, hydrophobic, and amphiphilic drugs can be encapsulated in ZIF-8 through covalent or non-covalent interactions. Furthermore, due to its mild reaction conditions, ZIF-8 can also encapsulate biomolecules such as nucleic acids, antibodies, and bovine serum albumin, enhancing therapeutic efficacy while protecting their biological activity.

[0003] In recent years, inspired by nanosize-dependent biological effects, researchers have focused on achieving precise control over the particle size of ZIF-8. Particle size not only affects its transport behavior in vivo and its interaction with tissues and organs, but also determines material properties such as specific surface area, porosity, and degradation rate. Furthermore, nanosize-related biological effects can regulate the in vivo transport behavior of drug carriers, thereby influencing drug efficacy. Therefore, precise control of ZIF-8 size is crucial for designing efficient nanodelivery systems. Currently, the formation mechanism of ZIF-8 is mainly controlled by reaction parameters, nucleation, and crystal growth to regulate ZIF-8 particle size. Although these studies have promoted the development of ZIF-8, as a drug carrier, production costs, process complexity, and safety must be comprehensively considered. For example, while lowering the reaction temperature can control morphology and particle size, maintaining low temperatures (e.g., -40°C) requires expensive equipment and energy consumption. While introducing dimethyl sulfoxide, triethylamine, ammonia, or surfactants can yield particles with uniform size and diverse morphologies, the complex reaction systems may alter the physicochemical properties of drugs (especially biopharmaceuticals), or even damage active groups, interfering with efficacy. Furthermore, removing residual organic reagents and surfactants increases conversion costs and impacts safety. In summary, to better utilize the size-dependent nano-bioeffects of ZIF-8, energy-efficient, safe, and minimalist synthetic strategies should be explored to maximize the advantages of the carrier and accelerate clinical translation. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a size-tunable metal-organic framework drug-loaded nanoparticle, its preparation method and application, so as to solve the problems of high production cost, complex process and safety of ZIF-8 as a drug carrier in the prior art.

[0005] To achieve the above objectives, the present invention employs the following technical solution: A method for preparing size-tunable metal-organic framework drug-loaded nanoparticles includes the following steps: adding anthraquinone compounds and zinc acetate to a dimethylimidazole aqueous solution to obtain a reaction system; stirring the reaction system to obtain a reaction product; purifying the reaction product by washing with water and centrifugation to obtain metal-organic framework drug-loaded nanoparticles.

[0006] A further improvement of the present invention is that: Preferably, the stirring reaction temperature is room temperature, and the stirring reaction time is 0.2 to 2 hours.

[0007] Preferably, the concentration of zinc acetate in the reaction system is 1~3 mg / mL.

[0008] Preferably, the concentration of dimethylimidazole in the reaction system is 70~100 mg / mL.

[0009] Preferably, the mass ratio of zinc acetate to anthraquinone compounds is 20:1 to 2:1.

[0010] Preferably, the anthraquinone compound is any one of doxorubicin, emodin, aloe-rhein, or rhein.

[0011] A size-tunable metal-organic framework drug-loaded nanoparticle prepared by the above preparation method, wherein the size of the metal-organic framework drug-loaded nanoparticle is 70~600 nm.

[0012] Preferably, the anthraquinone compound loading in the metal-organic framework drug-loaded nanoparticles is 5-8%.

[0013] Preferably, the metal-organic framework drug-loaded nanoparticles have pH-responsive degradation properties.

[0014] An application of the above-mentioned size-tunable metal-organic framework drug-loaded nanoparticles for antibacterial and antitumor purposes.

[0015] Compared with the prior art, the present invention has the following beneficial effects: This invention discloses a method for preparing size-tunable metal-organic framework (MOF) drug-loaded nanoparticles. The method uses zinc acetate as a raw material and an aqueous solution of dimethylimidazole as the reaction medium, introducing anthraquinone compounds into conventional ZIF-8 nanoparticles through a one-step self-assembly reaction. This method achieves precise size control of ZIF-8 by regulating its nucleation process through anthraquinone compounds without disrupting the lattice arrangement of the MOF nanoparticles or altering the original synthesis conditions. The method successfully prepared size-controllable MOF drug-loaded nanoparticles E@Z. Specifically, the anthraquinone compounds significantly influence the size of ZIF-8; the integrity of the anthraquinone ring structure and the number of hydroxyl functional groups can regulate the nucleation rate and growth process of ZIF-8, thereby precisely controlling the size of E@Z. Furthermore, the nucleation process of ZIF-8 was regulated by anthraquinone compounds. The regulatory effect was closely related to the structural integrity of the anthraquinone ring, the feeding ratio, and the number of substituents in the molecular structure of the anthraquinone compounds. Specifically, the integrity of the anthraquinone ring structure is a prerequisite for its regulatory effect, while the number of hydroxyl groups on the anthraquinone ring and the concentration of the anthraquinone compounds further affect the size of the final nanoparticles. With increasing anthraquinone compound concentration and an increase in the number of hydroxyl groups on the anthraquinone ring surface, the particle size of E@Z showed a gradual decreasing trend. In addition, the prepared nanoparticles possess acid-responsive release properties, which can effectively improve the therapeutic effect of anthraquinone compounds.

[0016] The present invention also discloses a size-tunable metal-organic framework drug-loaded nanoparticle prepared by the above preparation method. The nanoparticle significantly improves the water solubility and targeting of anthraquinone compounds through the mediation of E@Z, thereby effectively enhancing their antibacterial and antitumor properties.

[0017] This invention also discloses the application of size-tunable metal-organic framework drug-loaded nanoparticles. Based on the chemical structural characteristics of anthraquinone compounds, these nanoparticles allow for flexible control of the E@Z size of ZIF-8-mediated drug-loaded nanoparticles, effectively overcoming the body's physiological and physical barriers, significantly enhancing their targeted accumulation ability at disease sites, improving cellular drug uptake efficiency, and ultimately significantly improving the therapeutic effects of anthraquinone compounds in antibacterial and antitumor applications. Attached Figure Description

[0018] Figure 1 TEM characterization images of ZIF-8 and E@Z; Figure 2 XRD characterization images of ZIF-8 and E@Z; Figure 3 Figure 1 shows the in vitro degradation characterization of ZIF-8 and E@Z. Figure 4The image shows the drug loading characterization of E@Z. Figure 5 Characterization diagram of in vitro drug release behavior for E@Z of different sizes; Figure 6 The antibacterial effect of E@Z was evaluated, where Emodin is emodin; Figure 7 The purpose of this study was to evaluate the antitumor effect of E@Z, where Emodin is emodin. Detailed Implementation

[0019] The present invention will now be described in further detail with reference to the accompanying drawings: To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions used in the specification and claims are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.

[0020] In this article, unless otherwise specified, “contains,” “includes,” “containing,” “has,” or similar terms cover the meanings of “composed of” and “mainly composed of,” for example, “A contains a” covers the meanings of “A contains a and others” and “A contains only a.”

[0021] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0022] The following examples use instruments and equipment conventional in the art. Experimental methods in the following examples, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. All raw materials used in the following examples are conventional commercially available products with specifications conventional in the art. In this specification and the following examples, unless otherwise specified, "%" refers to weight percentage, "parts" refers to parts by weight, and "ratio" refers to weight proportion.

[0023] This invention discloses a method for preparing size-tunable metal-organic framework drug-loaded nanoparticles E@Z. Specifically, the method involves a one-step self-assembly reaction at room temperature, using zinc acetate as a raw material and dimethylimidazole aqueous solution as the reaction medium, and preparing the nanoparticles by co-encapsulating anthraquinone compounds. The specific reaction steps include the following: (1) Using zinc acetate as raw material and dimethylimidazole aqueous solution as reaction medium, anthraquinone compounds were added under stirring conditions to obtain a reaction system. During the reaction, the anthraquinone compounds can not only act as binding templates for zinc ions and accelerate the nucleation process by reducing the Gibbs free energy, but also act as end-capping agents for the ZIF-8 {100} crystal plane to regulate crystal growth, so that the crystal can no longer grow. The more anthraquinone compounds are added, the more obvious the regulating effect is, so the size of the final E@Z can be controlled.

[0024] (2) After the reaction is completed, the product is purified by alternating water washing and centrifugation, and then vacuum dried to finally obtain high-purity drug-loaded nanoparticles.

[0025] In step (1) of this invention, the reaction temperature is room temperature and the reaction time is 0.2 ~ 2 h.

[0026] In step (1) of this invention, the concentration of zinc acetate in the reaction system ranges from 1 to 3 mg / mL.

[0027] In step (1) of this invention, the concentration of dimethylimidazole in the reaction system ranges from 70 to 100 mg / mL.

[0028] In step (2) of this invention, the mass ratio of zinc acetate to the drug is 20:1 to 2:1.

[0029] Specifically, the concentration range of dimethylimidazole and the mass of acetic acid and anthraquinone compounds must be within certain limits. If these limits are exceeded, it will be difficult to form size-tunable metal-organic framework drug-loaded nanoparticles E@Z, and the anthraquinone compounds will be unable to play a regulatory role.

[0030] In step (2) of this invention, the anthraquinone compound is any one of doxorubicin, emodin, aloe-rhein, or rhein.

[0031] A second aspect of the present invention discloses a size-tunable metal-organic framework drug-loaded nanoparticle E@Z prepared by the above preparation method, which achieves efficient encapsulation of anthraquinone compounds by ZIF-8.

[0032] The size of the prepared drug-loaded nanoparticles E@Z can be regulated by anthraquinone compounds, including doxorubicin, emodin, rhein, and aloe-rhein. On one hand, anthraquinone compounds act as binding templates for zinc ions, lowering the Gibbs free energy to accelerate nucleation; on the other hand, they act as end-capping agents for the ZIF-8 {100} crystal facets, regulating crystal growth. The regulatory effect depends on the structural integrity of the anthraquinone ring, the feed ratio, and the number of hydroxyl substituents in its molecular structure. The structural integrity of the anthraquinone core is fundamental to the regulatory effect, while the number of hydroxyl substituents and the concentration of the anthraquinone compound affect the final size of the drug-loaded nanoparticles. With increasing anthraquinone compound concentration and the number of hydroxyl groups, the particle size of E@Z decreases significantly.

[0033] The size-adjustable E@Z provided by this invention has a particle size between 70 and 600 nm.

[0034] The E@Z with adjustable size provided by this invention has a drug loading range of 5-8% for anthraquinone compounds.

[0035] A third aspect of this invention discloses the application of size-tunable metal-organic framework drug-loaded nanoparticles E@Z. The degradation characteristics of the final E@Z nanoparticles are controlled by both particle size and pH value during application. In a weakly acidic environment, due to the interaction between ZIF-8 and the acidic environment, combined with the interaction of the nanoparticle size itself, the small-sized E@Z can rapidly degrade and release the drug. Therefore, by adjusting the particle size and the weakly acidic environment, the drug release behavior of anthraquinone compounds can be further controlled.

[0036] The application of the size-tunable metal-organic framework drug-loaded nanoparticles E@Z in this invention significantly improves the antibacterial and antitumor effects of anthraquinone compounds through nanoparticle loading, particle size, and acid-responsive drug release behavior, providing a new theoretical basis for the clinical application of anthraquinone compounds.

[0037] The following description, in conjunction with specific embodiments, provides further details.

[0038] Example 1 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of doxorubicin (8 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 44 mg of zinc acetate, and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0039] Example 2 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of aloe-emodin (4 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 44 mg of zinc acetate and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0040] Example 3 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of emodin (6.25 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 44 mg of zinc acetate, and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0041] Example 4 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of emodin (12.5 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 44 mg of zinc acetate, and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0042] Example 5 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of rhein (8 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 44 mg of zinc acetate and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0043] Example 6 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of doxorubicin (4 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate, and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0044] Example 7 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of aloe-emodin (4 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0045] Example 8 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of emodin (4 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0046] Example 9 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of rhein (4 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate, and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0047] Example 10 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of doxorubicin (2 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0048] Example 11 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of aloe-emodin (2 mg) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0049] Example 12 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of emodin (2 mg / mL) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate, and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0050] Example 13 2 g of dimethylimidazole was added to 14 mL of pure water and sonicated for 15 min. Then, 1 mL of rhein (2 mg / mL) aqueous solution was added. After magnetic stirring for 15 min, the reaction solution was rapidly added to 10 mL of aqueous solution containing 40 mg of zinc acetate, and stirred at room temperature for 1.5 h. Finally, the final product was purified by washing with water and centrifugation, and the solid product was obtained by vacuum freeze-drying.

[0051] Example 14 1.75 g of dimethylimidazole and 2 mg of rhein were added to 15 mL of deionized water and mixed thoroughly. The reaction solution was then quickly added to 10 mL of an aqueous solution containing 25 mg of zinc acetate, and stirred at room temperature for 12 min. After the reaction was complete, the product was purified by washing with deionized water and centrifugation, and then the solid target product was obtained by vacuum freeze-drying.

[0052] Example 15 1.75 g of dimethylimidazole and 8 mg of rhein were added to 15 mL of deionized water and mixed thoroughly. The reaction solution was then quickly added to 10 mL of an aqueous solution containing 75 mg of zinc acetate, and stirred at room temperature for 12 min. After the reaction was complete, the product was purified by washing with deionized water and centrifugation, and then the solid target product was obtained by vacuum freeze-drying.

[0053] Example 16 2.5 g of dimethylimidazole and 2 mg of rhein were added to 15 mL of deionized water and mixed thoroughly. The reaction solution was then quickly added to 10 mL of an aqueous solution containing 40 mg of zinc acetate, and stirred at room temperature for 12 min. After the reaction was complete, the product was purified by washing with deionized water and centrifugation, and then the solid target product was obtained by vacuum freeze-drying.

[0054] Example 17 2.5 g of dimethylimidazole and 8 mg of rhein were added to 15 mL of deionized water and mixed thoroughly. The reaction solution was then quickly added to 10 mL of an aqueous solution containing 75 mg of zinc acetate, and stirred at room temperature for 12 min. After the reaction was complete, the product was purified by washing with deionized water and centrifugation, and then the solid target product was obtained by vacuum freeze-drying.

[0055] Example 18 2.5 g of dimethylimidazole and 8 mg of rhein were added to 15 mL of deionized water and mixed thoroughly. The reaction solution was then quickly added to 10 mL of an aqueous solution containing 75 mg of zinc acetate, and stirred at room temperature for 30 min. After the reaction was complete, the product was purified by washing with deionized water and centrifugation, and then the solid target product was obtained by vacuum freeze-drying.

[0056] Example 19 1.75 g of dimethylimidazole and 3.75 mg of rhein were added to 15 mL of deionized water and mixed thoroughly. The reaction solution was then quickly added to 10 mL of an aqueous solution containing 75 mg of zinc acetate, and stirred at room temperature for 12 min. After the reaction was complete, the product was purified by washing with deionized water and centrifugation, and then the solid target product was obtained by vacuum freeze-drying.

[0057] Example 20 2.5 g of dimethylimidazole and 20 mg of rhein were added to 15 mL of deionized water and mixed thoroughly. The reaction solution was then quickly added to 10 mL of an aqueous solution containing 40 mg of zinc acetate, and stirred at room temperature for 12 min. After the reaction was complete, the product was purified by washing with deionized water and centrifugation, and then the solid target product was obtained by vacuum freeze-drying.

[0058] The effect of the anthraquinone compound emodin on the size regulation of ZIF-8 cells under different dosage ratios in Examples 3 and 4 was investigated by TEM. The results showed that the particle size of the obtained E@Z cells decreased significantly with increasing emodin concentration, as detailed in the attached figure. Figure 1 As shown.

[0059] XRD analysis was performed on the lattice characteristics of drug-loaded nanoparticles E@Z of different sizes obtained in Examples 3 and 4. The results showed that the anthraquinone compound emodin did not affect the lattice arrangement of ZIF-8. Compared with blank ZIF-8, the drug-loaded nanoparticles had the same lattice peak arrangement. The results are shown in the attached figure. Figure 2 As shown.

[0060] The degradation behavior of drug-loaded nanoparticles E@Z of different sizes prepared in Examples 3 and 4 was investigated by TEM in a weakly acidic medium. The results showed that in the acidic medium, the degradation rate of E@Z increased with decreasing nanoparticle size. The results are shown in the attached figure. Figure 3 As shown.

[0061] The drug loading of emodin in the drug-loaded nanoparticles E@Z of different sizes prepared in Examples 3 and 4 was determined and analyzed using a UV-Vis spectrophotometer. The results are as follows: Figure 4 As shown, the drug loading of the drug-loaded nanoparticles E1@Z prepared in Example 3 is about 5%, and the drug loading of the drug-loaded nanoparticles E2@Z prepared in Example 4 is about 8%.

[0062] The drug release behavior of drug-loaded nanoparticles E@Z of different sizes prepared in Examples 3 and 4 in a weakly acidic medium was measured and analyzed using a UV-Vis spectrophotometer. The results are attached. Figure 5 As shown, the release of emodin from E@Z is significantly accelerated as the nanoparticle size decreases.

[0063] Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Enterococcus were used as test strains to evaluate the antibacterial properties of E@Z prepared in Example 4. (See attached...) Figure 6 As shown, the results indicate that E@Z inhibited bacterial growth to some extent and broadened the antibacterial spectrum of emodin.

[0064] The antitumor effects of drug-loaded nanoparticles E@Z of different sizes prepared in Examples 3 and 4 were investigated using an orthotopic breast cancer mouse model. (See attached image.) Figure 7 As shown, the results indicate that ZIF-8-mediated E@Z significantly enhances the antitumor effect of emodin. Specifically, the combination of E@Z of different sizes induced apoptosis in more tumor cells by regulating the release behavior of emodin, thereby effectively inhibiting tumor growth and progression.

[0065] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing size-tunable metal-organic framework drug-loaded nanoparticles, characterized in that, The specific steps are as follows: anthraquinone compounds and zinc acetate are added to a dimethylimidazole aqueous solution to obtain a reaction system. The reaction system is stirred to carry out the reaction and obtain the reaction product. The reaction product is purified by washing with water and centrifugation to obtain metal-organic framework drug-loaded nanoparticles.

2. The method for preparing size-tunable metal-organic framework drug-loaded nanoparticles according to claim 1, characterized in that, The stirring reaction was carried out at room temperature for 0.2 to 2 hours.

3. The method for preparing size-tunable metal-organic framework drug-loaded nanoparticles according to claim 1, characterized in that, The concentration of zinc acetate in the reaction system is 1~3 mg / mL.

4. The method for preparing size-tunable metal-organic framework drug-loaded nanoparticles according to claim 1, characterized in that, The concentration of dimethylimidazole in the reaction system is 70~100 mg / mL.

5. The method for preparing size-tunable metal-organic framework drug-loaded nanoparticles according to claim 1, characterized in that, The mass ratio of zinc acetate to anthraquinone compounds is 20:1 to 2:

1.

6. The method for preparing size-tunable metal-organic framework drug-loaded nanoparticles according to claim 1, characterized in that, The anthraquinone compound is any one of doxorubicin, emodin, aloe-rhein, or rhein.

7. A size-tunable metal-organic framework drug-loaded nanoparticle prepared by any one of claims 1-6, characterized in that, The size of the metal-organic framework drug-loaded nanoparticles is 70~600 nm.

8. The size-tunable metal-organic framework drug-loaded nanoparticles according to claim 7, characterized in that, The anthraquinone compounds in the metal-organic framework drug-loaded nanoparticles have a loading capacity of 5-8%.

9. The size-tunable metal-organic framework drug-loaded nanoparticles according to claim 7, characterized in that, The metal-organic framework drug-loaded nanoparticles exhibit pH-responsive degradation characteristics.

10. An application of the size-tunable metal-organic framework drug-loaded nanoparticles according to claim 7, characterized in that, Used for antibacterial and antitumor purposes.

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