Carboxylic acid ligand-copper metal organic framework nano material and preparation method and injection thereof

Abstract

The invention relates to a carboxylic acid ligand-copper metal organic framework nano material, a preparation method thereof and an injection. The carboxylic acid ligand-copper metal organic framework nano material is of a polycrystal MOF structure formed by connecting carboxylic acid ligands and copper ions through coordinate bonds; the carboxylic acid ligand comprises at least one of dicarboxylic acid and tricarboxylic acid; preferably, the dicarboxylic acid comprises at least one of itaconic acid and fumaric acid, and the tricarboxylic acid comprises at least one of aconitic acid and citric acid; the valence states of the copper ions comprise zero valence, + 1 valence and + 2 valence; preferably, based on the total amount of the copper ions being 100 at%, the total content of Cu0 and Cu + is 85-90 at%, and the content of Cu2 + is 10-15 at%.

Description

Technical Field

[0001] The invention belongs to the technical field of nano drug materials, and specifically relates to a carboxylic acid ligand-copper metal organic framework nano material and a preparation method and injection thereof. Background Art

[0002] Itaconic acid (IA) is a metabolite catalyzed by an enzyme encoded by immune response gene 1 (Irg1) in the mitochondrial matrix. In recent years, it has been widely regarded as an important immune metabolic regulator. Studies have shown that itaconic acid is significantly upregulated in immune cells (such as macrophages) and has multiple biological activities in anti-inflammatory, antioxidant, metabolic regulation and antibacterial aspects. These properties make it show great potential in the treatment of inflammatory diseases, metabolic disorders and infectious diseases.

[0003] Although itaconic acid has shown significant therapeutic effects in animal models and in vitro experiments, its clinical application is still in the exploratory stage. First, as a small molecule metabolite, itaconic acid is easily metabolized and cleared rapidly in the body, which may lead to insufficient local concentration or off-target effects caused by systemic distribution. Therefore, developing efficient delivery systems (such as nanoparticles, liposomes, or cell-based delivery strategies) to improve its targeting and stability is one of the focuses of future research. In addition, the long-term safety and potential side effects of itaconic acid still need to be fully evaluated. Although animal models and in vitro experiments show that it has good biocompatibility, itaconic acid may have unpredictable effects on normal cell metabolism, immune homeostasis, or microbiome in the complex human environment. Therefore, future studies should combine multi-omics technologies to comprehensively evaluate its biological effects and verify its safety and effectiveness through rigorous clinical trials. Therefore, how to improve the specific delivery of itaconic acid, optimize its pharmacokinetic properties, and verify its effectiveness and safety in humans are key issues that need to be solved in future research and translational medicine. Future research should focus on developing efficient delivery systems, exploring the in-depth details of its mechanism of action, and verifying its therapeutic potential through clinical trials, thereby providing new treatment strategies for inflammatory diseases, metabolic diseases, and infectious diseases.

[0004] Transition metals (such as iron, copper, manganese, etc.) have important application values in the field of nanomaterial preparation, especially in nanodrug design, due to their unique electronic structures, coordination abilities, and catalytic activities. Transition metals can form stable coordination bonds with various organic ligands (such as carboxylic acids, amines, or nitrogen-containing heterocyclic compounds), thereby constructing metal-organic frameworks (MOFs) or coordination polymers with controllable structures and diverse functions. These materials not only have high specific surface areas, adjustable pore sizes, and excellent stabilities, but also can achieve specific biological or chemical functions through surface modification or functionalization. For example, transition metal nanomaterials exhibit significant advantages in catalytic reactions, gas adsorption, drug loading and release, etc.

[0005] However, although transition metals show broad application prospects in the field of nanodrugs, they still face some challenges in practical applications. For example, the potential toxicity, long-term stability, and behavior in complex biological environments of transition metals still need to be studied in depth. Summary of the Invention

[0006] Aiming at the above technical problems, the purpose of the present invention is to provide a nanodrug carrier material with increased specific targeting, controllable release, and high biocompatibility of small molecule drugs, as well as its preparation method and injection solution.

[0007] In the first aspect, the present invention provides a carboxylic acid ligand-copper metal-organic framework nanomaterial, and the carboxylic acid ligand-copper metal-organic framework nanomaterial is a MOF structure with polycrystals formed by connecting a carboxylic acid ligand and copper ions through coordination bonds; The carboxylic acid ligand includes at least one of dicarboxylic acids and tricarboxylic acids; preferably, the dicarboxylic acid includes at least one of itaconic acid and fumaric acid, and the tricarboxylic acid includes at least one of aconitic acid and citric acid; The valence states of the copper ions include 0, +1, and +2; preferably, based on the total amount of copper ions being 100 at%, the total content of Cu 0 and Cu + is 85 - 90 at%, and the content of Cu 2+ is 10 - 15 at%.

[0008] Preferably, the mass ratio of the carboxylic acid ligand in the carboxylic acid ligand-copper metal-organic framework nanomaterial is 47 - 88 wt%, preferably 86 - 88 wt%, and the mass ratio of copper is 12 - 53 wt%, preferably 12 - 14 wt%.

[0009] Preferably, the carboxylic acid ligand-copper metal-organic framework nanomaterial has a spherical morphology and an average particle size of 4 - 5 nm.

[0010] Second aspect, the present invention provides a method for preparing the above-mentioned carboxylic acid ligand-copper metal-organic framework nanomaterial, and the preparation method includes the following steps: adding a copper salt solution to a carboxylic acid ligand solution and mixing, while maintaining condensation reflux; then, after washing and drying, the carboxylic acid ligand-copper metal-organic framework nanomaterial is obtained.

[0011] Preferably, the copper salt is at least one of cupric acetate anhydrous, cupric acetate monohydrate, cupric acetate dihydrate, copper hydroxide, and copper chloride; wherein, the concentration of the copper salt solution is 5-25 mg / mL, preferably 5-20 mg / mL; the concentration of the carboxylic acid ligand solution is 5-20 mg / mL, preferably 10-15 mg / mL; the molar ratio of the carboxylic acid ligand to the copper salt is 1.5:(1-3), preferably 1.5:(1.5-3), more preferably 1.5:(2-3), and most preferably 1.5:2.5.

[0012] Preferably, the parameters of the condensation reflux include: rotation speed 300-400 rpm, temperature 110-125 °C, and time 4-5 h.

[0013] Preferably, the drying method is vacuum freeze-drying, the temperature is -90 to -70 °C, and the time is 6-12 h.

[0014] Third aspect, the present invention provides an injection of a carboxylic acid ligand-copper metal-organic framework nanomaterial, and the injection of the carboxylic acid ligand-copper metal-organic framework nanomaterial includes: a biocompatible solution, and a carboxylic acid ligand-copper metal-organic framework nanomaterial dispersed in the biocompatible solution.

[0015] Preferably, the biocompatible solution includes at least one of physiological saline and phosphate buffer solution.

[0016] Preferably, the concentration of the carboxylic acid ligand-copper metal-organic framework nanomaterial in the injection is 10-30 mg / mL.

[0017] Beneficial effects (1) The carboxylic acid ligand-copper metal-organic framework nanomaterial provided by the present invention forms a stable metal-based framework structure through the coordination of the carboxyl group of the carboxylic acid ligand with copper ions, and has a high specific surface area and multifunctional characteristics; this structure not only facilitates the efficient loading of drug molecules, but also provides an ideal platform for applications such as catalytic reactions and gas adsorption; (2) The preparation process of the present invention is simple, pollution-free, high-yield, low-cost, easy to mass-produce, and has a wide application prospect in the catalytic field; (3) The anti-inflammatory and antioxidant properties of carboxylic acid ligands such as itaconic acid are combined with the catalytic activity of copper ions, endowing the material with multifunctionality. For example, copper ions can generate reactive oxygen species (ROS) through the Fenton reaction, while itaconic acid and the like can regulate cell metabolism. The synergistic effect of the two can significantly enhance the application potential of the material in disease treatment. This material can not only be applied to the catalytic field, but also provides new ideas and technical support for the design and application of drug delivery and disease treatment. Description of the Drawings

[0018] Figure 1 TEM image of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1; Figure 2 Mapping elemental distribution map and EDS energy spectrum analysis map of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1; Figure 3 XRD pattern of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1; Figure 4 Zeta potential analysis diagram of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1; Figure 5 Fourier transform infrared spectroscopy (FT-IR) analysis diagram of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1; Figure 6 XPS pattern of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1; Figure 7 Thermogravimetric analysis curve of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1; Figure 8 Test results of electron spin resonance (ESR) of the reaction scavenging system of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1 with hydroxyl radicals; Figure 9 TEM image of the itaconic acid-based MOF material prepared in Comparative Example 1; Figure 10 TEM image of the itaconic acid-based MOF material prepared in Comparative Example 2; Figure 11 TEM image of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 2; Figure 12 TEM image of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 3; Figure 13TEM image of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 4; Figure 14 TEM image of itaconic acid-based MOF material prepared in Comparative Example 3; Figure 15 TEM image of itaconic acid-based MOF material prepared in Comparative Example 4; Figure 16 TEM image of itaconic acid-based MOF material prepared in Comparative Example 5. Detailed implementation manners

[0019] The present invention will be further described below through the following implementation manners. It should be understood that the following implementation manners are only used to illustrate the present invention and do not limit the present invention.

[0020] First, the present invention provides a carboxylic acid ligand-copper metal-organic framework nanomaterial. Among them, the carboxylic acid ligand-copper metal-organic framework nanomaterial can be a MOF structure with polycrystals formed by connecting a carboxylic acid ligand and copper ions through coordination bonds.

[0021] In some embodiments, the carboxylic acid ligand may include at least one of dicarboxylic acids and tricarboxylic acids; preferably, the dicarboxylic acid may include at least one of itaconic acid and fumaric acid, and the tricarboxylic acid may include at least one of aconitic acid and citric acid.

[0022] Among them, the structural formula of itaconic acid is: C5H6O4, the structural formula of fumaric acid is: C4H4O4, the structural formula of aconitic acid is: C6H6O6, including cis-aconitic acid or / and trans-aconitic acid, and cis-aconitic acid is trans-aconitic acid is the structural formula of citric acid is: C6H8O7,

[0023] In some embodiments, the valence state of the copper ions may include 0 valence, +1 valence, and +2 valence; preferably, based on the total amount of copper ions being 100 at%, the total content of Cu 0 and Cu + can be 85-90 at%, and the content of Cu 2+ can be 10-15 at%.

[0024] Among them, zero-valent copper (Cu 0 ) has good electrical conductivity and catalytic activity and is suitable for use in electron transport or catalytic reactions; monovalent copper (Cu + ) plays an important role in coordination chemistry and catalytic reactions, can stabilize the coordination structure and participate in redox reactions; divalent copper (Cu 2+) has a relatively high oxidizing property, which can enhance the redox activity of the material. However, if the content is too high, it may lead to a decrease in the stability of the material. Additionally, Cu 0 and Cu + with too high contents will result in: (1) Decreased material stability: Cu 0 and Cu + are easily oxidized in the air, leading to unstable material properties; (2) Insufficient redox activity: If the content of Cu 2+ is too low, it may reduce the redox activity of the material, affecting its applications in catalysis or electrochemistry. Cu 0 and Cu + with too low contents will result in: (1) Decreased conductivity: Too low content of Cu 0 will reduce the conductivity of the material, affecting its applications in electronic devices; (2) Insufficient catalytic activity: Too low content of Cu + may reduce the catalytic activity of the material, affecting its reaction efficiency. Cu 2+ with too high content will result in: (1) Decreased material stability: Cu 2+ has strong oxidizing property, and too high content may cause the material to be unstable in the air; (2) Increased toxicity: Too high content of Cu 2+ may increase the biological toxicity of the material, restricting its applications in biomedicine. Cu 2+ with too low content will result in insufficient redox activity of the material: Too low content of Cu 2+ may reduce the redox activity of the material, affecting its performance in catalysis or electrochemistry.

[0025] In some embodiments, the mass ratio of the carboxylic acid ligand in the carboxylic acid ligand-copper metal-organic framework nanomaterial can be 47-88 wt%, preferably 86-88 wt%, and the mass ratio of copper can be 12-53 wt%, preferably 12-14 wt%.

[0026] By controlling the two components within a suitable mass ratio range, the functions of metal ions (such as functions of drug carriers, catalysis, imaging, etc.) and the requirements of ligand stability, structural integrity, etc. can be balanced. If the mass ratio of metal ions is too large, it is easy to cause toxicity to cells or the human body, and a relatively high metal content may increase side effects; if the mass ratio of metal ions is too small, it will affect the therapeutic effect of the drug and reduce its multifunctionality (drug delivery, imaging, catalysis, etc.). If the mass ratio of the carboxylic acid ligand is too large, it will increase the drug loading capacity, but at the same time will affect the coordination effect between the ligand and metal ions, resulting in a decrease in the drug release efficiency or targeting.

[0027] In some embodiments, the carboxylic acid ligand-copper metal-organic framework nanomaterial can have a spherical morphology, and the average particle size can be 4-5 nm.

[0028] Too small particle size will lead to: (1) Excessively high surface energy: As the particle size decreases, the surface energy increases, which may cause instability or agglomeration of the material. The high surface energy may also trigger oxidation, degradation or other unstable behaviors of the material, affecting its long-term performance; (2) Increased agglomeration phenomenon: Nanomaterials with too small particle size are prone to agglomeration, forming larger particles or particle clusters, which will weaken their original excellent properties (such as catalytic activity, adsorption capacity, etc.). If the particle size is too large, it will lead to a reduction in its specific surface area, lower reactivity and catalytic efficiency, and reduce the stability and transport efficiency of the material. Therefore, in order to ensure that the nanomaterials have the best performance, it is necessary to control their particle size within a reasonable range, which can not only utilize their large specific surface area, but also avoid problems caused by too small particle size such as quantum effects or instability.

[0029] The carboxylic acid ligand-copper metal-organic framework nano-MOFs material provided by the present invention is a crystalline structure compound formed by connecting Cu ions and organic carboxylic acid ligands through coordination bonds. The coordination structure determines the coordination environment of the metal binding to the acid. The coordination structure of Cu is often four-coordinated or six-coordinated, with multiple coordination sites. Therefore, it is easy to form a spatially configured structure with small molecules containing carboxylic acids such as itaconic acid in space, that is, a MOF material with a metal-organic framework structure.

[0030] Hereinafter, an exemplary preparation method of the carboxylic acid ligand-copper metal-organic framework nanomaterial provided by the present invention will be described. Among them, the preparation method may include the following steps: adding a copper salt solution to a carboxylic acid ligand solution and mixing, and maintaining reflux condensation; then, after washing and drying, the carboxylic acid ligand-copper metal-organic framework nanomaterial is obtained.

[0031] In some embodiments, the copper salt may be at least one of anhydrous copper acetate, copper acetate monohydrate, copper acetate dihydrate, copper hydroxide and copper chloride; wherein, the concentration of the copper salt solution may be 5-25 mg / mL, preferably 5-20 mg / mL.

[0032] Among them, the limitations on the types and solution concentrations of the copper salts are determined according to the solubility, reaction activity of the copper salts, and the structural and performance requirements of the finally prepared materials. These selections not only affect the choice of copper source, but also directly affect the reaction rate, material purity, and performance of the final product during the reaction process. If the solution concentration is too high, the solubility of the copper salt will exceed its dissolution limit, resulting in precipitation in the solution, affecting the uniformity. At the same time, too high a concentration of copper ions may lead to excessive nucleation, resulting in a larger particle size of the generated nanomaterials, or in some cases, may lead to irregular or aggregated structures; moreover, too high a concentration may cause excessive aggregation of metal ions, forming metal agglomeration or granulation phenomena, thus affecting the catalytic performance and stability of the final material. If the solution concentration is too low, the reaction rate will be too slow to quickly generate the required copper source, resulting in a too long synthesis time and a low yield. At the same time, a lower concentration may also not provide enough copper ions to achieve the required material properties; moreover, too low a concentration of copper ions may lead to insufficient nucleation, and the formed nanomaterials may not be uniform enough, or even lead to an incomplete or unstable material structure.

[0033] In some embodiments, the concentration of the carboxylic acid ligand solution can be 5 - 20 mg / mL, preferably 10 - 15 mg / mL.

[0034] Carboxylic acid ligand molecules are usually used to form coordination bonds with metal ions to form stable nanostructures. To a certain extent, a higher proportion of ligands helps to enhance stability and avoid the disordered accumulation or aggregation of metal ions. However, if the concentration of the carboxylic acid ligand is too high, it will increase the drug loading capacity, but at the same time may affect the coordination effect between the ligand and the metal ions, and may lead to a decrease in the drug release efficiency or targeting. If the ligand concentration is too low, it may not provide enough ligand molecules to effectively coordinate with the metal ions, resulting in incomplete formation of the metal-organic framework or an unstable framework structure; in addition, a low concentration may lead to too slow an interaction between the metal ions and the ligand, resulting in too low a reaction rate, and it may take a longer time to achieve the expected reaction result, and the yield may be low; moreover, too low a concentration may make it difficult for the ligand to fully cover the metal ions, resulting in an incomplete MOF structure finally synthesized, affecting the catalytic performance, adsorption performance, etc. of the material.

[0035] In some embodiments, the molar ratio of the carboxylic acid ligand to the copper salt can be 1.5:(1 - 3), preferably 1.5:(1.5 - 3), more preferably 1.5:(2 - 3), and most preferably 1.5:2.5. Under the condition of this molar ratio, better MOF-like nanoparticles with regular shapes and uniform distribution of metal ion elements can be formed.

[0036] If the molar ratio of the two is too small (an excessive amount of copper salt), the following problems will occur: (1) Excessive metal leads to aggregation: Too many copper ions may not be fully coordinated by ligand molecules, and some metal ions may not be effectively incorporated into the framework, easily aggregating to form metal clusters or particles. This will result in an irregular MOF structure or a decrease in porosity, thereby affecting the stability and performance of the material; (2) Insufficient ligand coordination: In the case of excessive copper salt, although there are sufficient copper ions, not all copper ions may be fully coordinated with the ligand. This will lead to an uneven coordination state of the ligand in the reaction system, affecting the structural uniformity and ultimate functionality of the MOF; (3) Incomplete reaction: If there is too much copper salt, some copper ions may not effectively participate in the formation of the MOF structure during the reaction, resulting in an uneven distribution of metal ions in the material. Even some copper ions may exist in the form of free ions, affecting the final performance of the material; (4) Unstable structure: Excessive copper salt may cause the framework structure to become unstable. Especially for some MOF materials with high requirements for pore channels and surface energy, too much copper may interfere with the formation of the framework, resulting in irregular pore structures and affecting properties such as adsorption and catalysis. If the molar ratio of the two is too large (an insufficient amount of copper salt), the following problems will occur: (1) Insufficient metal ion coordination: A smaller amount of copper salt may not provide enough metal ions for all ligands, resulting in some ligands not being coordinated with metal ions and unable to form a metal-organic framework, thus making the structure of the MOF incomplete or unstable; (2) Incomplete structure: In the case of insufficient copper salt, the metal ions may be unevenly distributed, leading to irregular structures and poor porosity of the synthesized MOF particles, or the inability to form the desired framework structure. In this case, the final obtained material may lack ideal functionalities such as catalysis and adsorption; (3) Insufficient nucleation: A smaller amount of copper salt will lead to insufficient nucleation during the reaction, and it may take a longer reaction time to complete the assembly of the framework. This not only increases the time cost but also may result in a low yield, affecting production efficiency; (4) Too slow reaction rate: When there is insufficient copper salt, the concentration of copper ions is too low, which may lead to too slow a reaction rate, resulting in incomplete formation of the metal-organic framework during the synthesis process and affecting the final quality.

[0037] In some embodiments, the parameters of the condensation reflux include: a rotation speed of 300 - 400 rpm, a temperature of 110 - 125 °C, and a time of 4 - 5 h.

[0038] By controlling the parameters of the condensation reflux within an appropriate range, it is possible to ensure the full progress of the reaction while avoiding side reactions and excessive particle growth. Too high or too low a temperature, too long or too short a time may all have an adverse impact on the formation of the coordination bond between metal ions and carboxylic acid ligands and the successful preparation of the nano-drug. Therefore, strictly controlling these parameters is crucial for obtaining high-quality and stable nano-drugs.

[0039] In some embodiments, the washing liquid used for washing can be a mixture of water and ethanol, and the number of washing times can be 2 to 3 times.

[0040] In some embodiments, the drying method can be vacuum freeze-drying, the temperature can be -90 to -70 °C, and the time can be 6 to 12 h.

[0041] As an example, the preparation method of itaconic acid-copper metal-organic framework nanomaterials can include the following steps: (1) Dissolve equimolar amounts of itaconic acid and copper salt in deionized water and ethanol liquids with a volume ratio of 2:5 respectively to obtain an itaconic acid solution and a copper salt solution. Add the copper salt solution to the solution system of itaconic acid through a Pasteur pipette, and ultrasonically stir and mix at room temperature for 1 min to obtain a mixed solution; (2) Keep the mixed solution under reflux condensation (300 rpm, 120 °C, 4 h), then wash it 2 to 3 times with a mixture of water and ethanol, and then vacuum freeze-dry to obtain itaconic acid-copper metal-organic framework nanomaterials.

[0042] The synthesis process of the carboxylic acid ligand-copper metal-organic framework nanomaterials provided by the present invention is simple, the conditions are mild, there is no pollution, the yield is high, the cost is low, and it is easy to mass-produce, providing a new functional material platform for fields such as catalytic reactions, and having excellent clinical application prospects in the biomedical field. Moreover, by optimizing the material design (such as surface modification, size regulation or composite structure construction), the biocompatibility and targeting of transition metal nanodrugs can be further improved, thus promoting their applications in fields such as energy, environment and biomedicine.

[0043] In addition, the present invention also provides an injection of carboxylic acid ligand-copper metal-organic framework nanomaterials. Among them, the injection of carboxylic acid ligand-copper metal-organic framework nanomaterials can include: a biocompatible solution, and carboxylic acid ligand-copper metal-organic framework nanomaterials dispersed in the biocompatible solution.

[0044] In some embodiments, the biocompatible solution can include at least one of normal saline and phosphate buffer solution.

[0045] In some embodiments, the concentration of the carboxylic acid ligand-copper metal-organic framework nanomaterials in the injection can be 10 to 30 mg / mL.

[0046] By controlling the concentration of the carboxylic acid ligand-copper metal-organic framework nanomaterials in the injection within an appropriate range, the therapeutic effect and biocompatibility of the drug can be effectively balanced. If the concentration is too high, it may increase toxicity and injection difficulty; while if the concentration is too low, it may lead to insufficient drug efficacy and even treatment failure. Therefore, controlling the appropriate concentration range is the key to ensuring the drug effect and safety.

[0047] The following are further examples to illustrate the present invention in detail. It should also be understood that the following examples are only used to further illustrate the present invention and should not be construed as limiting the protection scope of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention all fall within the protection scope of the present invention. The specific process parameters and the like in the following examples are also only an example within a suitable range, that is, those skilled in the art can make selections within a suitable range through the description herein, rather than being limited to the specific values in the following examples.

[0048] Example 1 (1) Dissolve 0.2 g of itaconic acid in 20 mL of deionized water to obtain an itaconic acid solution (10 mg / mL); dissolve 0.5 g of copper acetate monohydrate in 50 mL of absolute ethanol to obtain a copper acetate monohydrate solution (10 mg / mL); control the molar ratio of itaconic acid to copper acetate to be 1.5:2.5, and gradually add the copper acetate solution to the itaconic acid solution, and ultrasonically stir and mix evenly at room temperature for 1 min to obtain a mixed solution; (2) Add the above mixed solution to a three-necked flask, place a magnetic stir bar, and carry out reflux condensation at 300 rpm and 120 °C for 4 h, then wash with water and ethanol 2 - 3 times, centrifuge (12,000 rpm, 15 min) to collect the product, and after vacuum freeze-drying, obtain itaconic acid-copper metal-organic framework nanomaterial (IA-Cu).

[0049] Example 2 The preparation process of the itaconic acid-based MOF material in this example refers to Example 1, with the only difference being: In step (1), the concentration ratio of itaconic acid to copper salt is reduced by 2 times, that is, the concentration of the itaconic acid solution is 5 mg / mL, and the concentration of the copper acetate monohydrate solution is 5 mg / mL (the molar ratio of itaconic acid to copper acetate is 1.5:2.5).

[0050] Example 3 The preparation process of the itaconic acid-based MOF material in this example refers to Example 1, with the only difference being: In step (1), the concentration of the itaconic acid solution is 15 mg / mL, and the concentration of the copper acetate monohydrate solution is 18.38 mg / mL (the molar ratio of itaconic acid to copper acetate is 1.5:3).

[0051] Example 4 The preparation process of the itaconic acid-based MOF material in this example refers to Example 1, with the only difference being: In step (1), the concentration of the itaconic acid solution is 10 mg / mL, and the concentration of the copper acetate monohydrate solution is 6.16 mg / mL (the molar ratio of itaconic acid to copper acetate is 1.5:1.5).

[0052] Comparative Example 1 The preparation process of the itaconic acid-based MOF material in this comparative example is referred to Example 1, with the only difference being that: In step (1), the concentrations of itaconic acid and copper salt are increased by 5 times, that is, the concentration of the itaconic acid solution is 50 mg / mL, and the concentration of the copper acetate monohydrate solution is 50 mg / mL (the molar ratio of itaconic acid to copper acetate is 1.5:2.5).

[0053] Comparative Example 2 The preparation process of the itaconic acid-based MOF material in this comparative example is referred to Example 1, with the only difference being that: In step (1), the concentrations of itaconic acid and copper salt are increased by 3 times, the concentration of the itaconic acid solution is 30 mg / mL, and the concentration of the copper acetate monohydrate solution is 30 mg / mL (the molar ratio of itaconic acid to copper acetate is 1.5:2.5).

[0054] Comparative Example 3 The preparation process of the itaconic acid-based MOF material in this comparative example is referred to Example 1, with the only difference being that: In step (1), the concentration of the itaconic acid solution is 30 mg / mL, and the concentration of the copper acetate monohydrate solution is 6.12 mg / mL (the molar ratio of itaconic acid to copper acetate is 1.5:0.5).

[0055] Comparative Example 4 The preparation process of the itaconic acid-based MOF material in this comparative example is referred to Example 1, with the only difference being that: In step (1), 0.2 g of itaconic acid is dissolved in 20 mL of deionized water to obtain an itaconic acid solution (10 mg / mL); 0.434 g of copper nitrate is dissolved in 17.36 mL of absolute ethanol to obtain a copper nitrate solution (25 mg / mL); the molar ratio of itaconic acid to copper nitrate is controlled to be 1.5:2.5.

[0056] Comparative Example 5 The preparation process of the itaconic acid-based MOF material in this comparative example is referred to Example 1, with the only difference being that: In step (1), 0.2 g of itaconic acid is dissolved in 20 mL of deionized water to obtain an itaconic acid solution (10 mg / mL); 0.794 g of copper acetate monohydrate is dissolved in 31.76 mL of absolute ethanol to obtain a copper acetate monohydrate solution (25 mg / mL); the molar ratio of itaconic acid to copper acetate is controlled to be 1.5:5.

[0057] Figure 1 It is the TEM image of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1. It can be seen from the figure that the synthesized itaconic acid-based MOF nanomaterial shows a regular spherical morphology, uniform particle size and high dispersibility, and the average particle size is about 4-5 nm.

[0058] Figure 2 Mapping elemental distribution map and EDS energy spectrum analysis map of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1. It can be seen from the figure that the nanoparticles in the material have a morphology with uniformly distributed C, O, and Cu elements, indicating that the material has been successfully prepared.

[0059] Figure 3 XRD pattern of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1. It can be seen from the figure that the IA-Cu material presents a polycrystalline MOF structure, and the phase comparison through the diffraction lines also shows the successful preparation of IA-Cu.

[0060] Figure 4 Zeta potential analysis map of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1. It can be seen from the figure that the Zeta potentials of IA-Cu nanomaterials suspended in PBS (pH = 7.4) and high-glucose DMEM basal medium are -13.47 mV and -14.8 mV respectively, indicating that the nanomaterials have good physiological stability (the higher the charge density on the particle surface, the greater the Zeta potential, the greater the charge repulsion between particles, and the less likely to aggregate).

[0061] Figure 5 Fourier transform infrared spectroscopy (FT-IR) analysis map of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1. It can be seen from the figure that a broad and strong band is shown at about 3500 cm -1 which belongs to -OH, and the absorption bands at about 1704 and 1437 cm -1 shift to about 1600 and 1420 cm -1 respectively, proving the binding between Cu(II) and the carboxyl group in IA.

[0062] Figure 6 XPS pattern of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1. It can be seen from the figure that the Cu-2p peak splitting and Auger spectrum confirm the valence state of copper itaconate. According to the integrated area, the content of Cu 0 / Cu + is 86.57%, and the content of Cu 2+ is 13.43%, indicating that mainly low-valent copper ions exist on the surface of copper itaconate (IA-Cu).

[0063] Figure 7TG curve of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1. It can be seen from the figure that the content of itaconic acid in the copper itaconate nanoparticles accounts for 47.63% of the total mass of the material, and the copper ions account for 52.37%.

[0064] Figure 8 Test results of electron spin resonance (ESR) of the reaction scavenging system of itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 1 with hydroxyl radicals. It can be seen from the figure that this nanomaterial can scavenge hydroxyl radicals, and there is a positive correlation with the applied concentration.

[0065] Figure 9 TEM image of the itaconic acid-based MOF material prepared in Comparative Example 1. It can be seen from the figure that the IA-Cu material prepared under this condition has too large particles, poor dispersibility, and agglomerates together.

[0066] Figure 10 TEM image of the itaconic acid-based MOF material prepared in Comparative Example 2. It can be seen from the figure that the IA-Cu material prepared under this condition has too large particles, poor dispersibility, and agglomerates together.

[0067] Figure 11 TEM image of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 2. It can be seen from the figure that the IA-Cu material prepared under this condition has uniform particle morphology, uniform size, and good dispersibility.

[0068] Figure 12 TEM image of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 3. It can be seen from the figure that the material particles have uniform morphology, uniform size, and good dispersibility.

[0069] Figure 13 TEM image of the itaconic acid-copper metal-organic framework nanomaterial (IA-Cu) prepared in Example 4. It can be seen from the figure that the obtained IA-Cu material particles have uniform morphology, uniform size, and good dispersibility.

[0070] Figure 14 TEM image of the itaconic acid-based MOF material prepared in Comparative Example 3. It can be seen from the figure that the material particle morphology is not uniform and the size is not uniform.

[0071] Figure 15 TEM image of the itaconic acid-based MOF material prepared in Comparative Example 4. It can be seen from the figure that the material has no particle morphology, poor dispersibility, and agglomerates together.

[0072] Figure 16TEM image of the itaconic acid-based MOF material prepared in Comparative Example 5. It can be seen from the figure that the morphology of the material particles is non-uniform and the size is uneven.

Claims

1. A carboxylic acid ligand-copper metal-organic framework nanomaterial, characterized in that, The carboxylic acid ligand-copper metal-organic framework nanomaterial is a MOF structure with polycrystals formed by connecting carboxylic acid ligands and copper ions through coordination bonds; The carboxylic acid ligand includes at least one of dicarboxylic acid and tricarboxylic acid; preferably, the dicarboxylic acid includes at least one of itaconic acid and fumaric acid, and the tricarboxylic acid includes at least one of aconitic acid and citric acid; The valence states of the copper ions include 0, +1, and +2; preferably, based on the total amount of copper ions being 100 at%, the total content of Cu 0 , Cu + is 85 to 90 at%, and the content of Cu 2+ is 10 to 15 at%.

2. The carboxylic acid ligand-copper metal-organic framework nanomaterial according to claim 1, characterized in that, In the carboxylic acid ligand-copper metal-organic framework nanomaterial, the mass ratio of the carboxylic acid ligand is 47-88 wt%, preferably 86-88 wt%, and the mass ratio of copper is 12-53 wt%, preferably 12-14 wt%.

3. The carboxylic acid ligand-copper metal-organic framework nanomaterial according to claim 1 or 2, characterized in that The carboxylic acid ligand-copper metal-organic framework nanomaterial has a spherical morphology with an average particle size of 4-5 nm.

4. A method for preparing the carboxylic acid ligand-copper metal-organic framework nanomaterial according to any one of claims 1-3, characterized in that, The preparation method includes the following steps: adding a copper salt solution to a carboxylic acid ligand solution and mixing, while maintaining condensation reflux; then, after washing and drying, the carboxylic acid ligand-copper metal-organic framework nanomaterial is obtained.

5. The preparation method according to claim 4, characterized in that, The copper salt is at least one of anhydrous copper acetate, copper acetate monohydrate, copper acetate dihydrate, copper hydroxide, and copper chloride; wherein, the concentration of the copper salt solution is 5-25 mg / mL, preferably 5-20 mg / mL; The concentration of the carboxylic acid ligand solution is 5-20 mg / mL, preferably 10-15 mg / mL; The molar ratio of the carboxylic acid ligand to the copper salt is 1.5:(1-3), preferably 1.5:(1.5-3), more preferably 1.5:(2-3), and most preferably 1.5:2.

5.

6. The preparation method according to claim 4 or 5, characterized in that, The parameters of the condensation reflux include: rotation speed 300-400 rpm, temperature 110-125 °C, and time 4-5 h.

7. The preparation method according to any one of claims 4-6, characterized in that, The drying method is vacuum freeze-drying, the temperature is -90 to -70 °C, and the time is 6-12 h.

8. An injection of a carboxylic acid ligand-copper metal-organic framework nanomaterial, characterized in that, The injection of the carboxylic acid ligand-copper metal-organic framework nanomaterial includes: a biocompatible solution, and the carboxylic acid ligand-copper metal-organic framework nanomaterial according to any one of claims 1-3 dispersed in the biocompatible solution.

9. The carboxylic acid ligand - copper metal - organic framework nanomaterial injection according to claim 8, characterized in that, The biocompatible solution includes at least one of normal saline and phosphate buffer solution.

10. The carboxylic acid ligand - copper metal - organic framework nanomaterial injection according to claim 8 or 9, characterized in that, The concentration of the carboxylic acid ligand-copper metal-organic framework nanomaterial in the injection is 10-30 mg / mL.

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