Nano MOF (Metal Organic Framework) drug loading platform for synchronously realizing loading and modification as well as preparation method and application of nano MOF drug loading platform

Abstract

The invention provides a nano MOF (Metal Organic Framework) drug loading platform for synchronously realizing loading and modification as well as a preparation method and application thereof, and belongs to the field of drug loading. The method comprises the following steps: dissolving a pesticide to be loaded in an organic solvent, then adding beta-cyclodextrin, and stirring until the beta-cyclodextrin is completely dissolved to obtain a mixed solution; and dispersing the activated UiO-66-NH2 in the mixed solution, sequentially adding a condensing agent and a catalyst in a certain proportion, stirring at room temperature, centrifugally collecting precipitate, washing, and drying in vacuum to obtain the drug loading platform. According to the invention, the characteristics of porosity, adsorption and easy surface modification of the MOFs material are utilized, the properties of the MOFs and the encapsulating material are combined, and the esterification reaction principle is utilized, so that pesticide loading and encapsulating modification are synchronously carried out, the preparation time is saved, and the control effect of the bactericide on crop diseases is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of drug loading, and in particular to a nano MOF drug loading platform capable of simultaneously realizing loading and modification, and a preparation method and application thereof. Background Art

[0002] Pesticides are an effective means of preventing and controlling agricultural pests and diseases. Nanomaterials have broad application prospects in the field of pesticide formulation processing due to their small size, high specific surface area, and high reactivity, and are effective carriers for pesticide delivery. Pesticide nanomaterials are conducive to improving the stability and dispersibility of pesticide active ingredients, ensuring the effectiveness of pesticides, and improving the adhesion and permeability of pesticides on the surface of biological targets. Depending on the properties of nanocarriers or surface modification functions, the intelligent release of pesticide active ingredients can be achieved.

[0003] MOFs (metal organic frameworks), a representative of organic-inorganic hybrid materials, are a representative type of pesticide active ingredient delivery carrier. MOFs (metal organic frameworks), also known as porous coordination polymers, are a type of porous material formed by self-assembly of metal ions or clusters and organic ligands through coordination bonds. The reason why MOFs can be used as a promising type of nano-sized drug delivery carrier is mainly due to their excellent physical and chemical properties, including: (1) extremely large specific surface area and extremely high pore volume; (2) easily modified surface, which can regulate the physical and chemical properties of the pore surface; (3) adjustable spatial structure, which can effectively control the pore size. In addition, due to the diversity of ions and ligands, MOFs have different stabilities under different environmental conditions (such as water, pH), which gives MOFs the possibility of drug release in response to environmental stimuli. At present, constructing a drug-loaded MOFs system generally requires two steps: first, the effective loading of drugs on MOFs is achieved through physical adsorption or encapsulation of MOFs. Considering the differences in the pore sizes of different MOFs, achieving effective loading of drugs on MOFs generally requires synthesizing MOFs first and then loading drugs, or adding drugs during the preparation of MOFs. The latter is generally based on the consideration that the pore size of MOFs is too small. Secondly, according to the physical and chemical properties of the MOFs surface (such as functional groups), the surface modification of MOFs is achieved by introducing shells that respond to different environmental / biological stimuli, that is, wrapping one or more layers of shells on the surface of MOFs.

[0004] However, although the traditional method of constructing drug-loaded MOFs system can also achieve drug loading and drug sustained release functions, the traditional method has the defects that drug loading and surface modification need to be carried out step by step, the preparation process is complicated and time-consuming, the solvent consumption is large, and the carrier is easily lost during the preparation process. Summary of the invention

[0005] In view of this, the present invention provides a nano-MOF drug-carrying platform that realizes loading and modification simultaneously, and a preparation method and application thereof. The present invention utilizes the characteristics of MOFs materials, such as porosity, adsorption, and easy surface modification, combines the properties of MOFs and encapsulation materials used, and utilizes the principle of esterification reaction to realize simultaneous pesticide loading and encapsulation modification, thereby saving preparation time and improving the control effect of fungicides on crop diseases. The invention is original in the field of nano-MOFs pesticide preparation.

[0006] In order to achieve the above effects, the present invention adopts the following technical solutions:

[0007] The present invention provides a method for preparing a nano-MOF drug-carrying platform that realizes loading and modification simultaneously, comprising the following steps:

[0008] The pesticide to be loaded is dissolved in an organic solvent, and then β-cyclodextrin is added and stirred until it is completely dissolved to obtain a mixed solution; the activated UiO-66-NH2 is dispersed in the mixed solution, and then a certain proportion of a condensing agent and a catalyst are added in sequence, and after stirring at room temperature, the precipitate is collected by centrifugation, washed, and vacuum dried to obtain a drug loading platform.

[0009] Preferably, the organic solvent is selected from at least one of N,N-dimethylformamide, methanol and ethanol, and the pesticide includes but is not limited to carbendazim, azoxystrobin and pyraclostrobin.

[0010] Preferably, the condensing agent is selected from at least one of dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), the catalyst is selected from at least one of 4-methylaminopyridine (DMAP), 4-pyrrolidinopyridine (4-PPY), 1-hydroxybenzotriazole (HOBt), and the molar ratio of β-cyclodextrin, activated UiO-66-NH2, condensing agent and catalyst is 3.1:(0.5-1):206.3:122.17.

[0011] Preferably, the room temperature stirring time is 24h±10min, the vacuum drying is vacuum freeze drying, the vacuum freeze drying temperature is -55 to -45°C, and the time is 8-12h.

[0012] Preferably, the preparation method of activated UiO-66-NH2 comprises the following steps: using metal cation zirconium as a metal ligand, using 2-aminoterephthalic acid as an organic ligand, using N,N-dimethylformamide as an organic solvent, adding polyvinyl pyrrolidone, adopting a solvent thermal synthesis method to obtain UiO-66-NH2, and then thermally activating UiO-66-NH2 to obtain activated UiO-66-NH2.

[0013] Preferably, the preparation method of the activated UiO-66-NH2 comprises the following steps: Dissolve ZrCl4, 2-aminoterephthalic acid, and polyvinylpyrrolidone in N,N-dimethylformamide. After complete dissolution, add deionized water and stir evenly to obtain a mixed solution. Continuously heat the mixed solution in an environment of 150°C ± 1°C for 10 h ± 10 min, then cool it to room temperature, collect the precipitate by centrifugation, wash the precipitate with N,N-dimethylformamide and methanol in sequence, and after vacuum drying, obtain the activated UiO-66-NH2 through thermal activation.

[0014] Preferably, the temperature of the thermal activation is 100°C ± 1°C, and the time is 2 h ± 10 min.

[0015] Preferably, the molar ratio of ZrCl4, 2-aminoterephthalic acid, polyvinylpyrrolidone, N,N-dimethylformamide, and deionized water is 50:50:1:25000:1 - 50, and the temperature of the vacuum drying is 60 - 80°C.

[0016] The present invention also provides a nano-MOF drug-loading platform that simultaneously realizes loading and modification prepared by the above method, and the application of the nano-MOF drug-loading platform that simultaneously realizes loading and modification in the fields of pesticide loading and agricultural crop disease control.

[0017] Compared with the prior art, the present invention has the following beneficial effects: The present invention improves and optimizes the traditional construction strategy of drug-loading MOFs that first load and then modify, and proposes an integrated preparation strategy for drug loading of Zr-MOF and encapsulation of the drug-loading platform, which not only saves the preparation time but also improves the drug efficacy, helps to effectively control crop fungal diseases, and is original in the field of nano-MOF pesticide preparation. Description of the Drawings

[0018] Figure 1 It is a scanning electron microscope (SEM) image of UiO-66-NH2 prepared in Example 1 of the present invention.

[0019] Figure 2 It is the dispersibility of UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1 of the present invention in aqueous solution.

[0020] Figure 3 It is the in vitro antibacterial experiment effect diagram of UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1 of the present invention.

[0021] Figure 4 It is the statistical chart of the colony diameter of Colletotrichum gloeosporioides of UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1 of the present invention.

[0022] Figure 5It is the effect diagram of preventing and controlling anthracnose by spraying UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1 of the present invention on the leaf surface of corn leaves.

[0023] Figure 6 It is the statistical chart of the control efficiency of corn anthracnose after spraying UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1 of the present invention on the leaf surface of corn leaves.

[0024] Figure 7 It is the effect diagram of the in vitro antibacterial experiment of UiO-66-NH2@Miyin@β-cyclodextrin and UiO-66-NH2@Pizuo@β-cyclodextrin prepared in Example 2 and Example 3 of the present invention.

[0025] Figure 8 It is the statistical chart of the colony diameter of anthracnose bacteria of UiO-66-NH2@Miyin@β-cyclodextrin and UiO-66-NH2@Pizuo@β-cyclodextrin prepared in Example 2 and Example 3 of the present invention. Detailed implementation manners

[0026] In some embodiments, the present invention provides a preparation method of a nano MOF drug delivery platform for synchronously realizing loading and modification, including the following steps:

[0027] Dissolve the pesticide to be loaded in an organic solvent, then add β-cyclodextrin and stir until completely dissolved to obtain a mixed solution; disperse the activated UiO-66-NH2 in the mixed solution, and then sequentially add a certain proportion of a condensing agent and a catalyst, stir at room temperature, centrifuge to collect the precipitate, wash, and dry in vacuum to obtain a drug delivery platform, denoted as UiO-NH2@Duojun@β-cyclodextrin.

[0028] The particle size of the UiO-NH2@Duojun@β-cyclodextrin is 100-500 nm, preferably 200 nm.

[0029] In the process of β-cyclodextrin encapsulation, the present invention utilizes the Steglich esterification reaction, uses DCC as a condensing agent and DMAP as a catalyst to promote the esterification reaction between the carboxyl group (-COOH) in UiO-66-NH2 and the hydroxyl group (-OH) of β-cyclodextrin. An integrated strategy for drug loading and drug delivery platform encapsulation is realized, which helps to improve the effective control of crop fungal diseases.

[0030] In some embodiments, the organic solvent is selected from at least one of N,N-dimethylformamide, methanol, and ethanol. Preferably, the organic solvent is N,N-dimethylformamide; the pesticides include but are not limited to carbendazim, azoxystrobin, and pyraclostrobin.

[0031] In some embodiments, the condensing agent is selected from at least one of dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), preferably, the condensing agent is dicyclohexylcarbodiimide; the catalyst is selected from at least one of 4-methylaminopyridine (DMAP), 4-pyrrolidinopyridine (4-PPY), 1-hydroxybenzotriazole (HOBt), preferably, the catalyst is 4-methylaminopyridine; the molar ratio of β-cyclodextrin, activated UiO-66-NH2, condensing agent and catalyst is 3.1:(0.5-1):206.3:122.17.

[0032] In some embodiments, the room temperature stirring time is 24h±10min, preferably, the room temperature stirring time is 24h; the vacuum drying is vacuum freeze drying, the vacuum freeze drying temperature is -55 to -45°C, and the time is 8-12h.

[0033] In some embodiments, the preparation method of activated UiO-66-NH2 comprises the following steps: using metal cation zirconium as a metal ligand, using 2-aminoterephthalic acid as an organic ligand, using N,N-dimethylformamide as an organic solvent, adding polyvinyl pyrrolidone, and obtaining UiO-66-NH2 by a solvent thermal synthesis method, and then thermally activating UiO-66-NH2 to obtain activated UiO-66-NH2.

[0034] In some embodiments, the preparation method of the activated UiO-66-NH2 comprises the following steps: dissolving ZrCl4, 2-aminoterephthalic acid, and polyvinyl pyrrolidone in N,N-dimethylformamide; after complete dissolution, adding deionized water and stirring evenly to obtain a mixed solution; continuously heating the mixed solution at 150°C±1°C for 10h±10min; then cooling the mixed solution to room temperature; collecting the precipitate by centrifugation; washing the precipitate with N,N-dimethylformamide and methanol in turn; and obtaining activated UiO-66-NH2 after vacuum drying and thermal activation.

[0035] In some embodiments, the thermal activation temperature is 100°C±1°C, and the time is 2h±10min. Preferably, the thermal activation temperature is 100°C, and the time is 2h.

[0036] In some embodiments, the molar ratio of ZrCl4, 2-aminoterephthalic acid, polyvinyl pyrrolidone, N,N-dimethylformamide and deionized water is 50:50:1:25000:(1-50). Preferably, the molar ratio of ZrCl4, 2-aminoterephthalic acid, polyvinyl pyrrolidone, N,N-dimethylformamide and deionized water is 50:50:1:25000:25.

[0037] In some embodiments, the vacuum freeze drying is carried out at a temperature of -55 to -45°C and for a time of 8 to 12 hours.

[0038] The MOFs material UiO-66-NH2 selected in the present invention is a MOFs (Zr-MOF) with extremely strong chemical stability formed by high-valent metal cation zirconium (Zr, +4) as a metal ligand and an organic ligand 2-aminoterephthalic acid (NH2-BDC). It can maintain good structural stability under different pH conditions.

[0039] In the process of preparing nano-scale UiO-66-NH2, the present invention additionally introduces high molecular weight polymer polyvinyl pyrrolidone (PVP) to make UiO-66-NH2 also obtain good dispersibility in aqueous solution, making it a nano water dispersant. The nano MOFs drug-carrying platform loaded with commonly used pesticides can be used as a dispersant in the field of pesticides, that is, it can effectively improve the dispersibility of pesticides in water, and when used as foliar spraying, it has a better control effect than conventional commercial pesticide wettable powders such as commercial carbendazim wettable powders.

[0040] While loading the drug, the present invention introduces the bio-nontoxic and biocompatible high molecular polymer β-cyclodextrin to modify the surface of the drug-loaded MOFs, and utilizes the characteristic of Zr-MOF responding to different pH stimulations in the environment to achieve the sustained release of pesticides and reduce the environmental risks that may be caused by pesticides.

[0041] In some embodiments, the present invention also provides a nano-MOF drug delivery platform that achieves simultaneous loading and modification prepared by the method, as well as the application of the nano-MOF drug delivery platform that achieves simultaneous loading and modification in the fields of pesticide loading and agricultural crop disease prevention and control.

[0042] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention.

[0043] The experimental methods or test methods described in the following examples are conventional methods unless otherwise specified; the raw materials and auxiliary agents are obtained from conventional commercial channels or prepared by conventional methods unless otherwise specified. The strains used in the present invention can be purchased from conventional commercial strain collection institutions.

[0044] The specific steps of the in vitro antibacterial experiment involved in the present invention are:

[0045] (1) First, prepare 100 ml of PDA (potato dextrose agar) medium, sterilize it at 120°C and autoclave for 20 min, then cool it to 45-50°C for later use;

[0046] (2) Ultrasonic dispersion of UiO-66-NH2@multibacteria@β-ring in an appropriate amount of sterile water, and add it to PDA culture medium to make the final concentration of UiO-66-NH2@multibacteria@β-ring 2.5ppm, shake evenly, and pour into a 9cm culture dish, cool for several hours until the culture medium solidifies;

[0047] (3) Use a cork puncher to take a 5 mm diameter anthrax colony that has been cultured for 7 days and place it in the center of the solidified PDA culture medium. After sealing with a sealing film, culture it in a constant temperature incubator at 25°C. On the 7th day, the colony diameter is measured using the cross method.

[0048] The inhibition rate was calculated by the following formula: inhibition rate % = (colony diameter of the treated group on the 7th day - initial colony diameter) / colony diameter of the control group on the 7th day * 100%.

[0049] Example 1

[0050] A method for preparing a nano-MOF drug delivery platform that simultaneously realizes loading and modification, the specific steps are as follows:

[0051] (1) Preparation of UiO-66-NH2

[0052] Dissolve ZrCl4 (602 mg, 2.6 mmol), NH2-BDC (468 mg, 2.6 mmol), and PVP (517 mg, 0.052 mmol) in 300 ml of N,N-dimethylformamide (DMF) organic solvent, the molar ratio of ZrCl4, NH2-BDC, and PVP being 1:1:2. After complete dissolution, add 140 μl of deionized water and stir evenly to obtain a mixed solution; place the mixed solution in a high-temperature and high-pressure reactor, and heat it at 150°C for 10 h; cool to room temperature, collect the precipitate by centrifugation, wash the precipitate with DMF and MeOH (methanol) for multiple times, and obtain UiO-66-NH2 after vacuum drying at 60°C; activate UiO-66-NH2 at 100°C for 2 h before use to obtain activated UiO-66-NH2;

[0053] (2) Drug loading of UiO-66-NH2 and simultaneous encapsulation of β-cyclodextrin shell

[0054] 120 mg of the pesticide carbendazim (AR grade) to be loaded was completely dissolved in 30 ml of DMF solution by ultrasonication, and then β-cyclodextrin (600 mg, 0.529 mmol) was added and stirred until it was completely dissolved to obtain a mixed solution;

[0055] The activated UiO-66-NH2 (300 mg, 0.171 mmol) was ultrasonically dispersed in the mixed solution, and then dicyclohexylcarbodiimide (1230 mg, 0.006 mmol) and 4-methylaminopyridine (360 mg, 0.003 mmol) were added successively. Under room temperature conditions, stirring was continued for 24 h, and the precipitate was collected by centrifugation. The precipitate was washed successively with absolute ethanol and deionized water, and then vacuum freeze-dried at -55 to -45 °C for 8 - 12 h to obtain a drug-loading platform, denoted as UiO-NH2@Duojun@β-cyclodextrin.

[0056] Test examples:

[0057] 1) The UiO-66-NH2 prepared in Example 1 was characterized by scanning electron microscopy, and the obtained scanning electron micrograph is as Figure 1 shown. It can be seen that the particle size of the MOF material UiO-66-NH2 prepared in Example 1 is about 100 nm, indicating that the nano-scale MOF material UiO-66-NH2 was successfully prepared in this invention.

[0058] 2) The UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1 was placed in water. After standing for 30 min, the dispersibility of UiO-66-NH2@Duojun@β-cyclodextrin in water is as Figure 2 shown. It can be seen that UiO-66-NH2@Duojun@β-cyclodextrin can maintain good dispersibility in aqueous solution.

[0059] 3) An in vitro antibacterial experiment was carried out on the UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1. The results are as Figure 3 and Figure 4 shown. Figure 3 In the left figure of , it is the blank control group (CK) without adding any antibacterial agent, in the middle is the experimental group with 0.25 ai ppm (ai ppm, that is, the concentration of the effective fungicide component is 0.25 ppm) UiO-66-NH2@Duojun@β-cyclodextrin (denoted as T1), and in the right figure is the control experimental group with carbendazim technical (concentration 0.25 ppm) (denoted as T2). Figure 3 What was tested was the inhibitory effect of UiO-66-NH2@Duojun@β-cyclodextrin on the plant pathogenic fungus Colletotrichum graminicola. Figure 4 What is shown is the statistics of the colony diameter of Colletotrichum graminicola based on the in vitro antibacterial experiment. From Figure 3 and Figure 4 it can be known that the UiO-66-NH2@Duojun@β-cyclodextrin prepared in Example 1 has an obvious inhibitory effect on the growth of the pathogenic bacteria colony, and the inhibition rate exceeds 80%, and it is superior to the antibacterial effect of the carbendazim technical with the same dose.

[0060] 4) The UiO-66-NH2@carbendazim@β-cyclodextrin prepared in Example 1 was sprayed on the leaves of corn, and its control effect on Colletotrichum graminicola was tested. The results are as Figure 5 and Figure 6 shown. Figure 5 In the left figure in the middle, it is the blank control group without adding any bacteriostatic agent (denoted as CK). In the middle, it is the experimental group adding 2.5 ppm (the effective carbendazim concentration is 0.25 ppm) of UiO-66-NH2@carbendazim@β-cyclodextrin (denoted as T1). In the right figure, it is the control experimental group adding carbendazim powder (concentration 0.25 ppm) (denoted as T2).

[0061] It can be Figure 5 seen that spraying UiO-66-NH2@carbendazim@β-cyclodextrin on the leaves can effectively inhibit the infection of Colletotrichum graminicola, and the lesion area is smaller than that of commercial carbendazim fungicide. It shows that UiO-66-NH2@carbendazim@β-cyclodextrin has a good inhibitory effect on diseases.

[0062] Figure 6 The following is the statistical result of the control efficiency of Colletotrichum graminicola after spraying the UiO-66-NH2@carbendazim@β-cyclodextrin prepared in Example 1 on the leaves of corn. It can be Figure 6 seen that compared with ordinary commercial fungicides, the control effect of UiO-66-NH2@carbendazim@β-cyclodextrin prepared in Example 1 on crop diseases has increased by about 50%.

[0063] Example 2

[0064] (1) Preparation of UiO-66-NH2

[0065] ZrCl4 (602 mg, 2.6 mmol), NH2-BDC (468 mg, 2.6 mmol), and PVP (517 mg, 0.052 mmol) were dissolved in 300 ml of N,N-dimethylformamide (DMF) organic solvent. The molar ratio of ZrCl4, NH2-BDC, and PVP was 1:1:2. After complete dissolution, 140 μl of deionized water was added and stirred evenly to obtain a mixed solution. The mixed solution was placed in a high-temperature and high-pressure reaction kettle and continuously heated at 150 °C for 10 h. After cooling to room temperature, the precipitate was collected by centrifugation, and the precipitate was washed repeatedly with DMF and MeOH (methanol). After vacuum drying at 60 °C, UiO-66-NH2 was obtained. Before use, UiO-66-NH2 was activated at 100 °C for 2 h to obtain activated UiO-66-NH2;

[0066] (2) Drug loading of UiO-66-NH2 and synchronous encapsulation of β-cyclodextrin shell

[0067] 750 mg of the pesticide azoxystrobin (AR grade) to be loaded was completely dissolved in 30 ml of DMF solution by ultrasonication, and then β-cyclodextrin (600 mg, 0.529 mmol) was added and stirred until it was completely dissolved to obtain a mixed solution;

[0068] Activated UiO-66-NH2 (180 mg, 0.103 mmol) was ultrasonically dispersed in the mixed solution, and dicyclohexylcarbodiimide (1230 mg, 0.006 mmol) and 4-methylaminopyridine (360 mg, 0.003 mmol) were added in sequence. The mixture was stirred for 24 h at room temperature, and the precipitate was collected by centrifugation. The precipitate was washed with anhydrous ethanol and deionized water successively, and the precipitate was freeze-dried in vacuum at -55 to -45 ° C for 8-12 h to obtain a drug loading platform, which was recorded as UiO-66-NH2@Pyrimidine@β-ring.

[0069] Example 3

[0070] (1) Preparation of UiO-66-NH2

[0071] Dissolve ZrCl4 (602 mg, 2.6 mmol), NH2-BDC (468 mg, 2.6 mmol), and PVP (517 mg, 0.052 mmol) in 300 ml of N,N-dimethylformamide (DMF) organic solvent, the molar ratio of ZrCl4, NH2-BDC, and PVP being 1:1:2. After complete dissolution, add 140 μl of deionized water and stir evenly to obtain a mixed solution; place the mixed solution in a high-temperature and high-pressure reactor, and heat it at 150°C for 10 h; cool to room temperature, collect the precipitate by centrifugation, wash the precipitate with DMF and MeOH (methanol) for multiple times, and obtain UiO-66-NH2 after vacuum drying at 60°C; activate UiO-66-NH2 at 100°C for 2 h before use to obtain activated UiO-66-NH2;

[0072] (2) Drug loading of UiO-66-NH2 and simultaneous encapsulation of β-cyclodextrin shell

[0073] 750 mg of the pesticide pyraclostrobin (AR grade) to be loaded was completely dissolved in 30 ml of DMF solution by ultrasonication, and then β-cyclodextrin (600 mg, 0.529 mmol) was added and stirred until it was completely dissolved to obtain a mixed solution;

[0074] Activated UiO-66-NH2 (180 mg, 0.103 mmol) was ultrasonically dispersed in the mixed solution, and then dicyclohexylcarbodiimide (1230 mg, 0.006 mmol) and 4-methylaminopyridine (360 mg, 0.003 mmol) were added in sequence. Stirring was continued for 24 h at room temperature, and the precipitate was collected by centrifugation. The precipitate was washed with anhydrous ethanol and deionized water successively, and vacuum freeze-dried at -55 to -45 ° C for 8-12 h to obtain a drug-loading platform, which was recorded as UiO-66-NH2@pyridine@β ring.

[0075] The UiO-66-NH2@pyrimidine@β ring and UiO-66-NH2@pyridine@β ring prepared in Example 2 and Example 3 were subjected to in vitro antibacterial experiments. Figure 7 and Figure 8 As shown, Figure 7 The left picture shows the blank control group (CK) without adding any antibacterial agent, the middle picture shows the antibacterial effect of UiO-66-NH2@Pyrimidine@β-ring, and the right picture shows the antibacterial effect of UiO-66-NH2@Pyridine@β-ring. Figure 7 and Figure 8 It can be seen that the UiO-66-NH2@pyrimidine@β ring and UiO-66-NH2@pyridine@β ring prepared in Example 2 and Example 3 have a significant inhibitory effect on the growth of corn anthracnose colonies.

[0076] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a nano-MOF drug-carrying platform that simultaneously realizes loading and modification, characterized in that: The following steps are involved: The pesticide to be loaded is dissolved in an organic solvent, and then β-cyclodextrin is added and stirred until it is completely dissolved to obtain a mixed solution; the activated UiO-66-NH2 is dispersed in the mixed solution, and then a certain proportion of a condensing agent and a catalyst are added in sequence, and after stirring at room temperature, the precipitate is collected by centrifugation, washed, and vacuum dried to obtain a drug loading platform.

2. The method for preparing a nano-MOF drug delivery platform for simultaneous loading and modification according to claim 1, characterized in that: The organic solvent is at least one of N,N-dimethylformamide, methanol and ethanol.

3. The method for preparing a nano-MOF drug delivery platform for simultaneous loading and modification according to claim 1, characterized in that: The condensing agent is selected from at least one of dicyclohexylcarbodiimide, diisopropylcarbodiimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, the catalyst is selected from at least one of 4-methylaminopyridine, 4-pyrrolidinopyridine and 1-hydroxybenzotriazole, and the molar ratio of β-cyclodextrin, activated UiO-66-NH2, condensing agent and catalyst is 3.1:(0.5-1):206.3:122.

17.

4. The method for preparing a nano-MOF drug delivery platform that realizes simultaneous loading and modification according to claim 1, characterized in that: The room temperature stirring time is 24h±10min, the vacuum drying is vacuum freeze drying, the vacuum freeze drying temperature is -55 to -45°C, and the time is 8-12h.

5. The method for preparing a nano-MOF drug delivery platform that realizes simultaneous loading and modification according to claim 1, characterized in that: The preparation method of activated UiO-66-NH2 comprises the following steps: using metal cation zirconium as a metal ligand, using 2-aminoterephthalic acid as an organic ligand, using N,N-dimethylformamide as an organic solvent, adding polyvinyl pyrrolidone, adopting a solvent thermal synthesis method to obtain UiO-66-NH2, and then thermally activating UiO-66-NH2 to obtain activated UiO-66-NH2.

6. The method for preparing a nano-MOF drug delivery platform that realizes simultaneous loading and modification according to claim 1, characterized in that: The preparation method of the activated UiO-66-NH2 comprises the following steps: dissolving ZrCl4, 2-aminoterephthalic acid and polyvinyl pyrrolidone in N,N-dimethylformamide, adding deionized water and stirring evenly after the dissolution is complete to obtain a mixed solution, continuously heating for 10h±10min in an environment of 150°C±1°C, then cooling to room temperature, collecting a precipitate by centrifugation, washing the precipitate with N,N-dimethylformamide and methanol in turn, vacuum drying, and performing thermal activation to obtain activated UiO-66-NH2.

7. The method for preparing a nano-MOF drug-carrying platform capable of simultaneous loading and modification according to any one of claims 5 or 6, characterized in that: The temperature of the thermal activation is 100°C±1°C, and the time is 2h±10min.

8. The method for preparing a nano-MOF drug delivery platform that realizes simultaneous loading and modification according to claim 6, characterized in that: The molar ratio of ZrCl4, 2-aminoterephthalic acid, polyvinyl pyrrolidone, N,N-dimethylformamide and deionized water is 50:50:1:25000:1-50, and the vacuum drying temperature is 60-80°C.

9. A nano-MOF drug delivery platform that achieves simultaneous loading and modification, prepared according to the method of any one of claims 1 to 8.

10. Application of the nano-MOF drug-carrying platform prepared according to the method of any one of claims 1 to 8 or the nano-MOF drug-carrying platform according to claim 9 in the fields of pesticide loading and agricultural crop disease prevention and control.

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