A preparation method of a cell membrane-coated nanodelivery platform

Abstract

The application provides a preparation method of a cell membrane coated nanometer drug delivery platform and belongs to the technical field of drug delivery systems. The prepared NH2-MIL-88B(Fe)-MG132 material is used as a drug carrier to construct a cell membrane coated nanometer drug delivery platform, so that the targeted chemical dynamic therapy and the epigenetic regulation combined treatment effect are achieved. The drug delivery platform constructed by the application has the advantages of high targeting and low toxic side effects, reduces the phagocytosis of macrophages before the concentration in the tumor microenvironment, plays a certain role in activating the body and tumor related immune activity, and even achieves the effect of immunogenic site death of tumor cells. The drug delivery platform has high targeting and specificity, no drug burst release, high water solution stability, and higher aggregation in the tumor site.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of drug delivery systems, in particular to a preparation method of a cell membrane-coated nano drug delivery platform. BACKGROUND

[0002] Colorectal cancer is the most common malignant tumor of the digestive tract worldwide, and has a high metastatic rate. At present, the treatment methods for metastatic colorectal cancer (mCRC) in clinical practice include surgical resection, radiotherapy, chemotherapy, targeted therapy and other methods. In order to improve the clinical treatment effect of mCRC patients, the follow-up antitumor drug treatment of such patients is particularly important. Transcriptional epigenetic modification, including DNA methylation in cells, covalent modification of histones (such as acetylation, methylation, ubiquitination, phosphorylation, etc.) and chromatin rearrangement, has been considered to be related to many biological activities. Abnormal epigenetic regulation is considered to be related to the early stage and progression of cancer, which also makes tumors difficult to treat and resistant to conventional treatment methods. The ubiquitin-proteasome system (UPS) plays a crucial role in maintaining cellular homeostasis, regulating cell proliferation, differentiation, cycle and apoptosis, etc. Related studies have shown that the ubiquitination pathway and the development and metastasis of various malignant tumors (lung cancer, hematological tumors, colorectal cancer, etc.) are closely related. Among them, single drug therapy inhibits the growth and metastasis of colorectal malignant tumors, or exerts a synergistic antitumor effect through the ubiquitination pathway. On the other hand, in terms of the mechanism of action of anticancer drugs, the pathway control of the ubiquitination pathway has also become a major research direction. How to effectively control the occurrence of protein ubiquitination degradation to achieve the purpose of killing cancer cells or synergistically enhancing the antitumor effect has become a problem that biologists, medical scientists and others are trying to solve. It is disappointing that epigenetic regulation, which directly determines tumor progression, evolution and metastasis, is still rarely concerned.

[0003] With the development of material synthesis technology and biomedicine technology, the application and development of nanometer drug delivery system can improve the effectiveness of antitumor drugs. MOF is a kind of porous material with good stability and high specific surface area, which has been widely studied in the field of biomedicine in recent years. Certain metal ions or metal clusters are connected with specific organic ligands by strong coordination bonds to form metal organic frameworks with certain regularity. Because it contains both organic molecules and inorganic metals, metal organic frameworks have the dual characteristics of organic and inorganic materials. The feasibility study of MOF as a drug delivery system shows that MOF has high drug loading capacity and strong drug controlled release ability. NH2-MIL-88B(Fe) framework material is synthesized by metal Fe and organic ligand, which is a solid porous material with uniform crystal size. Due to its appropriate specific surface area porosity, good mechanical stability, adjustable surface characteristics, and strong metal-nitrogen bond, NH2-MIL-88B(Fe) metal organic framework material is considered as a potential drug delivery carrier in the field of drug delivery due to its low toxicity, high biocompatibility and high chemical stability under physiological conditions. This kind of nanomaterial has become a promising drug delivery carrier because of its spatial structure and surface modification to increase the affinity to bioactive molecules. NH2-MIL-88B(Fe) does not have additional chemical dynamic therapy sensitizers, and after using the iron active center, it has been determined as an excellent drug carrier and chemical dynamic therapy execution agent. Because the Fe active center in NH2-MIL-88B(Fe) will produce a Fenton-like reaction with the relatively high concentration of H2O2 in the tumor, too many hydroxyl radicals (·OH) are produced, resulting in an imbalance in the level of oxidative stress in the tumor microenvironment. Using NH2-MIL-88B(Fe) as a carrier to transport proteasome inhibitors can not only solve the problem of burst release of drugs in the body, but also better target tumor lesions, including primary lesions and metastatic lesions. Traditional anticancer drugs and treatment methods often "enemy and me" in the process of antitumor therapy, killing tumor cells while also killing normal cells, causing great harm to normal organs and tissues of the human body. Compared with the previous research on the epigenetic regulation of malignant tumors by single drugs, MOF-carrying proteasome inhibitor combination therapy generally significantly improves the treatment effect. However, the nanomaterial delivery platform needs to be further improved in terms of targeting, specific recognition and immune escape function. SUMMARY

[0004] Therefore, the application provides a preparation method of a cell membrane coated nanometer drug delivery platform, which has the advantages of strong targeting and low toxicity and side effects, reduces the phagocytosis of macrophages before concentration in the tumor microenvironment, activates the body and tumor-related immune activity to some extent, and even achieves the effect of immunogenic site death of tumor cells.

[0005] The application provides a preparation method of a cell membrane-coated nanodelivery platform.

[0006] S1, synthesis of NH2-MIL-88B(Fe):

[0007] S1-1, FeCl3·6H2O and F127 are added to deionized water and fully stirred, and mixed uniformly at room temperature for 2 h to obtain a mixed solution A;

[0008] S1-2, acetic acid is added to the mixed solution A in step S1-1 at a speed of 10-15 drops / min, and mixed for 1-1.5 h to obtain a mixed solution B;

[0009] S1-3, the mixed solution B prepared in step S1-2 is mixed with 2-amino terephthalic acid, and then reacted, and after the reaction is completed, the product is washed with water to remove excess reactants and surfactant F127, to obtain the NH2-MIL-88B(Fe); the amount of water used in the washing process is 5-10 times the volume of the product;

[0010] S2, synthesis of NH2-MIL-88B(Fe)-MG132:

[0011] The NH2-MIL-88B(Fe) prepared in step S1 is vacuum dried to obtain NH2-MIL-88B(Fe) powder, which is then mixed with proteasome inhibitor MG132 in dimethyl sulfoxide, and fully stirred at room temperature for 24 h to obtain the NH2-MIL-88B(Fe)-MG132;

[0012] S3, synthesis of a cell membrane-coated nanodelivery platform:

[0013] S3-1, PMSF is added to RIPA lysis buffer to obtain a mixed solution, the mixed solution is added to cells, and the cells are lysed on ice for 30 minutes; the cells are extruded at a constant speed for 30-50 times by using a glass extruder to break the cells under high pressure until 70%-90% of the cells are broken under a microscope, to obtain a cell membrane solution; the RIPA lysis buffer used in the embodiment of the application is RIPA lysis buffer (China) produced by Biyun Tian, product number P0013C;

[0014] S3-2, the NH2-MIL-88B(Fe)-MG132 prepared in step S2 is added to the cell membrane solution in step S3-1 and vortexed to mix, and then extruded 15 times by using a liposome extruder, to obtain the cell membrane-coated nanodelivery platform NH2-MIL-88B(Fe)-MG132@M.

[0015] Preferably, the mass ratio of FeCl3·6H2O and F127 in step S1-1 is 0.75-1.00.

[0016] Preferably, the concentration of FeCl3·6H2O in step S1-1 is 0.013-0.015 g / mL.

[0017] Preferably, the volume ratio of acetic acid to mixed solution A in step S1-2 is 0.4-0.7:23-30.

[0018] Preferably, the mass ratio of 2-amino terephthalic acid to FeCl3·6H2O added in step S1-3 is 1-1.5:3.

[0019] Preferably, the temperature of the reaction in step S1-3 is 100-120℃, and the time is 20-24h.

[0020] Preferably, the ratio of NH2-MIL-88B(Fe) powder to proteasome inhibitor MG132 to dimethyl sulfoxide in step S2 is 2-5 mg:200 μL:1800 μL in mass volume ratio, and the concentration of the proteasome inhibitor MG132 is 5 mg / mL.

[0021] Preferably, the concentration of benzylsulfonyl fluoride in the mixed solution in step S3-1 is 0.9-1 millimole / mL; and the ratio of the volume of the mixed solution to the number of cells is 0.9-1.1 ml:5*10 6 .

[0022] Preferably, the cells in step S3-1 are macrophages or tumor cells.

[0023] Preferably, the ratio of NH2-MIL-88B(Fe)-MG132 to cell solution in step S3-2 is 0.5-5 mg NH2-MIL-88B(Fe)-MG132 per 5*10 6 .

[0024] Compared with the prior art, the present application has the following beneficial effects:

[0025] The application provides a preparation method of a macrophage membrane coated nanometer drug delivery platform, uses NH2-MIL-88B(Fe)-MG132 material as a drug carrier, and achieves the combined treatment effect of targeted chemical dynamic therapy and epigenetic regulation. The drug delivery platform NH2-MIL-88B(Fe)-MG132@M has the advantages of strong targeting and low toxic side effects, not only reduces the phagocytosis of macrophages before concentration in the tumor microenvironment, but also plays a certain role in activating the immune activity of the body and tumor related immune activity, and even achieves the effect of immunogenic site death of tumor cells. Compared with common single drug treatment, the NH2-MIL-88B(Fe)-MG132@M drug delivery system has many unique advantages: high targeting and specificity, no drug burst release, good aqueous solution stability, higher aggregation in the tumor site, and the characteristics of in vivo drug monitoring and fluorescence imaging. The application constructs a cell membrane coated nanometer drug delivery platform with efficient combined treatment, which will promote the development of multi-level treatment and diagnosis nanometer platforms. The application adopts macrophage membrane targeting coating of metal organic framework nanometer material with the functions of chemical dynamic therapy and epigenetic regulation, the drug delivery platform has good dispersibility in water, good chemical catalytic property and fluorescence tracing characteristics, and can be used to enhance the targeting and specific recognition to realize the high efficient combined treatment effect. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 Figure 1 is a schematic diagram of the synthesis process of the cell membrane coated nanometer drug delivery platform in Example 1.

[0027] Figure 2 Figure 3 is a transmission electron microscope (TEM) diagram of NH2-MIL-88B(Fe).

[0028] Figure 3 Figure 5 is a transmission electron microscope (TEM) diagram of NH2-MIL-88B(Fe)-MG132@M) after phosphotungstic acid negative staining.

[0029] Figure 4 Figure 7 is a Zeta potential diagram of NH2-MIL-88B(Fe)-MG132 and NH2-MIL-88B(Fe)-MG132@M.

[0030] Figure 5 Figure 9 is an XPS diagram of NH2-MIL-88B(Fe).

[0031] Figure 6 Figure 11 is the result of observing the integrity of proteins on the cell membrane by using SDS-PAGE electrophoresis and coomassie blue staining.

[0032] Figure 7Results of drug release ability of NH2-MIL-88B(Fe)-MG132 and NH2-MIL-88B(Fe)-MG132@M drug delivery system.

[0033] Figure 8 Results of cell uptake of NH2-MIL-88B(Fe)-MG132.

[0034] Figure 9 Results of cell uptake of NH2-MIL-88B(Fe)-MG132@M.

[0035] Figure 10 Results of in vivo imaging of NH2-MIL-88B(Fe)-MG132 in mice at different time points.

[0036] Figure 11 Results of fluorescence quantification of in vivo imaging of NH2-MIL-88B(Fe)-MG132 at different time points.

[0037] Figure 12 Results of in vivo imaging of NH2-MIL-88B(Fe)-MG132@M in mice at different time points.

[0038] Figure 13 Photos of in vitro imaging of different tissues of mice after administration of NH2-MIL-88B(Fe)-MG132@M for 6h.

[0039] Figure 14 Results of fluorescence quantification of in vivo imaging of NH2-MIL-88B(Fe)-MG132@M at different time points.

[0040] Figure 15 Results of Calcein / PI cell viability and cytotoxicity detection of cells in different composite nanomaterial, drug or combined treatment groups after administration.

[0041] Figure 16 Results of Annexin V-FITC apoptosis detection of cells in different composite nanomaterial, drug or combined treatment groups after administration.

[0042] Figure 17 Changes in tumor volume of mice in different groups after injection for 14 days.

[0043] Figure 18 Changes in tumor weight of mice in different groups after injection for 14 days.

[0044] 1) MIL-88 represents NH2-MIL-88B(Fe); 2) MIL-88@M represents NH2-MIL-88B(Fe)@M; 3) MIL-88-MG132 represents NH2-MIL-88B(Fe)-MG132; 4) MIL-88-MG132@M represents NH2-MIL-88B(Fe)-MG132@M. DETAILED DESCRIPTION

[0045] The application is further described below in conjunction with examples.

[0046] Example 1

[0047] A preparation method of a cell membrane-coated nanodelivery platform, the steps being as follows:

[0048] S1, synthesis of NH2-MIL-88B(Fe):

[0049] S1-1, 0.36 g of FeCl3·6H2O and 0.32 g of F127 were weighed and added to 26.68 mL of deionized water and stirred thoroughly, and mixed uniformly at room temperature for 2 h to obtain a mixed solution A;

[0050] S1-2, 0.6 mL of acetic acid was added dropwise to the mixed solution A of step S1-1 at a speed of 10-15 drops / min, and mixed for 1 h to obtain a mixed solution B;

[0051] S1-3, the mixed solution B prepared in step S1-2 was mixed with 0.12 g of 2-amino terephthalic acid, mixed for 1 h, and then reacted at 110°C for 24 h. After the reaction was completed, the mixture was washed with water to remove excess reactants and surfactant F127, to obtain the NH2-MIL-88B(Fe);

[0052] S2, synthesis of NH2-MIL-88B(Fe)-MG132:

[0053] The NH2-MIL-88B(Fe) prepared in step S1 was vacuum dried to obtain NH2-MIL-88B(Fe) powder, and then 2 mg of the powder was weighed and mixed with 200 μL of proteasome inhibitor MG132 with a concentration of 5 mg / mL in 1800 μL of dimethyl sulfoxide, and stirred thoroughly for 24 h to obtain the NH2-MIL-88B(Fe)-MG132;

[0054] S3, synthesis of a cell membrane-coated nanodelivery platform:

[0055] S3-1, 5*10 6Raw264.7 macrophages, 10 μL of 100 mM / mL phenylmethylsulfonyl fluoride (PMSF) was added to 1 mL of RIPA lysis buffer, added to the macrophages, lysed on ice for 30 minutes, transferred to a 5 mL glass extruder and extruded at a constant speed for 30 times to break the cells under high pressure, and the cells were observed under a microscope to be broken 75%, to obtain a cell membrane solution;

[0056] S3-2, the NH2-MIL-88B(Fe)-MG132 prepared in step S2 was added to the cell membrane solution in step S3-1 and mixed by vortex, and then extruded 15 times by a liposome extruder to obtain the cell membrane-coated nano drug delivery platform NH2-MIL-88B(Fe)-MG132@M.

[0057] The synthesis process of the cell membrane-coated nano drug delivery platform in the embodiment is shown in the schematic diagram Figure 1 .

[0058] Figure 2 is a transmission electron microscope (TEM) image of NH2-MIL-88B(Fe).

[0059] Figure 3 is a transmission electron microscope (TEM) image of NH2-MIL-88B(Fe)-MG132@M) after phosphotungstic acid negative staining.

[0060] Figure 4 is a Zeta potential diagram of NH2-MIL-88B(Fe)-MG132 and NH2-MIL-88B(Fe)-MG132@M.

[0061] Figure 5 is an XPS diagram of NH2-MIL-88B(Fe).

[0062] The drug-loaded platform prepared in the embodiment of the application was subjected to the following experiments:

[0063] I. Identification of membrane proteins on NH2-MIL-88B(Fe)-MG132@M by SDS-PAGE electrophoresis and Coomassie blue, the operation method is as follows:

[0064] (1) Separation gel and concentrated gel pouring: pour the separation gel along the glass edge, and press the liquid surface with anhydrous ethanol. After it is solidified, remove the upper water. Pour the concentrated gel and insert the sample application comb;

[0065] (2) Protein loading: mix the protein sample and 6x protein loading buffer at a ratio of 5:1, heat at 100°C for 10 min to completely denature the protein. After cooling, add to the sample application hole, and use protein marker as a control;

[0066] (3) Electrophoresis: first 80V voltage, electrophoresis for about 30 min, so that the protein sample and marker enter the separation gel area; adjust the voltage to 120V, when the bands are completely separated and reach the lower end of the electrophoresis tank, stop electrophoresis;

[0067] (4) Staining and decolorization: after the operation is completed, carefully take out the gel and place it in the coomassie brilliant blue staining solution;

[0068] Then place it on a shaker for 1-2h of staining, and after the end, wash the gel with ultrapure water. Then decolorize with acetic acid decolorizing solution. Change the solution every 1h, and repeat the operation until the background is clean.

[0069] (5) Image processing: take a picture of the gel and mark it, and the results are as shown in Figure 6 .

[0070] From Figure 6 it can be seen that the NH2-MIL-88B(Fe)-MG132@M is coated with a cell membrane, the protein imprint of MIL-88@M is the same as that of the cell membrane, and MIL-88 does not have a corresponding protein imprint.

[0071] II. Drug release capacity experiment:

[0072] The specific method of drug release capacity is as follows: the drug release characteristics (MG132 release) of NH2-MIL-88B(Fe)-MG132 and NH2-MIL-88B(Fe)-MG132@M are determined by dialysis bag method, and the release medium is DMSO solution. A certain amount of NH2-MIL-88B(Fe)-MG132, NH2-MIL-88B(Fe)-MG132@M (containing NH2-MIL-88B 2mg) is transferred into a dialysis bag (relative molecular mass is 3000), the dialysis clamp is sealed, and then placed in a beaker containing 50ml PBS, and then placed in a constant temperature water bath shaker at (37±0.5)℃, 100r per min. Parallel operation for 3 times. At 0.1, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 60h time points, 1ml dialysate is taken, and the MG132 concentration is determined by ultraviolet determination. After each time the dialysate is taken, an equal amount of blank DMSO medium is supplemented. Calculate the cumulative release rate (Q), and draw the drug release curve.

[0073] The drug release capacity of NH2-MIL-88B(Fe)-MG132 and NH2-MIL-88B(Fe)-MG132@M drug delivery system is as shown in Figure 7 .

[0074] III. The phagocytosis of NH2-MIL-88B(Fe)-MG132 and NH2-MIL-88B(Fe)-MG132@M by CT26 cells at 0h, 2h, 4h and 8h was observed by laser confocal microscopy.

[0075] Phagocytosis assays were performed using CT26 cells, with FITC as the fluorescent dye, to examine the cell uptake behavior of the carrier. The procedure was as follows: CT26 cells were seeded in confocal glass dishes (cell density: 1x10⁶ cells / mL). 5 Cells (1 cell / well) were placed in a cell culture incubator and cultured overnight. The old culture medium was discarded, and medium containing free MIL-88-FITC and MIL-88@M-FITC was added to the corresponding wells. After culturing at different time points, the culture medium was discarded, and each well was washed three times with PBS. The nuclei were labeled with 4',6-diamidion-2-phenylindole (DAPI). Finally, the cells were observed and photographed using a laser confocal microscope. The phagocytic results of NH2-MIL-88B(Fe)-MG132 are shown below. Figure 8 The phagocytosis results of NH2-MIL-88B(Fe)-MG132@M are as follows: Figure 9 .

[0076] Figure 9 and Figure 8 The fluorescence intensity of the MIL-88@M group was stronger than that of the MIL-88 group, indicating that MIL-88@M has good cell entry ability.

[0077] IV. 100 μl of IR780-labeled NH2-MIL-88B(Fe)-MG132 and NH2-MIL-88B(Fe)-MG132@M were injected into tumor-bearing mice via the tail vein. The changes in fluorescence signal at the tumor site were monitored at different time points after injection using the VISQE small animal in vivo fluorescence imaging system. In vivo fluorescence images were observed from 0 to 108 hours, and fluorescence quantification was performed. The mouse in vivo imaging results of NH2-MIL-88B(Fe)-MG132 at different time points are shown below. Figure 10 The fluorescence quantitative results of in vivo imaging images of NH2-MIL-88B(Fe)-MG132 at different time points are as follows: Figure 11 In vivo imaging results of NH2-MIL-88B(Fe)-MG132@M in mice at different time points are as follows: Figure 12 Imaging results of various isolated tissues of mice 6 hours after administration of NH2-MIL-88B(Fe)-MG132@M are as follows: Figure 13 The fluorescence quantitative results of NH2-MIL-88B(Fe)-MG132@M in vivo imaging at different time points are as follows: Figure 14 .

[0078] Figure 12 Compared with Figure 10 MIL-88@M groups have the ability to target tumors under the mediation of macrophage membranes, and can accumulate in tumor sites faster and for a longer time. Figure 13 It can be seen that the drug can be well accumulated in tumor tissues.

[0079] Five, after administration, different composite nanomaterials, drugs or combined treatment groups of cells were detected, and the specific method was as follows:

[0080] First, each group of drugs 1) control group added pbs or no treatment; 2) NH2-MIL-88B(Fe) group, NH2-MIL-88B(Fe)-MG132 group, NH2-MIL-88B(Fe)-MG132@M all added 250 micrograms per milliliter of material; MG132 concentration is 10 μM. The cells used are CT26 cell lines. The results of Calcein / PI cell activity and cytotoxicity are as follows: Figure 15 ; The results of Annexin V-FITC cell apoptosis detection are as follows: Figure 16 From the cell activity and toxicity test and flow cytometry apoptosis test, it can be concluded that NH2-MIL-88B(Fe)-MG132@M has the most significant killing effect on tumor cells, has higher cytotoxicity, and can effectively kill tumor cells.

[0081] After 14 days of injection, the tumors of different groups of mice were detected, and the tumor volume changes were as follows: Figure 17 ; The tumor weight is as follows: Figure 18 From the figure, it can be seen that NH2-MIL-88B(Fe)-MG132@M, which is obtained by chemical kinetics combined with epigenetic regulation, has the best tumor treatment effect, and the tumor has obvious regression after treatment compared with the control group.

[0082] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled persons in the art, without departing from the principles of the present application, several improvements and refinements can be made, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A method for preparing a cell membrane-coated nanodelivery platform, characterized in that, The method comprises the following steps: S1, synthesis of NH2-MIL-88B(Fe): S1-1, FeCl3·6H2O and F127 are added into deionized water and fully stirred, and the mixture is fully mixed at room temperature for 2h to obtain a mixed solution A; S1-2, acetic acid is added into the mixed solution A of step S1-1 at a speed of 10-15 drops / min, and the mixture is mixed for 1-1.5h to obtain a mixed solution B; S1-3, the mixed solution B prepared in step S1-2 is mixed with 2-amino terephthalic acid, and then the reaction is carried out, after the reaction is completed, the mixture is washed with water to remove excess reactants and surfactant F127, thereby obtaining the NH2-MIL-88B(Fe); S2, synthesis of NH2-MIL-88B(Fe)-MG132: The NH2-MIL-88B(Fe) prepared in step S1 is vacuum dried to obtain NH2-MIL-88B(Fe) powder, which is then mixed with proteasome inhibitor MG132 in dimethyl sulfoxide, and fully stirred at room temperature for 24h to obtain the NH2-MIL-88B(Fe)-MG132; S3, synthesis of a cell membrane-coated nano drug delivery platform: S3-1, benzylsulfonyl fluoride is added into RIPA lysis buffer to obtain a mixed solution, the mixed solution is added into cells, and the cells are lysed on ice for 30min, and the cells are extruded at a constant speed for 30-50 times by using a glass extruder to break the cells under high pressure until the cells are broken by 70%-90% under microscopic observation, thereby obtaining a cell membrane solution; S3-2, the NH2-MIL-88B(Fe)-MG132 prepared in step S2 is added into the cell membrane solution in step S3-1 and vortexed, and then extruded 15 times by using a liposome extruder, thereby obtaining the cell membrane-coated nano drug delivery platform NH2-MIL-88B(Fe)-MG132@M; In step S2, the mass-volume ratio of the NH2-MIL-88B(Fe) powder, the proteasome inhibitor MG132 and dimethyl sulfoxide is 2-5mg:200μL:1800μL, and the concentration of the proteasome inhibitor MG132 is 5mg / mL.

2. The method of claim 1, wherein the cell membrane-coated nanodelivery platform is prepared by the steps of: In step S1-1, the mass ratio of FeCl3·6H2O and F127 is 0.75-1.

00.

3. The method for preparing the cell membrane-coated nanodrug delivery platform according to claim 1, characterized in that, In step S1-1, the concentration of FeCl3·6H2O is 0.013-0.015g / mL.

4. The method for preparing the cell membrane-coated nanodrug delivery platform according to claim 1, characterized in that, In step S1-2, the volume ratio of acetic acid to the mixed solution A is 0.4-0.7:23-30.

5. The method for preparing the cell membrane-coated nanodrug delivery platform according to claim 1, characterized in that, In step S1-3, the mass ratio of 2-amino terephthalic acid to FeCl3·6H2O added is 1-1.5:

3.

6. The method for preparing the cell membrane-coated nanodrug delivery platform according to claim 1, characterized in that, In step S1-3, the temperature of the reaction is 100-120℃, and the time is 20-24h.

7. The method for preparing the cell membrane-coated nanodrug delivery platform according to claim 1, characterized in that, The concentration of benzylsulfonyl fluoride in the mixed solution in step S3-1 is 0.9-1 mmol / mL; the ratio of the volume of the mixed solution to the number of cells is 0.9-1.1 ml: 5*10 6 cells.

8. The method for preparing the cell membrane-coated nanodrug delivery platform according to claim 1, characterized in that, In step S3-1, the cells are macrophages or tumor cells.

9. The method for preparing the cell membrane-coated nanodrug delivery platform according to claim 1, characterized in that, The ratio of NH2-MIL-88B(Fe)-MG132 to cell solution in step S3-2 is added according to 0.5-5 mg NH2-MIL-88B(Fe)-MG132 per 5*10 6 cells. The ratio of NH2-MIL-88B(Fe)-MG132 to cell solution in step S3-2 is added according to 0.5-5 mg NH2-MIL-88B(Fe)-MG132 per 5*10 6 cells.

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