CN114409914B - Preparation method of iron-based metal organic framework composite material with MOF-On-MOF framework, obtained product and application - Google Patents
Preparation method of iron-based metal organic framework composite material with MOF-On-MOF framework, obtained product and application Download PDFInfo
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Abstract
The invention discloses a preparation method of an iron-based metal organic framework composite material with an MOF-On-MOF framework, an obtained product and application. The composite material synthesized by the invention has uniform size, and the second MOF layer not only improves the drug loading, but also can be used as a gating entity to avoid premature drug leakage. The composite material has good pH and GSH response capability, has catalytic activity of peroxidase-like enzyme under acidic condition, and can catalyze H 2 O 2 OH is generated, shows the potential of the chemodynamic therapy for treating the cancer, well expands the requirement of the practical application field for treating the cancer by using the chemo-therapy and the chemodynamic therapy in a combined way, and provides possibility for clinical application.
Description
Technical Field
The invention relates to a preparation method of an iron-based metal organic framework composite material with an MOF-On-MOF framework, and relates to a preparation method of an iron-based metal organic framework composite material with peroxidase-like activity and good pH/GSH response in an acidic condition, a product obtained by the method, and application of the product as a drug carrier in combined treatment of cancer tissues in chemotherapy and chemical dynamic therapy.
Background
Traditional chemotherapy remains one of the important methods for tumor treatment. However, poor cellular uptake of a single drug, short half-life of the drug, and non-specific distribution in the organism severely limit its therapeutic efficacy. In order to overcome these obstacles, drug delivery carriers such as polymers, molecular vesicles, mesoporous silicon, and the like have attracted much attention because they can stabilize drug molecules and achieve targeted delivery of drug molecules to pathological tissues. Although the research on these drug carriers has been advanced, there are still some problems in that 1) a low drug loading requires a large dose to achieve a certain therapeutic effect, thereby imposing a burden on normal tissues and organs; 2) The controlled release effect is not ideal, so that unnecessary medicaments leak in advance, and serious side effects are caused; 3) Too complex drug delivery systems introduce more foreign substances, which pose a serious threat to biosafety. An ideal drug delivery system generally has the characteristics of large drug loading, excellent controlled release performance, simple system, good biocompatibility and the like.
Metal-Organic Framework (MOFs) are one-, two-or three-dimensional periodic porous materials formed by self-assembly of Organic ligands and Metal ions or ion clusters. As a novel organic-inorganic hybrid crystalline porous material, a metal organic framework material draws wide attention of various social circles by virtue of irreplaceable advantages of the metal organic framework material. Compared with the drug carrier, the metal organic framework material has a series of advantages of ultrahigh specific surface area and pore volume, adjustable pore size, easy functionalization, catalytic activity and the like. These significant advantages have led to the development of metal organic framework materials with great potential for use in cancer therapy.
To date, many reports have been made on metal-organic framework materials as drug carriers. Currently, metal organic framework materials are loaded with drugs mainly by two ways. One is directly loaded into the hole of the material, the other is to form a binding site on the surface of the material by a post-modification technology, and after the drug is loaded, a cover is combined with the binding site to block the hole, so that the drug is prevented from leaking in non-pathological tissues. The former preparation conditions are relatively simple, but the controlled release of the drug in the diseased tissue is difficult to realize. This disadvantage can be avoided well by the latter, which however also suffers from the disadvantages of cumbersome preparation and low loading.
Disclosure of Invention
Aiming at the defects of the existing drug carrier, the invention provides a preparation method of an iron-based metal organic framework composite material with an MOF-On-MOF framework and an obtained product, the preparation method is simple in preparation process and easy to operate, the obtained iron-based metal organic framework composite material can be used as a drug carrier, not only has higher drug loading capacity, but also has good peroxidase-like activity and pH sensitivity under an acidic condition, has response release capacity, can control drug release, meets the requirements of the practical application field On the drug carrier in various aspects to a great extent, and greatly promotes the application progress of the metal organic framework material in the field of cancer tissue treatment.
The invention adopts the following technical scheme:
a preparation method of an iron-based metal organic framework composite material with an MOF-On-MOF framework comprises the following steps: reacting NH 2 Dispersing MIL-88B into absolute ethyl alcohol, then adding organic ligand 2-amino terephthalic acid and ferric trichloride hexahydrate, and obtaining the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework through a solvothermal method, which can also be called as an MOF-On-MOF nanocrystal material.
Further, said NH 2 MIL-88B is a Metal Organic Framework (MOF) material, NH 2 -MIL-88B may be prepared by methods disclosed in the prior art.
In one embodiment of the present invention, NH 2 -MIL-88B is prepared by a solvothermal method comprising: dissolving ferric trichloride hexahydrate and organic ligand 2-amino terephthalic acid in absolute ethyl alcohol by ultrasonic waves, stirring and reacting for 1-2 hours at 35-45 ℃, collecting products after reaction, and washing to obtain NH 2 -MIL-88B. Wherein the molar ratio of ferric trichloride hexahydrate to 2-amino terephthalic acid is 1:1, and the concentration of ferric trichloride hexahydrate in absolute ethyl alcohol is 9-11mM (mmol/L).
Further, NH when synthesizing the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework 2 -MIL-88B, 2-aminoterephthalic acid and ferric chloride hexahydrate in a mass ratio of 4-8.
Further, NH is generated when the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework is synthesized 2 The concentration of-MIL-88B in absolute ethanol is 0.2-0.4 mg/mL.
Furthermore, when the nanometer iron-based metal organic framework composite material with the MOF-On-MOF framework is synthesized, the reaction temperature of a solvothermal method is 35-45 ℃, and the reaction time is 1-2 hours.
The iron-based metal organic framework composite material with the MOF-On-MOF framework obtained by the method can be used as a drug carrier and used for combined treatment of chemotherapy and chemodynamic treatment of cancer tissues. The drug may be a variety of chemotherapeutic drugs, such as doxorubicin hydrochloride (DOX).
Further, the invention also provides a preparation method of the iron-based metal organic framework composite material with the medicine-carrying MOF-On-MOF framework, which comprises the following steps: reacting NH 2 -MIL-88B is dispersed in absolute ethyl alcohol containing drugs, then organic ligand 2-amino terephthalic acid and ferric trichloride hexahydrate are added, and a drug-loaded iron-based metal organic framework composite material with an MOF-On-MOF framework is obtained through a solvothermal method, and the composite material can realize drug controlled release with pH/GSH dual response.
Further, said NH 2 The MIL-88B can be prepared according to the method, the drug is added in the preparation process of the iron-based metal organic framework composite material, the drug loading is realized, the process flow is simplified, the drug loading capacity can be improved, the reaction condition in the synthesis process is mild, and the adverse effect on the drug performance can not be generated.
Further, the drug may be various chemotherapeutic drugs, such as doxorubicin hydrochloride and the like.
Further, NH 2 -MIL-88B, 2-aminoterephthalic acid and ferric chloride hexahydrate in a mass ratio of 4-8.
Further, NH 2 -the mass ratio of MIL-88B to the medicament is 2-4:5.
further, the concentration of ferric chloride hexahydrate is 1-1.5 mg/mL.
Furthermore, the reaction temperature of the solvothermal method is 35-45 ℃, and the reaction time is 1-2 hours.
In a specific embodiment of the invention, the invention provides a preparation method of an iron-based metal organic framework composite material (DOX @ MIL-On-MIL) of an MOF-On-MOF framework loaded with doxorubicin hydrochloride (DOX), which comprises the following steps:
(1) Ultrasonically dissolving ferric trichloride hexahydrate and organic ligand 2-amino terephthalic acid in absolute ethyl alcohol by a solvothermal method, uniformly stirring and reacting for 1.5 hours at 40 ℃, centrifuging the obtained product, repeatedly washing the product with absolute ethyl alcohol for 3~5 times, and drying to obtain NH 2 -MIL-88B。
（2）Subjecting the NH prepared in step (1) to a MOF-On-MOF strategy based On a solvothermal method 2 Ultrasonically dispersing MIL-88B in absolute ethyl alcohol containing doxorubicin hydrochloride again, then sequentially adding an organic ligand 2-aminoterephthalic acid and ferric trichloride hexahydrate, ultrasonically dissolving in a mixed solution, and uniformly stirring and reacting for 1.5 hours at 40 ℃ to obtain an iron-based metal organic framework material DOX @ MIL-On-MIL with an MOF-On-MOF framework.
The invention is based On a solvothermal method, and adopts an MOF-On-MOF strategy to synthesize a brand new iron-based nano composite material, namely an iron-based metal organic framework composite material (named as MIL-On-MIL) with an MOF-On-MOF framework. Chemotherapeutic drugs such as doxorubicin hydrochloride (DOX) and the like are loaded in the holes of the iron-based metal organic framework composite material with the MOF-On-MOF framework, and the drug loading system can achieve the effect of controlling drug release by pH/GSH. The aperture of the synthesized nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework is well matched with the size of medicines such as doxorubicin hydrochloride (DOX), so that higher loading capacity can be achieved. NH compared to a monolayer 2 The synthesized nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework has a second MOF layer as a gating entity, so that the nano-scale iron-based metal organic framework composite material has higher drug loading capacity and enhanced drug release control capacity, and the drug loading system has a pH/GSH (glutathione) controlled release phenomenon in the drug release process. In addition, experiments prove that the material has good peroxidase-like activity and pH sensitivity under an acidic condition, meets various requirements of the practical application field on drug carriers to a considerable extent, and greatly promotes the application progress of the metal organic framework material in the field of cancer tissue treatment.
The invention has the following specific beneficial effects:
(1) The invention designs and synthesizes the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework by adopting an MOF-On-MOF strategy with simple process, and the nano-scale iron-based metal organic framework composite material is a porous material formed by self-assembly On the basis of a single-layer MOF. The second MOF layer greatly enhances the porosity of the material, not only improves the drug loading, but also can be used as a gating entity, and avoids the early leakage of drug molecules.
(2) The nanometer iron-based metal organic framework composite material with the MOF-On-MOF framework is characterized in that ligand molecules are bridged On the surface of a first layer of main MOF and adsorb free metal ions in a solvent, so that a second layer of object MOF forms crystal boundary nucleation On the surface of the main MOF and continues to grow, the acting force between double layers of MOF is enhanced, and the MOF-On-MOF framework is finally obtained, so that the material has high drug loading capacity, and the drug loading capacity is verified to be 14.4wt% and is nearly 2 times of that of a single layer of MOF.
(3) The size of the metal organic framework used as a drug carrier reported in the prior art is mostly in the micron level, and the clinical application in the biological field is greatly limited, the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework has the size of about 200 nm and uniform size, can be targeted to a focus part by enhancing the permeation and retention (EPR) effect and is taken by tumor cells, so that the drug release system is hopeful to realize injection therapy, and the application of the material in the biological field is promoted.
(4) The invention encapsulates chemotherapeutic drug doxorubicin hydrochloride and the like to NH by an MOF-On-MOF strategy 2 In MIL-88B, the synthesized nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework has catalytic activity similar to peroxidase in the slightly acidic environment of cancer tissues, can catalyze hydrogen peroxide to generate OH, and shows the potential of treating cancers by chemodynamic therapy (CDT). The nanometer iron-based metal organic framework composite material with the MOF-On-MOF framework loaded with the adriamycin hydrochloride and other medicines can realize the combined treatment of chemotherapy and chemical dynamic therapy and enhance the treatment effect of cancer tissue parts.
(5) The nano-scale iron-based metal organic framework material with the MOF-On-MOF framework synthesized by the invention has good peroxidase-like activity and pH sensitivity under an acidic condition, has excellent pH and GSH response capability, can control the release of the drug, meets the requirements of the practical application field On various aspects of drug carriers to a certain extent, well expands the requirements of the practical application field On the combined treatment of cancer by chemotherapy and chemical dynamic therapy, and provides potential possibility for clinical application of the nano-scale iron-based metal organic framework material.
Drawings
FIG. 1 is an X-ray diffraction (XRD) pattern of a metal organic framework material before and after loading with a drug.
FIG. 2 is a Scanning Electron Microscope (SEM) and a Transmission Electron Microscope (TEM) image of the metal organic framework material before and after loading with the drug.
FIG. 3 is a graph showing the drug loading and drug release curves of the metal organic framework composite material, wherein a is the ultraviolet absorption spectrum of DOX after hydrochloric acid digestion, neutralization and volume determination of each sample in the legend, and b is DOX @ NH 2 DOX release profiles of MIL-88B in different pH buffers, c is the DOX release profile of DOX @ MIL-On-MIL in different pH buffers, d is the DOX release profile of DOX @ MIL-On-MIL in different GSH concentrations.
FIG. 4 is a diagram showing Peroxidase (POD) -like activity of a metal-organic framework composite material, in which a represents a TMB solution and NH 2 H of MIL-88B at various concentrations 2 O 2 Ultraviolet-visible spectrum after 10 min incubation, b is H of TMB solution and DOX @ MIL-On-MIL at different concentrations 2 O 2 Uv-vis spectrum after 10 min incubation.
FIG. 5 is the pH-responsive peroxidase-like activity of a metal-organic framework composite DOX @ MIL-On-MIL.
FIG. 6 shows the cell viability of the metal-organic framework composite incubated with cells for 24 hours.
Figure 7 is a flow cytometry uptake assay of metal organic framework composites incubated with cells.
FIG. 8 is a fluorescent image of the co-incubation of the metal organic framework composite with cells for various periods of time.
Detailed Description
The contents of the present invention will be further described with reference to the following examples, which are not intended to limit the scope of the present invention, and various modifications and variations can be made by those skilled in the art without inventive changes based on the technical solutions of the present invention.
Example 1
(1) By using a solvent thermal methodThe method is that 18 mg organic ligand 2-amino terephthalic acid is added into 10 mL absolute ethyl alcohol, 27 mg ferric chloride hexahydrate is added after complete ultrasonic dissolution. Stirring and reacting for 1.5 hours at the uniform speed under the condition of 40 ℃, collecting and centrifuging, washing 3~5 times by absolute ethyl alcohol to obtain 3 mg metal organic framework material NH 2 -MIL-88B。
(2) NH prepared as above 2 And (3) completely ultrasonically dispersing MIL-88B into 10 mL absolute ethyl alcohol, then sequentially adding 9 mg organic ligand 2-aminoterephthalic acid and 13.5 mg ferric chloride hexahydrate, ultrasonically dissolving into a mixed solution, and uniformly stirring and reacting for 1.5 hours at 40 ℃ to obtain 5.5 mg of MOF-On-MOF iron-based metal organic framework composite material, namely MIL-On-MIL.
Example 2
(1) By adopting a solvothermal method, 18 mg organic ligand 2-amino terephthalic acid is added into 10 mL absolute ethyl alcohol, and 27 mg ferric chloride hexahydrate is added after complete ultrasonic dissolution. Stirring and reacting for 1.5 hours at the uniform speed at the temperature of 40 ℃, collecting and centrifuging, washing 3~5 times by absolute ethyl alcohol to obtain 3 mg metal organic framework material NH 2 -MIL-88B。
(2) NH prepared as above 2 -MIL-88B is completely ultrasonically dispersed in absolute ethyl alcohol (10 mL) containing doxorubicin hydrochloride (5 mg), then 9 mg organic ligand 2-aminoterephthalic acid and 13.5 mg ferric chloride hexahydrate are sequentially added and ultrasonically dissolved in the mixed solution, and the mixture is uniformly stirred and reacts for 1.5 hours at 40 ℃ to obtain 6.4 mg of iron-based metal organic framework material DOX @ MIL-On-MIL, namely DMM, with an MOF-On-MOF framework.
Comparative example 1
Ultrasonically dissolving 18 mg organic ligand 2-amino terephthalic acid and 27 mg ferric trichloride hexahydrate in absolute ethyl alcohol (10 mL) containing doxorubicin hydrochloride (5 mg) by adopting a one-pot solvothermal method, carrying out uniform-speed stirring reaction for 1.5 hours at the temperature of 40 ℃, centrifuging the obtained product, repeatedly washing 3~5 times by using the absolute ethyl alcohol, and drying to obtain an iron-based metal organic framework material DOX @ NH 2 -MIL-88B。
Verification example
FIG. 1 is a schematic view of an embodimentAnd NH obtained in comparative example 2 -MIL-88B、MIL-On-MIL（NH 2 -MIL-88B@ NH 2 -MIL-88B）、DOX@MIL-On-MIL、DOX@NH 2 XRD pattern of MIL-88B, it can be seen that DOX @ MIL-On-MIL still maintains the intact crystal structure after loading with drug.
FIG. 2 shows the example obtained and the NH obtained in comparative example 2 The scanning electron microscope and transmission electron microscope images of-MIL-88B, MIL-On-MIL and DOX @ MIL-On-MIL (DMM) show that the shape of MIL-On-MIL is not changed before and after loading the medicine, and the obtained DOX @ MIL-On-MIL has a core-shell structure and the size of the DOX @ MIL-On-MIL is about 200 nanometers.
The drug loading, pH response, GSH response, peroxidase-like activity, etc. of the products prepared in the above examples and comparative examples were tested as follows:
1. 1 mg DOX @ MIL-On-MIL (DMM) of example 2 and DOX @ NH of comparative example 1 were taken, respectively 2 MIL-88B (DM), digesting and destroying the metal organic framework by 10 mu L of hydrochloric acid, neutralizing to 5 mL, scanning in a full waveband by using an ultraviolet spectrophotometer, amplifying a characteristic absorption area of the adriamycin at the wavelength of 480 nm, and then calculating the drug loading according to a standard curve of the adriamycin hydrochloride. The drug loading calculation formula is as follows:
wherein (wt%) is the drug loading, M is the mass of doxorubicin hydrochloride loaded in the metal organic framework, and M is the total mass of the products prepared in examples and comparative examples.
The drug loading results are shown in FIG. 3a, from which it can be seen that the drug loading of DOX @ MIL-On-MIL is 14.4wt%, while that of DOX @ NH 2 The drug loading rate of-MIL-88B is 7.4wt%, and the drug loading rate is obviously improved.
2. DOX @ MIL-On-MIL of example 2, DOX @ NH of comparative example 1 2 MIL-88B was subjected to light-shielded drug release experiments in PBS at pH 7.4, 6.5 and 5.0, respectively. Specifically, samples of 3 mg of the examples and comparative examples, respectively, were taken for sustained release experiments in 10 mL PBS.A certain volume of supernatant was aspirated at different intervals (0 h,0.5 h,1 h,2 h,4 h,6 h,8 h,10 h,12 h,14 h,16 h,18 h), the possible presence of a trace amount of precipitate was removed by centrifugation, the withdrawn volume was then supplemented with PBS at a pH corresponding to the pH, and the possible precipitate was transferred back to the sustained-release solution. The absorbance was measured at a wavelength of 480 nm and the drug release was calculated from the standard curve for doxorubicin hydrochloride.
The drug release profiles at different pH are shown in FIGS. 3b and 3c, from which it can be seen that the drug release is greater under acidic conditions of pH 5.0 and pH 6.5 and less under neutral conditions.
3. The DOX @ MIL-On-MIL of example 2 was subjected to a drug release test in GSH (glutathione) solutions at concentrations of 0.01 mM,0.1 mM,5 mM,10 mM, respectively, and the drug release amount was calculated from the standard curve of doxorubicin hydrochloride in the same manner as in the above-mentioned method 2.
The drug release profile at different GSH (glutathione) concentrations is shown in fig. 3d, where it can be seen that more drug is released in the 10 mM GSH solution and less drug is released in the 0.01 mM GSH solution.
4. DOX @ MIL-On-MIL and NH of example 2 2 Separately adding-MIL-88B to solutions containing different concentrations of H 2 O 2 In PBS solution (pH = 4.0), DOX @ MIL-On-MIL and NH were compared using 3,3,5,5-Tetramethylbenzidine (TMB) 2 Peroxidase-like (POD) activity of MIL-88B, and the final concentrations of sample and TMB in the reaction system were 250. Mu.g/mL and 1.0 mM, respectively. After 10 min of incubation, the peroxidase-like activity was verified from the intensity of the signal peak in the oxidation state of TMB (oxTMB) at 652 nm.
The result of the peroxidase-like activity test is shown in FIG. 4, from which it can be seen that DOX @ MIL-On-MIL still retains NH 2 Peroxidase-like activity inherent to MIL-88B.
5. DOX @ MIL-On-MIL from example 2 was added to a solution containing 1mM H 2 O 2 The peroxidase-like enzyme (POD) activity of DOX @ MIL-On-MIL was tested in different pH buffers using 3,3,5,5-Tetramethylbenzidine (TMB) in PBS solutions of different pH (7.4, 6.5, 5.0, 4.0) concentrations,the final concentrations of sample and TMB in the reaction were 250. Mu.g/mL and 1.0 mM, respectively. Peroxidase-like activities at different pH values are shown in FIG. 5, and it can be seen from the figure that DOX @ MIL-On-MIL after drug loading still has pH-responsive peroxidase-like activities under acidic conditions, and can be used for the chemokinetic treatment of cancer tissues.
6. Reacting NH 2 -MIL-88B，DOX@NH 2 MIL-88B, DOX @ MIL-On-MIL and 4T1 cells were incubated together, and cell viability was calculated by the CCK-8 method. The results are shown in FIG. 6, NH at a maximum concentration of 100 ppm 2 After the MIL-88B and the cells are incubated together for 24 hours, the cells still maintain higher cell viability, which indicates that the iron-based metal organic framework material has good biocompatibility in a concentration of 100 ppm. After drug loading, DOX @ NH 2 MIL-88B and DOX @ MIL-On-MIL exhibited significant dose-dependent inhibition of cells, and DOX @ MIL-On-MIL was more potent in killing 4T1 cells due to interaction with DOX @ NH 2 MIL-88B has a higher DOX drug load than DOX @ MIL-On-MIL. Flow cytometry uptake analysis and fluorescence inverted microscopy were performed on the co-incubated cells and the results are shown in figures 7 and 8. The result proves that the uptake behavior of the cell to the material meets the requirements of the clinical application field on various aspects of the metal organic framework to the great extent, and is beneficial to promoting the application progress of the metal organic framework material in the aspect of cancer treatment.
From the experimental results, the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework has excellent pH and GSH response capability, has catalytic activity similar to peroxidase in the slightly acidic environment of cancer tissues, shows the potential of the chemodynamic therapy (CDT) for treating cancers, can realize the combined treatment of chemotherapy and chemodynamic therapy, enhances the treatment effect of cancer tissue parts, and can be used for local chemotherapy of cancer tissues.
Claims (14)
1. A preparation method of an iron-based metal organic framework composite material with an MOF-On-MOF framework is characterized by comprising the following steps: reacting NH 2 dispersing-MIL-88B into anhydrous ethanol, and adding into organic machine2-amino terephthalic acid and ferric trichloride hexahydrate are subjected to a solvothermal method to obtain the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework.
2. The method for preparing a polycarbonate resin composition according to claim 1, wherein: NH 2 -MIL-88B, 2-aminoterephthalic acid and ferric chloride hexahydrate in a mass ratio of 4-8.
3. The method according to claim 1 or 2, characterized in that: NH 2 -MIL-88B at a concentration of 0.2-0.4 mg/mL in anhydrous ethanol.
4. The method of claim 1, wherein: the reaction temperature of the solvothermal method is 35-45 ℃, and the reaction time is 1-2 hours.
5. The method of claim 1, wherein: the NH 2 -MIL-88B is prepared by a solvothermal method, ferric trichloride hexahydrate and organic ligand 2-amino terephthalic acid are ultrasonically dissolved in absolute ethyl alcohol, the mixture is stirred and reacts for 1 to 2 hours at the temperature of between 35 and 45 ℃, and products are collected and washed after the reaction to obtain NH 2 -MIL-88B。
6. The method according to claim 5, wherein: preparation of NH 2 When MIL-88B is adopted, the molar ratio of ferric trichloride hexahydrate to 2-amino terephthalic acid is 1:1, and the concentration of ferric trichloride hexahydrate in absolute ethyl alcohol is 9-11 mmol/L.
7. The method for preparing the iron-based metal-organic framework composite material with the MOF-On-MOF framework, which is prepared by the method for preparing the iron-based metal-organic framework composite material with the MOF-On-MOF framework, of any one of claims 1 to 6.
8. Use of an iron-based metal-organic framework composite material of the MOF-On-MOF framework of claim 7 for the preparation of a drug carrier.
9. Use according to claim 8, characterized in that: the medicine is doxorubicin hydrochloride.
10. A preparation method of an iron-based metal organic framework composite material with a medicine-carrying MOF-On-MOF framework is characterized by comprising the following steps: reacting NH 2 Dispersing MIL-88B in absolute ethyl alcohol containing a drug, then adding an organic ligand 2-aminoterephthalic acid and ferric trichloride hexahydrate, and obtaining the iron-based metal organic framework composite material with the MOF-On-MOF framework of the drug loading through a solvothermal method.
11. The method of claim 10, wherein: the medicine is doxorubicin hydrochloride.
12. The method of claim 10, wherein: NH (NH) 2 -mass ratio of MIL-88B, 2-aminoterephthalic acid and ferric trichloride hexahydrate is 4-8, concentration of ferric trichloride hexahydrate is 1-1.5 mg/mL.
13. The method of claim 10, wherein: NH (NH) 2 The mass ratio of MIL-88B to the medicine is 2-4:5.
14. the method of claim 10, wherein: the reaction temperature of the solvothermal method is 35-45 ℃, and the reaction time is 1-2 hours.
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