CN114409914A - 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 PDF

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CN114409914A
CN114409914A CN202210031552.3A CN202210031552A CN114409914A CN 114409914 A CN114409914 A CN 114409914A CN 202210031552 A CN202210031552 A CN 202210031552A CN 114409914 A CN114409914 A CN 114409914A
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谢曼修
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Sun Yat Sen University Cancer Center
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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 catalyzeChanging to H2O2OH 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

Preparation method of iron-based metal organic framework composite material with MOF-On-MOF framework, obtained product and application
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 NH2Dispersing 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 NH2MIL-88B is a Metal Organic Framework (MOF) material, NH2-MIL-88B may be prepared by methods disclosed in the prior art.
In one embodiment of the present invention, NH2-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 NH2-MIL-88B. Wherein, ferric trichloride hexahydrate and 2-amino-p-phenylene-bisThe molar ratio of formic acid is 1:1, and the concentration of ferric trichloride hexahydrate in absolute ethyl alcohol is 9-11mM (mmol/L).
Further, NH is generated when the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework is synthesized2The mass ratio of the-MIL-88B, the 2-amino terephthalic acid and the ferric trichloride hexahydrate is 4-8:18: 27.
Further, NH is generated when the nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework is synthesized2The 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 NH2the-MIL-88B is dispersed in absolute ethyl alcohol containing drugs, then organic ligand 2-amino terephthalic acid and ferric trichloride hexahydrate are added, and the iron-based metal organic framework composite material with the MOF-On-MOF framework and carrying drugs is obtained through a solvothermal method, and the composite material can realize drug controlled release with pH/GSH dual response.
Further, said NH2The 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, NH2-MIL-88B, 2-aminoThe mass ratio of the terephthalic acid to the ferric trichloride hexahydrate is 4-8:18: 27.
Further, NH2The mass ratio of MIL-88B to the medicine 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 preparation method of the iron-based metal organic framework composite material (DOX @ MIL-On-MIL) of the MOF-On-MOF framework loaded with doxorubicin hydrochloride (DOX) 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 with absolute ethyl alcohol for 3-5 times, and drying to obtain NH2-MIL-88B。
(2) Subjecting the NH prepared in step (1) to a MOF-On-MOF strategy based On a solvothermal method2Ultrasonically dispersing MIL-88B in absolute ethyl alcohol containing doxorubicin hydrochloride again, then sequentially adding an organic ligand 2-amino terephthalic acid and ferric chloride hexahydrate, ultrasonically dissolving in a mixed solution, and uniformly stirring and reacting for 1.5 hours at 40 ℃ to obtain the iron-based metal organic framework material DOX @ MIL-On-MIL with the 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 single layer2-MIL-88B iron-based metal organic framework material,the synthesized nano-scale iron-based metal organic framework composite material with the MOF-On-MOF framework has higher drug loading capacity and enhanced drug release control capacity due to the fact that the second MOF layer is used as a gating entity, and the drug loading system has a pH/GSH 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 14.4wt% and is nearly 2 times of that of a single layer of MOF through verification.
(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 up by tumor cells, so that the drug release system hopefully realizes injection treatment, and the application of the material in the biological field is promoted.
(4) The invention relates to the preparation of MOF-On-MOFStrategy for encapsulating chemotherapeutic drugs such as doxorubicin hydrochloride to NH2In 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 fixing of each sample in the legend, and b is DOX @ NH2-DOX release profile of MIL-88B in different pH buffers, c is DOX @ MIL-On-MIL in different pH buffers, d is DOX release profile of DOX @ MIL-On-MIL in different GSH concentrations.
FIG. 4 is a diagram showing peroxidase-like (POD) activity of a metal-organic framework composite material, wherein a is TMB solution and NH2H of MIL-88B at various concentrations2O2Ultraviolet-visible spectrum after 10 min incubation, b is H of TMB solution and DOX @ MIL-On-MIL at different concentrations2O2UV-Ke after 10 min incubationSee the spectrum.
FIG. 5 is the pH-responsive peroxidase-like activity of the 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 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 adopting a solvothermal method, 18 mg of organic ligand 2-amino terephthalic acid is added into 10 mL of absolute ethyl alcohol, and 27 mg of ferric trichloride hexahydrate is added after complete ultrasonic dissolution. Stirring and reacting at a uniform speed for 1.5 hours at 40 ℃, collecting and centrifuging, and washing for 3-5 times by using absolute ethyl alcohol to obtain 3 mg of metal organic framework material NH2-MIL-88B。
(2) NH prepared as above2And (3) completely ultrasonically dispersing MIL-88B into 10 mL of absolute ethyl alcohol, then sequentially adding 9 mg of organic ligand 2-amino terephthalic acid and 13.5 mg of ferric chloride hexahydrate, ultrasonically dissolving into the 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 of organic ligand 2-amino terephthalic acid is added into 10 mL of absolute ethyl alcohol, and 27 mg of ferric trichloride hexahydrate is added after complete ultrasonic dissolution. Stirring and reacting at a uniform speed for 1.5 hours at 40 ℃, collecting and centrifuging, and washing for 3-5 times by using absolute ethyl alcohol to obtain 3 mg of metal organic framework material NH2-MIL-88B。
(2) NH prepared as above2And (3) completely ultrasonically dispersing MIL-88B into absolute ethyl alcohol (10 mL) containing doxorubicin hydrochloride (5 mg), then sequentially adding 9 mg of organic ligand 2-amino terephthalic acid and 13.5 mg of ferric chloride hexahydrate, ultrasonically dissolving into a mixed solution, and uniformly stirring at a constant speed for reacting for 1.5 hours at 40 ℃ to obtain 6.4 mg of an iron-based metal organic framework material DOX @ MIL-On-MIL with an MOF-On-MOF framework, namely DMM.
Comparative example 1
Ultrasonically dissolving 18 mg of organic ligand 2-amino terephthalic acid and 27 mg of ferric chloride hexahydrate in absolute ethyl alcohol (10 mL) containing doxorubicin hydrochloride (5 mg) by adopting a one-pot solvothermal method, wherein the mixture is stirred at a uniform speed at 40 ℃ for reaction for 1.5 hours, centrifuging the obtained product, repeatedly washing the product for 3-5 times by using the absolute ethyl alcohol, and drying the product to obtain the iron-based metal organic framework material DOX @ NH2-MIL-88B。
Verification example
FIG. 1 shows NH obtained in examples and comparative examples2-MIL-88B、MIL-On-MIL（NH2-MIL-88B@ NH2-MIL-88B）、DOX@MIL-On-MIL、DOX@NH2XRD 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 obtained example and the comparative NH2Scanning electron microscope and transmission electron microscope images of MIL-88B, MIL-On-MIL and DOX @ MIL-On-MIL (DMM), as can be seen from the images, the shape of the MIL-On-MIL is not changed before and after loading the drug, 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 taken2MIL-88B (DM), digesting and destroying the metal organic framework by 10 mu L of hydrochloric acid, neutralizing to a constant volume of 5 mL, and amplifying the characteristic absorption area of the adriamycin at the position of 480 nm of wavelength by using a full-wave-band scanning of an ultraviolet spectrophotometerThe drug loading was then calculated according to a standard curve for doxorubicin hydrochloride. The drug loading calculation formula is as follows:
Figure 517952DEST_PATH_IMAGE001
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.
Drug loading results are shown in FIG. 3a, where it can be seen that the drug loading of DOX @ MIL-On-MIL is 14.4wt%, while that of DOX @ NH2The drug loading rate of-MIL-88B is 7.4wt%, and the drug loading rate is obviously improved.
2. The DOX @ MIL-On-MIL of example 2, the DOX @ NH of comparative example 12MIL-88B was subjected to light-shielded drug release experiments in PBS at pH 7.4, 6.5 and 5.0, respectively. Specifically, 3 mg of each of the samples of examples and comparative examples was taken and subjected to a sustained release experiment in 10 mL of PBS. Sucking a certain volume of supernatant at different time intervals (0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h and 18 h), centrifuging to remove possible trace precipitates, then supplementing the PBS with the extracted volume corresponding to the pH value, and moving the possible precipitates back to the sustained-release solution. And measuring the absorbance at the wavelength of 480 nm, and calculating the drug release amount according to the standard curve of the 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, and 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 22-MIL-88B was added separately with different concentrations of H2O2In PBS (pH = 4.0), DOX @ MIL-On-MIL and NH were compared using 3,3,5, 5-Tetramethylbenzidine (TMB)2Peroxidase-like (POD) activity of MIL-88B, the final concentrations of sample and TMB in the reaction system were 250. mu.g/mL and 1.0 mM, respectively. After 10 min incubation, the peroxidase-like activity was verified based on the intensity of the signal peak in the oxidation state of TMB (oxTMB) at 652 nm.
The results of the peroxidase-like activity assay are shown in FIG. 4, where it can be seen that DOX @ MIL-On-MIL still retains NH2Peroxidase-like activity inherent to MIL-88B.
5. DOX @ MIL-On-MIL from example 2 was added to a solution containing 1mM H2O2DOX @ MIL-On-MIL peroxidase-like (POD) activity was tested in different pH buffers using 3,3,5, 5-Tetramethylbenzidine (TMB) in PBS solutions at different pH concentrations (7.4, 6.5, 5.0, 4.0), with the final concentrations of sample and TMB in the reaction system being 250. mu.g/mL and 1.0 mM, respectively. Peroxidase-like activity at different pH's is shown in FIG. 5, from which it can be seen that DOX @ MIL-On-MIL after drug loading still has pH-responsive peroxidase-like activity under acidic conditions, and can be used for the chemokinetic treatment of cancer tissues.
6. Reacting NH2-MIL-88B，DOX@NH2-MIL-88B, DOX @ MIL-On-MIL and 4T1 cells were incubated together, and cell viability was calculated using the CCK-8 method. The results are shown in FIG. 6, NH at a maximum concentration of 100 ppm2After 24 hours of co-incubation of MIL-88B with cells, the cells still maintained high cell viability, indicating that the fe-based metal-organic framework material had good biocompatibility at a concentration of 100 ppm. After drug loading, DOX @ NH2MIL-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 the interaction with DOX @ NH2DOX @ MIL-On-MIL has a higher DOX drug load than MIL-88B. 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. ResultsThe method proves the material uptake behavior of cells, greatly meets the requirements of clinical application fields on various aspects of metal organic frameworks, and is beneficial to promoting the application progress of the metal organic framework materials 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 (10)

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 NH2Dispersing 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 by a solvothermal method.
2. The method of claim 1, wherein: NH (NH)2The mass ratio of the-MIL-88B, the 2-amino terephthalic acid and the ferric trichloride hexahydrate is 4-8:18: 27.
3. The method according to claim 1 or 2, characterized in that: NH (NH)2The concentration of-MIL-88B in absolute ethanol is 0.2-0.4 mg/mL.
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 NH2-MIL-88B is prepared by solvothermal method, ferric trichloride hexahydrate and organic ligand 2-amino terephthalic acid are ultrasonically dissolved inStirring and reacting in absolute ethyl alcohol at 35-45 ℃ for 1-2 hours, collecting a product after reaction, and washing to obtain NH2-MIL-88B。
6. The method according to claim 5, wherein: preparation of NH2When 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 MOF-On-MOF framework according to claim 7 as a carrier for a drug, preferably doxorubicin hydrochloride.
9. 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 NH2Dispersing MIL-88B in absolute ethyl alcohol containing a drug, then adding an organic ligand 2-amino terephthalic 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 by a solvothermal method.
10. The method of claim 9, wherein: the medicine is doxorubicin hydrochloride;
preferably, NH2-MIL-88B, 2-amino terephthalic acid and ferric chloride hexahydrate in a mass ratio of 4-8:18:27, the concentration of ferric chloride hexahydrate being 1-1.5 mg/mL;
preferably, NH2The mass ratio of MIL-88B to the medicine is 2-4: 5;
preferably, the reaction temperature of the solvothermal method is 35-45 ℃ and the reaction time is 1-2 hours.
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CN109616672A (en) * 2018-11-30 2019-04-12 安徽师范大学 Fe-N codope carbon material and its preparation method and application derived from ZIF-8@FeMOF
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CN109224085A (en) * 2018-09-11 2019-01-18 青岛大学 A kind of UCNPs@MIL-53 nanocomposite and preparation method thereof
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