CN113499430A - Fenton metal ion doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent, preparation method and application - Google Patents
Fenton metal ion doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent, preparation method and application Download PDFInfo
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Abstract
The invention discloses a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent, a preparation method and application. The nano diagnosis and treatment agent comprises: a Fenton metal ion doped metal-organic framework, an oxidative metabolizing enzyme immobilized on said Fenton metal ion doped metal-organic framework. The nano diagnosis and treatment agent is easy to degrade, has the characteristics of pH and glutathione response, and can release oxidative metabolism enzyme at a tumor part to interfere the energy metabolism of the tumor; the released Fenton metal ions have the characteristic of Fenton reaction in a tumor microenvironment and can decompose H at a tumor part2O2Generate hydroxyl free radical with strong oxidizing property, and enhance the treatment effect of tumor metabolism. The nano diagnosis and treatment agent has good dispersibility and uniform size, and the oxidative metabolism enzyme is solidified in the Fenton metal ion-doped metal-organic framework carrier, so that the problems of instability in vivo, blood toxicity and the like caused by direct exposure can be effectively avoided.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent, a preparation method and application.
Background
Enzymes involved in oxidative metabolism in organisms include glucose oxidase, lactate oxidase, thrombin, catalase, superoxide dismutase, and the like, have high catalytic activity and good biocompatibility, and have been developed for the treatment of various diseases, particularly tumor treatment by interfering with tumor metabolism. However, the application of free enzyme therapeutic agents in vivo has many problems, such as short half-life of blood circulation and easy inactivation. Some enzyme therapeutics may also cause systemic toxicity, e.g., glucose oxidase may catalyze the degradation of glucose in the blood to produce H2O2And reducing blood glucose concentration; thrombin initiates intravascular thrombosis and blocks the blood vessel. Therefore, oxidative metabolic enzymes cannot be directly convertedIs injected into the body.
The metal-organic framework (MOF) material is a coordination polymer which takes metal ions as connecting points and is supported by organic ligands to form spatial three-dimensional extension. The MOF material has a unique three-dimensional pore structure and is another important novel porous material besides zeolite and carbon nanotubes. In recent years, biocompatible and degradable MOF materials have received a great deal of attention in the biomedical field, and various biomedical MOF materials have been developed and applied to drug delivery and protein/enzyme immobilization. The defects of short blood circulation half-life, easy inactivation and in vivo toxicity of the enzyme therapeutic agent can be effectively avoided by fixing and transporting the enzyme therapeutic agent by the MOF material. Currently, the commonly used biomedical MOF materials are mainly zinc-based MOF materials such as ZIF-8, ZIF-90 and the like, however, the zinc-based MOF materials have less functions and are generally only used as carrier materials for transporting medicines, proteins/enzymes and genes.
Accordingly, the prior art remains to be improved and developed.
Disclosure of Invention
The inventor finds that similar to zinc element, elements such as manganese, copper, iron, cobalt, chromium, tungsten, aluminum, strontium and the like are also trace elements of human body, have important physiological action and can participate in normal metabolism of human body; meanwhile, manganese ions, copper ions, iron ions, cobalt ions, chromium ions, tungsten ions, aluminum ions and strontium ions can also be used as Fenton reagent and can be contacted with high-concentration H at tumor or inflammation part2O2The reaction generates active oxygen substances, thereby improving the treatment effect. Therefore, in the aspect of treatment of tumors and related diseases, the MOF material prepared by doping the metal ions (Fenton reagent) has greater advantages compared with the common zinc-based MOF material. Furthermore, there is no report in the literature on the use of uniform sized fenton reagent doped MOF materials for delivery of enzyme-like therapeutic agents for biomedical applications.
Based on the above, the invention aims to provide a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent, a preparation method and an application thereof, and aims to solve the problems of high blood toxicity and complex synthesis process of the existing enzyme-loaded nano diagnosis and treatment agent.
The technical scheme of the invention is as follows:
a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano-diagnosis and treatment agent, wherein the nano-diagnosis and treatment agent comprises: a Fenton metal ion doped metal-organic framework, an oxidative metabolizing enzyme immobilized on said Fenton metal ion doped metal-organic framework.
Optionally, the fenton metal ions are selected from one or more of manganese ions, copper ions, iron ions, cobalt ions, chromium ions, tungsten ions, aluminum ions, and strontium ions.
Optionally, the oxidative metabolic enzyme comprises one or more of glucose oxidase, lactate oxidase, thrombin, catalase, superoxide dismutase.
Optionally, the nano diagnosis and treatment agent has a hexagonal structure, the size of the nano diagnosis and treatment agent is uniform, and the size of the nano diagnosis and treatment agent is 10-500 nm.
Optionally, the metal-organic framework is a zinc-based MOF material.
The invention relates to a preparation method of a Fenton metal ion doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent, which comprises the following steps:
dissolving oxidative metabolism enzyme and 2-methylimidazole in water to prepare solution A;
dissolving zinc salt and Fenton metal salt in water to prepare solution B;
and adding the solution B into the solution A under stirring, and reacting to obtain the nano diagnosis and treatment agent.
Optionally, the molar concentration ratio of the fenton metal salt to the zinc salt is 0.01-1: 1.
Optionally, in the solution A, the concentration of the oxidative metabolism enzyme is 0.01-5 mg/mL.
Optionally, the step of adding the solution B into the solution a under stirring to react to obtain the nano diagnostic agent specifically includes: adding the solution B into the solution A under stirring, stirring at room temperature for 1 min-2 h, and performing centrifugal separation to obtain the nano diagnosis and treatment agent.
The invention relates to an application of a Fenton metal ion doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent in preparation of a tumor preparation.
The Fenton metal ion doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent is used as a drug or gene transport carrier.
Has the advantages that: the invention provides a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent for tumor metabolic therapy, wherein the nano diagnosis and treatment agent comprises a Fenton metal ion doped metal-organic framework material and oxidative metabolism enzyme immobilized on a porous Fenton metal ion doped metal-organic framework. The nano diagnosis and treatment agent provided by the invention is easy to degrade, has the characteristics of pH and glutathione response, and can release oxidative metabolism enzyme at a tumor part to interfere tumor energy metabolism; the released Fenton metal ions have the characteristic of Fenton reaction in a tumor microenvironment and can decompose H at a tumor part2O2Generate hydroxyl free radical with strong oxidizing property, and enhance the treatment effect of tumor metabolism. The nano diagnosis and treatment agent has good dispersibility and uniform size, and the oxidative metabolic enzyme is solidified in the Fenton metal ion-doped metal-organic framework carrier, so that the problems of instability in vivo, blood toxicity and the like caused by direct exposure can be effectively avoided. The preparation process of the nano diagnosis and treatment agent is simple, the operation is convenient, complex and expensive equipment is not needed, and the industrial production is easy to realize. The nano diagnosis and treatment agent can be used as a transport carrier of medicines and genes, can also be directly used as a tumor metabolism treatment medicine, and has good application prospect in the fields of medicine delivery, gene transfection, tissue repair, tumor diagnosis and treatment and the like.
Drawings
Fig. 1 is a flowchart of a method for preparing a nano diagnostic and therapeutic agent according to example 1;
FIG. 2 is an X-ray (XRD) diffractogram of the sample of example 1;
FIG. 3 is a Transmission Electron Microscope (TEM) photograph (a) and a Scanning Transmission Electron Microscope (STEM) photograph (b) of the sample of example 1;
FIG. 4 is the pH and Glutathione (GSH) response Cu of the samples of example 12+A release profile;
FIG. 5 shows the results of the catalytic activity measurements of the samples of example 1: reacting GOx @ CuMOF + glucose (Glu) + Glutathione (GSH) or GOx-MnCaP + Glu with the MB solution for different time to obtain the ultraviolet/visible absorption change condition of the MB solution; (c) the fluorescence spectrum of the solution after 0.5 millimole liter of TPA solution is respectively treated for 8 hours by different methods; (d) o in different solutions2A change in concentration. [ GOx @ CuMOF @]＝200μg/mL，[MB]＝5μg/mL，[GSH]＝10mM， [Glu]10mM ═ 10 mM; (e) detecting O in solution by JPBJ-608 portable dissolved oxygen tester (thunder magnet)2A graph of concentration change;
FIG. 6 is a TEM picture of a sample in example 2;
fig. 7 is a TEM picture of the sample in example 3.
Detailed Description
The invention provides a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent, a preparation method and application thereof, and the invention is further described in detail below in order to make the purpose, technical scheme and effect of the invention clearer and more clear. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The embodiment of the invention provides a Fenton metal ion doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent, wherein the nano diagnosis and treatment agent comprises: a fenton metal ion doped metal-organic framework, an oxidative metabolizing enzyme immobilized on said fenton metal ion doped metal-organic framework.
The embodiment provides a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent for tumor metabolic therapy, wherein the nano diagnosis and treatment agent comprises the Fenton metal ion doped metal-organic framework material and oxidation immobilized (combined) in pores or on the surface of a porous Fenton metal ion doped metal-organic frameworkA metabolic enzyme. The nano diagnosis and treatment agent provided by the embodiment is easy to degrade, has the characteristics of pH and glutathione response, and can release oxidative metabolic enzyme at a tumor part to interfere tumor energy metabolism; the released Fenton metal ions have the characteristic of Fenton reaction in a tumor microenvironment and can decompose H at a tumor part2O2Generate hydroxyl free radical with strong oxidizing property, and enhance the treatment effect of tumor metabolism. The nano diagnosis and treatment agent has good dispersibility and uniform size, and the oxidative metabolism enzyme is solidified in the Fenton metal ion-doped metal-organic framework carrier, so that the problems of instability in vivo, blood toxicity and the like caused by direct exposure can be effectively avoided. The preparation process of the nano diagnosis and treatment agent is simple, convenient to operate, free of complex and expensive equipment and easy to realize industrial production. The nano diagnosis and treatment agent can be used as a transport carrier of medicines and genes, can also be directly used as a tumor metabolism treatment medicine, and has good application prospects in the fields of medicine delivery, gene transfection, tissue repair, tumor diagnosis and treatment and the like.
In the embodiment, the nano diagnosis and treatment agent has a hexagonal structure, the size of the nano diagnosis and treatment agent is uniform, and the size of the nano diagnosis and treatment agent is 10-500 nm.
In one embodiment, the fenton metal ion is selected from one or more of manganese ion, copper ion, iron ion, cobalt ion, chromium ion, tungsten ion, aluminum ion, strontium ion, and the like.
In one embodiment, the oxidative metabolic enzyme comprises one or more of glucose oxidase, lactate oxidase, thrombin, catalase, superoxide dismutase, and the like.
In one embodiment, the metal-organic framework is a zinc-based MOF material, such as ZIF-8, ZIF-90, and the like.
The embodiment of the invention provides a preparation method of the Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent, which comprises the following steps:
s1, dissolving the oxidative metabolism enzyme and 2-methylimidazole in water to prepare a solution A;
s2, dissolving zinc salt and Fenton metal salt in water to prepare solution B;
and S3, adding the solution B into the solution A under stirring, and reacting to obtain the nano diagnosis and treatment agent.
The embodiment adopts oxidative metabolism enzyme, water-soluble fenton metal salt, water-soluble zinc salt and 2-methylimidazole as raw materials, water as a solvent, the oxidative metabolism enzyme and the 2-methylimidazole are dissolved in water to prepare a solution A, the water-soluble zinc salt and the water-soluble fenton metal salt are dissolved in water to prepare a solution B, then the solution B is added into the solution A under stirring, fenton metal ions, zinc ions and the 2-methylimidazole are coordinated to generate a hybridized metal-organic framework material through stirring at room temperature, and the oxidative metabolism enzyme is solidified in a porous hybridized metal-organic framework, so that the nano diagnosis and treatment agent of the oxidative metabolism enzyme solidified by the metal-organic framework material doped with the fenton metal ions is obtained.
The Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent prepared by the embodiment has a uniform size and a hexagonal structure, and the diameter of the nano diagnosis and treatment agent is 10-500 nm.
The embodiment has the following advantages:
(1) the obtained nano diagnosis and treatment agent is uniform in size and regular in appearance, and the size is 10-500 nm;
(2) the obtained nano diagnosis and treatment agent has good biocompatibility, can be used as a drug and gene delivery carrier, and can also be directly used as a tumor metabolism therapeutic agent.
The preparation method of the embodiment is simple in preparation process, convenient to operate, free of complex and expensive equipment and easy to realize industrial production. The Fenton metal ion-doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent prepared by the preparation method can be used as a transport carrier of medicines and genes, can also be directly used as a tumor metabolism treatment medicine, and has good application prospects in the fields of medicine delivery, gene transfection, tissue repair, tumor diagnosis and treatment and the like.
In step S1, in one embodiment, the oxidative metabolic enzyme is selected from one or more of glucose oxidase, lactate oxidase, thrombin, catalase, superoxide dismutase, and the like. The enzyme therapeutic agent has good biocompatibility and degradability, and does not bring toxic and side effects to the prepared nano therapeutic agent.
In one embodiment, the concentration of the oxidative metabolism enzyme in the solution A is 0.01-5 mg/mL. Further, in the solution A, the concentration of the oxidative metabolism enzyme is 0.1-1 mg/mL.
In one embodiment, the concentration of the 2-methylimidazole in the solution A is 0.1-1000 mg/mL. In step S2, the zinc salt in this embodiment is a water-soluble zinc salt. As the water-soluble zinc salt, zinc chloride and/or a hydrate thereof, zinc nitrate and/or a hydrate thereof, zinc sulfate and/or a hydrate thereof, and zinc acetate and/or a hydrate thereof, which are commonly used, can be used. The zinc salt is soluble and can be directly dissolved in water, so that water with wide sources and environmental friendliness can be selected as a solvent for the reaction.
In this embodiment, the fenton metal salt is a water-soluble fenton metal salt. The water-soluble fenton metal salt may be one or more selected from water-soluble manganese salts, water-soluble copper salts, water-soluble iron salts, water-soluble cobalt salts, water-soluble chromium salts, water-soluble tungsten salts, water-soluble aluminum salts, water-soluble strontium salts, and the like. The metal salts are soluble metal salts which can be directly dissolved in water, so that water with wide sources and environmental friendliness can be selected as a solvent for the reaction.
In one embodiment, the concentration of the water-soluble zinc salt in the solution B is 1-50 mM.
In one embodiment, the molar concentration ratio of the fenton metal salt to the zinc salt is 0.01 to 1: 1. further, the mol concentration ratio of the fenton metal salt to the zinc salt is 0.05-0.5: 1.
in one embodiment, step S3 specifically includes: adding 1.5mL of the solution B into 3.5mL of the solution A under stirring, stirring at room temperature for 1 min-2 h, coordinating Fenton metal ions, zinc ions and 2-methylimidazole through stirring at room temperature to generate a Fenton metal ion doped metal-organic framework material, and simultaneously solidifying the oxidative metabolism enzyme in the porous Fenton metal ion doped metal-organic framework. And (4) performing centrifugal separation on the product, wherein the separation method can comprise centrifugal separation, filtration or standing precipitation separation and the like. And washing, freeze-drying or vacuum-drying the separated product to obtain the Fenton metal ion-doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent.
The invention provides application of a Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent in preparation of a tumor preparation.
The Fenton metal ion doped metal-organic framework material nano diagnosis and treatment agent for immobilized oxidative metabolism enzyme provided by the embodiment of the invention is used as a drug or gene transport carrier.
The present invention will be described in further detail with reference to examples. It is also to be understood that the following examples are illustrative of the present invention and are not to be construed as limiting the scope of the invention, and that certain insubstantial modifications and adaptations of the invention by those skilled in the art may be made in light of the above teachings. For example, the following examples use Glucose Oxidase (GO)x) Or Lactate Oxidase (LO)x) As oxidative metabolism enzyme, Cu (NO)3)2Or MnCl2·4H2O as a water soluble Fenton metal salt, Zn (NO)3)·6H2O and 2-methylimidazole are used as starting materials, but other suitable water-soluble oxidative metabolizing enzymes, water-soluble Fenton metal salts and water-soluble zinc salts may be used instead, as described above. The specific reaction temperatures, times, amounts of charge, etc. of the following examples are also only one example of suitable ranges and are not intended to be limited to the specific values of the examples below.
Example 1
The Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent is prepared according to the steps of the attached figure 1, and the specific steps are as follows:
at room temperature, 2mg GOxAnd 770mg of 2-methylImidazole was dissolved in 3.5mL deionized water to form solution A, and 30mg Zn (NO) was added3)·6H2O and 6.3mg Cu (NO)3)2Dissolving the mixture in 1.5mL of deionized water to form a solution B, wherein the molar ratio of the copper salt to the zinc salt is 1: 3. adding the solution B into the solution A while stirring, stirring at room temperature for 5min, performing centrifugal separation, washing with deionized water for 3 times, and freeze-drying for 12h to obtain powder sample GOx@ CuMOF. In addition, control samples ZIF-8 and CuMOF were prepared as per Table 1.
TABLE 1
The X-ray diffraction pattern (XRD) of FIG. 2 shows that the obtained sample is crystalline and that the doping of copper ions and GOxThe loading of (a) has no significant effect on the phase of the MOF material.
The Transmission Electron Microscope (TEM) photograph shown in (a) of FIG. 3 shows that the obtained sample has a hexagonal structure and uniform size, and the size is 50-200 nm; the Scanning Transmission Electron Microscope (STEM) photograph shown in FIG. 3 (b) shows that the main elements of the obtained sample are C, N, O, S, Zn, Cu.
FIG. 4 is the GO prepared in this examplexDegradation of @ CuMOF in PBS at pH 7.4, 6.5 and PBS +10mM GSH solution at pH 7.4, 6.5. Detection of Cu in solution at different times by inductively coupled plasma emission spectrometry2+Ion concentration, results show Cu in solution at pH 6.52+Solutions with a concentration significantly higher than pH 7.4; and Cu in GSH-containing solution2+The concentration was significantly higher than the solution without GSH. The results demonstrate that GOx @ CuMOF prepared in this example has pH and GSH responsive degradation release characteristics.
GO prepared in this examplexThe @ CuMOF can mediate cascade catalytic reaction in tumor as shown in (a) in the attached figure 5, GOxCatalyzing oxidation of Glucose (Glu) in tumor to generate gluconic acid and H2O2And consumes O2(ii) a Released Cu2+Can eliminate the over expression in tumorGlutathione (GSH) of (D) is simultaneously reduced to Cu+；Cu+And H2O2A Fenton-like reaction occurs, producing OH to kill tumor cells. In FIG. 5, (b) and (c) show the degradation of Methylene Blue (MB) by the obtained sample, and the results show that in the presence of GSH and Glu, GOx @ CuMOF can effectively degrade MB.
In FIG. 5, (d) shows that OH is detected by terephthalic acid (TPA) oxidation, and the result shows that strong fluorescence can be detected in the solution in the presence of GSH and Glu, indicating that a large amount of OH is generated.
FIG. 5 (e) shows the detection of O in the solution by JPBJ-608 portable dissolved oxygen meter (Raymagnetic)2The concentration changes, and the results show that only the presence of Glu and GSH results in O in solution2The concentration decreases.
The above results show that the encapsulation of CuMOF can well protect GOxAnd after GSH is added, the GSH and Cu are added2+The redox reaction of equation (2) shown in (a) of FIG. 5 occurs in between, resulting in the destruction of CuMOF structure to release GOxThen, the reactions of equations (1) and (3) shown in (a) of FIG. 5 occur, resulting in MB degradation and TPA oxidation.
Example 2
At room temperature, 2mg GOxAnd 770mg of 2-methylimidazole in 3.5mL of deionized water to form solution A, and 30mg of Zn (NO)3)·6H2O and 7.2mg MnCl2·4H2Dissolving O in 1.5mL of deionized water to form a solution B, wherein the molar ratio of the manganese salt to the zinc salt is 1: 3. adding the solution B into the solution A while stirring, stirring at room temperature for 5min, performing centrifugal separation, washing with deionized water for 3 times, and freeze-drying for 12h to obtain powder sample GOx@MnMOF。
The TEM photograph of FIG. 6 shows that the obtained samples are mainly hexagonal structures, and a small number of the samples are circular structures with the size of 50-300 nm.
Example 3
0.5mg LO at room temperaturexAnd 770mg of 2-methylimidazole in 3.5mL of deionized water to form solution A, and 30mg of Zn (NO)3)·6H2O and 6.3mg Cu(NO3)2Dissolving the mixture in 1.5mL of deionized water to form a solution B, wherein the molar ratio of the copper salt to the zinc salt is 1: 3. adding the solution B into the solution A under stirring, stirring at room temperature for 5min, centrifuging, washing with deionized water for 3 times, and freeze drying for 12 hr to obtain powder sample LOx@CuMOF。
The TEM photograph of FIG. 7 shows that the obtained sample has a hexagonal structure with dimensions of 50-300 nm.
In summary, the present invention provides a nano diagnostic agent of immobilized oxidative metabolism enzyme of fenton metal ion doped metal-organic framework material, and a preparation method and an application thereof, wherein the nano diagnostic agent comprises the fenton metal ion doped metal-organic framework material and the oxidative metabolism enzyme immobilized in the porous fenton metal ion doped metal-organic framework. The nano diagnosis and treatment agent provided by the invention is easy to degrade, has the characteristics of pH and glutathione response, and can release oxidative metabolism enzyme at a tumor part to interfere the energy metabolism of the tumor; the released Fenton metal ions have the characteristic of Fenton reaction in a tumor microenvironment and can decompose H at a tumor part2O2Generate hydroxyl free radical with strong oxidizing property, and enhance the curative effect of tumor metabolism. The nano diagnosis and treatment agent prepared by the invention has good dispersibility and uniform size, and the oxidative metabolic enzyme is solidified in the Fenton metal ion-doped metal-organic framework carrier, so that the problems of in vivo instability, blood toxicity and the like caused by direct exposure can be effectively avoided. The preparation process of the nano diagnosis and treatment agent is simple, the operation is convenient, complex and expensive equipment is not needed, and the industrial production is easy to realize. The nano diagnosis and treatment agent prepared by the invention can be used as a transport carrier of medicines and genes, can also be directly used as a tumor metabolism treatment medicine, and has good application prospect in the fields of medicine delivery, gene transfection, tissue repair, tumor diagnosis and treatment and the like.
It is to be understood that the invention is not limited to the examples described above, but that modifications and variations may be effected thereto by those of ordinary skill in the art in light of the foregoing description, and that all such modifications and variations are intended to be within the scope of the invention as defined by the appended claims.
Claims (10)
1. A Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent is characterized by comprising the following components in parts by weight: a Fenton metal ion doped metal-organic framework, an oxidative metabolizing enzyme immobilized on said Fenton metal ion doped metal-organic framework.
2. The Fenton's metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnostic agent according to claim 1, wherein the Fenton's metal ion is selected from one or more of manganese ion, copper ion, iron ion, cobalt ion, chromium ion, tungsten ion, aluminum ion and strontium ion.
3. The Fenton's metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnostic agent according to claim 1, wherein the oxidative metabolism enzyme comprises one or more of glucose oxidase, lactate oxidase, thrombin, catalase, superoxide dismutase.
4. The Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent according to claim 1, wherein the nano diagnosis and treatment agent has a hexagonal structure, the size of the nano diagnosis and treatment agent is uniform, and the size of the nano diagnosis and treatment agent is 10-500 nm.
5. The Fenton metal ion doped metal-organic framework material immobilized oxidative metabolic enzyme nano diagnostic agent according to claim 1, characterized in that the metal-organic framework is a zinc-based MOF material.
6. A preparation method of the Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent as claimed in any one of claims 1 to 5, which is characterized by comprising the following steps:
dissolving oxidative metabolism enzyme and 2-methylimidazole in water to prepare solution A;
dissolving zinc salt and Fenton metal salt in water to prepare solution B;
and adding the solution B into the solution A under stirring, and reacting to obtain the nano diagnosis and treatment agent.
7. The method for preparing the Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent according to claim 6, wherein the molar concentration ratio of the Fenton metal salt to the zinc salt is 0.01-1: 1.
8. the method for preparing the Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent according to claim 6, wherein the concentration of the oxidative metabolism enzyme in the solution A is 0.01-5 mg/mL.
9. The method for preparing the Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent according to claim 6, wherein the step of adding the solution B into the solution A under stirring to react to obtain the nano diagnosis and treatment agent comprises the following steps: adding the solution B into the solution A under stirring, stirring at room temperature for 1 min-2 h, and performing centrifugal separation to obtain the nano diagnosis and treatment agent.
10. The application of the Fenton metal ion-doped metal-organic framework material solidified oxidative metabolism enzyme nano diagnosis and treatment agent as claimed in any one of claims 1 to 5 in preparation of tumor preparations;
or, the Fenton metal ion doped metal-organic framework material immobilized oxidative metabolism enzyme nano diagnosis and treatment agent as claimed in any one of claims 1 to 5 is used as a drug or gene transport carrier.
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