Amorphous metal coordination polymer hollow multi-shell structure material, preparation method thereof and application of amorphous metal coordination polymer hollow multi-shell structure material in field of slow release of anticancer drugs

Abstract

The invention relates to an amorphous metal coordination polymer hollow multi-shell structure material, a preparation method thereof and application of the amorphous metal coordination polymer hollow multi-shell structure material in anti-cancer drug carriers. According to the method, a metal organic framework in which metal ions are uniformly distributed is used as a template, an alkaline solution is added in a liquid phase environment to trigger template dissolution and shell polymerization, ligand exchange and dissolution rates are accurately controlled, and a shell growth rate is adjusted; therefore, the amorphous metal coordination polymer hollow multi-shell structure material formed by co-coordination of metal ions, high-molecular polymers and organic ligands is prepared in one step. The material has high anticancer drug loading capacity, excellent biocompatibility and acid response drug release performance, and has an excellent application prospect in the aspect of anticancer drug slow release.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of functional materials, in particular to a hollow multi-shell material of amorphous metal coordination polymer and a preparation method and application thereof. BACKGROUND

[0002] Rational design of the structure of nanomaterials can endow them with unique physical and chemical properties, thereby improving their performance in current application fields. Hollow multi-shell structure (HoMS) has multiple shell layers (shell layer number ≥ 2) arranged in order from the outside to the inside and closed cavities separated by shell layers and independently connected to each other. This unique structure makes the material have the advantages of large specific surface area, light density and time-space sequence, and has a wide application prospect in the fields of cascade catalysis, drug sequential release, photocatalysis, etc. Due to the excellent performance brought by the unique structure of HoMS material, the composition control of HoMS material has also attracted much attention, including metals, metal oxides, metal sulfides, metal organic framework compounds (MOF) and polymer materials, etc.

[0003] Among the numerous chemical compositions, the HoMS material of amorphous metal coordination polymer combines the advantages of organic materials and inorganic materials, and has a wide application prospect in the fields of drug release, disease treatment and biosensing, etc. Although inorganic materials have the advantages of easy functionalization and good catalytic activity, their poor colloidal stability and poor biocompatibility limit their further application. The hollow multi-shell material of amorphous metal coordination polymer combines the advantages of good biocompatibility of organic materials and high catalytic activity of inorganic materials. The rich functional groups of the organic part can form π-π bond, hydrogen bond and other interactions with drug molecules, thereby improving the loading capacity of drug molecules. The inorganic part has excellent catalytic activity and can catalyze the reaction of generating reactive oxygen species (ROS) from hydrogen peroxide (H2O2) to promote tumor ablation, thereby realizing multifunctional and multi-method disease treatment.

[0004] For the synthesis of amorphous metal coordination polymer HoMS, the commonly used strategy is to use hard template method to prepare single-shell amorphous metal coordination polymer hollow material. The specific implementation method is to use high molecular polymer or resin micro-nano particles as a template, generate amorphous metal coordination polymer on the surface thereof, and obtain uniform hollow material by etching the template. However, it is difficult to realize the preparation of amorphous metal coordination polymer HoMS with two shells and more. Therefore, the inventors propose a method for preparing amorphous metal coordination polymer HoMS in a liquid phase in the present application, and prepare amorphous metal coordination polymer hollow multi-shell structure material composed of metal ions, high molecular polymer and organic ligand. Such material has high drug loading capacity, excellent biocompatibility and acid-responsive drug release performance, so that it has excellent application prospect in the slow release of anticancer drugs. Through continuous research and innovation, the amorphous metal coordination polymer HoMS material is expected to play a greater role in the medical field and make contributions to human health and scientific and technological development. SUMMARY

[0005] In order to solve the technical problems existing in the prior art, the purpose of the present application is to provide a preparation method for synthesizing amorphous metal coordination polymer HoMS material in a liquid phase environment, and successfully applied to the slow release of anticancer drugs such as doxorubicin, paclitaxel and cisplatin.

[0006] The first object of the present application provides an amorphous metal coordination polymer HoMS material, which is characterized in that the material is composed of metal ions, high molecular polymer and organic ligand, and the size is micron level, and the morphology includes microspheres, hexahedron, hexagonal bipyramid, octahedron and dodecahedron, and the number of shell layers is 1-3.

[0007] The metal ion part of the material is any one of Fe, Co, Zr, Cr or Zn, the polymer part is a high molecular polymer polymerized by phenol and aldehyde, the phenol can be a combination of one or more of phenol, o-dihydroxybenzene, m-dihydroxybenzene, p-dihydroxybenzene, 3-aminophenol or natural polyphenol such as tannic acid, and the aldehyde is formaldehyde, acetaldehyde or a mixture of the two. The metal element is coordinated with the phenolic hydroxyl group and uniformly fixed in the structure.

[0008] The second object of the present application provides a ligand exchange reaction of metal ions and organic phenol in a liquid phase environment, so as to replace the organic ligand of the template itself, and prepare amorphous metal coordination polymer hollow multi-shell structure material in one step.

[0009] The method comprises: using MOF as a template, constructing a ligand exchange reaction of metal ions and organic phenol in a liquid phase environment to replace the organic ligand of the template itself, using two different organic ligands to control the stability of the template and regulate the ligand exchange speed during the synthesis process, thereby preparing a single, double, and triple-shell hollow multi-shell structure in one step, and finally stabilizing the shell structure through a polymerization reaction of organic phenol and aldehyde to obtain an amorphous metal coordination polymer hollow multi-shell structure material composed of metal ions, polymer and organic ligand coordination.

[0010] The template stability regulation method is to simultaneously add two organic ligands during the synthesis of MOF, to regulate the defect concentration of MOF itself by adjusting the ratio of the organic ligands, and to further regulate the stability of the template itself.

[0011] The specific method is to dissolve a metal salt and two organic ligands in a solvent. The solvent can be N,N-dimethylformamide, ethanol, water, methanol, acetonitrile or a mixture thereof; the metal salt can be one of nitrate, chloride or acetate of iron, zinc, chromium, zirconium and cobalt; and the organic ligand is a combination of one of terephthalic acid, 2-methyl imidazole, tetra(4-carboxyphenyl)porphyrin and one of fumaric acid, benzoic acid, acetic acid, trifluoroacetic acid. The above solution is placed in a reaction kettle and heated for a period of time, the heating temperature is 20-300℃, preferably 100-180℃, and the hydrothermal time is 1-12h, preferably 6-12h.

[0012] The obtained MOF template species can be one of MOF-235, MOF-5, MIL-88B, MIL-101(Cr), UiO-66, PCN-223, ZIF-67 or ZIF-8, and the particle size distribution is 0.1-2μm.

[0013] The above MOF template is uniformly dispersed in a solvent, which is a mixture of water and ethanol with a ratio of 1:5 to 5:1. Then a phenolic resin precursor is dissolved in the solution, wherein the phenolic resin precursor, the phenol can be a combination of one or more of catechol, resorcinol, hydroquinone, 3-aminophenol and natural polyphenols such as tannic acid, and the aldehyde can be formaldehyde, acetaldehyde or a mixture of the two, and the molar ratio of phenol to aldehyde is 1:1 to 1:6. Then a basic solution is slowly added, the base can be inorganic bases such as ammonia, sodium hydroxide, potassium hydroxide and organic bases such as dibutylammonium hydroxide, etc., and the amount added is 4-20mmol. After stirring at a certain temperature for a period of time, a hollow multi-shell structure of amorphous metal coordination polymer is obtained. The reaction temperature can be 30-80℃, and the reaction time is 1-12h. The precipitate is filtered, washed, dried and cooled to obtain the final product. The washing solvent is ethanol, and the washing times are 3-5 times; the drying temperature is 60-80℃, and the drying time is 12h.

[0014] The third object of the present application provides a drug loading method of amorphous metal coordination polymer HoMS material.

[0015] The method places the amorphous metal coordination polymer HoMS material in a round-bottom flask, injects an anticancer drug solution into the flask after vacuumizing for 30 min, and the type of the anticancer drug can be one of doxorubicin, paclitaxel and cisplatin. Stirring is performed at a certain temperature for 1-24 h, and the stirring temperature is 0-80℃. After the stirring is completed, the powder is washed by centrifugation with deionized water for three times, and freeze-drying is performed. The above operation is repeated three times, and the amorphous metal coordination polymer HoMS material loaded with the anticancer drug is successfully obtained.

[0016] The fourth object of the present application provides the application of the amorphous metal coordination polymer hollow multi-shell structure material in the field of anticancer drug sustained release. The material is placed in a PBS solution with pH 5.0 to achieve accurate release of the anticancer drug under acidic conditions. The material has high drug loading capacity and excellent biocompatibility, and has excellent application prospect in the field of anticancer drug sustained release.

[0017] Compared with the related art known to the present inventors, one of the technical solutions of the present application has the following beneficial effects:

[0018] (1) The present application provides a method for controlling the structure of MOF template, which realizes the control of the removal speed of the template and the generation speed of the shell layer in the later liquid phase reaction. The method specifically controls the stability of the MOF template structure by controlling the type of ligand, the type of solvent, the reaction time and the reaction temperature in the synthesis process of the MOF template.

[0019] (2) The present application provides a method for preparing amorphous metal coordination polymer HoMS material in one step under mild conditions and with simple operation. The ligand exchange reaction between metal ions and organic phenol is constructed in a liquid phase environment, so as to replace the organic ligand of the template itself. The stability of the template is controlled by using two different organic ligands in the synthesis process, the ligand exchange speed is controlled, and the amorphous metal coordination polymer HoMS with different shell layer numbers is directly synthesized in a liquid phase environment. The structure is composed of amorphous metal coordination polymer with uniform distribution of metal ions, which is further stabilized by the polymerization reaction of organic phenol and aldehyde.

[0020] (3) The preparation method of the amorphous metal coordination polymer HoMS material of the present application is simple in operation, mild in reaction condition, short in reaction time, does not need high temperature and oil bath, and directly prepares single, double and triple shell layer amorphous metal coordination polymer HoMS material in one step.

[0021] (4) The amorphous metal coordination polymer HoMS material of the present application successfully loads anticancer drugs through the method of multiple vacuum washing and has a high loading capacity. The amorphous metal coordination polymer HoMS material after loading anticancer drugs realizes acid-responsive drug release in the drug release of anticancer drugs, so as to precisely control the release of drug molecules around tumor cells and reduce the toxicity to normal cells, and inhibit the growth of tumor cells. BRIEF DESCRIPTION OF DRAWINGS

[0022] The drawings accompanying the specification of this application form a part thereof, serve to provide further understanding of the application, and together with the description of the exemplary embodiments of the application, serve to explain the application, and do not constitute an improper limitation on the application.

[0023] Figure 1 It is a transmission electron microscope image of the three-shell Fe-resorcinol amorphous metal coordination polymer HoMS material (3S-Fe-R-HoMS) in the present application.

[0024] Figure 2 It is a synchrotron radiation curve of the three-shell Fe-resorcinol amorphous metal coordination polymer HoMS material (3S-Fe-R-HoMS) in the present application.

[0025] Figure 3 It is an infrared spectrum of the three-shell Fe-resorcinol amorphous metal coordination polymer HoMS material (3S-Fe-R-HoMS) in the present application.

[0026] Figure 4 It is a drug release curve of the Fe-resorcinol amorphous metal coordination polymer HoMS material (3S-Fe-R-HoMS) in the present application. DETAILED DESCRIPTION

[0027] As introduced in the background, there is only a method of preparing hollow amorphous metal coordination polymer material by using hard template method at present, and there is no method of preparing amorphous metal coordination polymer HoMS material. In order to solve the above technical problems, in the first typical embodiment of the present application, a preparation method of synthesizing amorphous metal coordination polymer HoMS material in a liquid phase environment is provided. The material is an amorphous metal coordination polymer HoMS material which is coordinated by metal ions and organic ligands, and is stable after polymer growth.

[0028] In one or more embodiments of the present application, the metal organic framework material, abbreviated as MOF, is an organic-inorganic hybrid material with intramolecular pores formed by self-assembly of organic ligands and metal ions or clusters through coordination bonds.

[0029] In one or more embodiments of the present application, the size (e.g. particle size) of the metal organic framework material MOF is about 0.1-2 μm.

[0030] In one or more embodiments of the present application, a method for regulating the structure of MOF template is provided, which realizes the regulation of the template decomposition rate and shell formation rate in the later liquid phase reaction. The method comprises: regulating the type of ligand, the type of solvent, the reaction time and the reaction temperature in the synthesis process of the MOF template to realize the regulation of the structural stability of the MOF template.

[0031] In one or more embodiments of the present application, a preparation method of an amorphous metal coordination polymer HoMS material is provided, which comprises:

[0032] (1) placing the MOF template in a mixed solution of water / ethanol, adding a phenolic resin precursor, and stirring at a certain temperature for a period of time;

[0033] (2) centrifugal washing to obtain a powder product.

[0034] In step (1), the MOF template is one of MOF-235, MOF-5, MIL-88B, MIL-101(Cr), UiO-66, PCN-223, ZIF-67 and ZIF-8; the ratio of water to ethanol in the mixed solution is 1:5 to 5:1; the heating temperature is 30-80℃; and the stirring time is 1-12h.

[0035] In a sixth typical embodiment of the present disclosure, the application of the amorphous metal coordination polymer HoMS material in the sustained release of anticancer drugs such as doxorubicin, paclitaxel, cisplatin and the like is provided.

[0036] In order to enable those skilled in the art to more clearly understand the technical solutions of the present disclosure, the technical solutions of the present disclosure will be described in detail below in combination with specific examples.

[0037] Example 1

[0038] The synthesis of the single-shell Fe-resorcinol amorphous metal coordination polymer material (1S-Fe-R-HS) comprises the following steps:

[0039] (1) Template synthesis

[0040] 5 mmol of anhydrous iron chloride was placed in 30 mL of N,N-dimethylformamide, 100 mg of benzoic acid and 100 mg of terephthalic acid were added and stirred uniformly. The mixed solution was placed in a reaction kettle, the oven temperature was set to 180℃, and the hydrothermal reaction was carried out for 6h. After the reaction kettle was naturally cooled, it was subjected to suction filtration and washing, and the product was placed in a 70℃ oven for drying overnight to obtain the template.

[0041] (2) Synthesis of 1S-Fe-R-HS

[0042] 20 mg of the template was added to a 14 mL mixture of ethanol and water and dispersed evenly by ultrasonication. Then, 0.3 mmol of resorcinol and 0.6 mmol of formaldehyde were added dropwise, followed by 4 mmol of aqueous ammonia. The mixture was allowed to react at 30°C for 4 hours. The resulting solid particles were filtered, washed three times with ethanol, and then oven-dried at 70°C for 12 hours. This yielded a reddish-brown powder of 1S-Fe-R-HS.

[0043] Example 2

[0044] The synthesis of a three-shell Fe-resorcinol amorphous metal coordination polymer hollow multi-shell structure (3S-Fe-R-HoMS) comprises the following steps:

[0045] (1) Template synthesis

[0046] 5 mmol of anhydrous ferric chloride was placed in 30 mL of a 1:1 mixture of N,N-dimethylformamide and ethanol. 100 mg of benzoic acid and 100 mg of terephthalic acid were added and stirred thoroughly. The mixed solution was placed in a reactor and set to an oven temperature of 130°C for a hydrothermal reaction for 12 hours. After the reactor was removed from the reactor and cooled naturally, the product was filtered and washed. The product was then dried in a 50°C oven overnight to obtain the template.

[0047] (2) Synthesis of 3S-Fe-R-HoMS

[0048] 20 mg of the template was added to a 14 mL mixture of ethanol and water and dispersed evenly by ultrasonication. Then, 0.3 mmol of resorcinol and 0.6 mmol of formaldehyde were added dropwise, followed by 4 mmol of aqueous ammonia. The mixture was allowed to react at 30°C for 4 hours. The resulting solid particles were filtered, washed three times with ethanol, and then oven-dried at 70°C for 12 hours. This yielded a reddish-brown powder of the single 3S-Fe-R-HoMS.

[0049] (4) Results

[0050] like Figure 1 As shown, the diameter of 3S-Fe-R-HoMS is about 400 nm.

[0051] like Figure 2 As shown, the Fe element in 3S-Fe-R-HoMS is coordinated with resorcinol and thus fixed in the structure.

[0052] like Figure 3 As shown in the figure, 3S-Fe-R-HoMS has obvious characteristic peaks of phenolic resin, indicating that the material is an amorphous polymer coordinated by Fe and resorcinol.

[0053] Example 3

[0054] Synthesis of double-shell Fe-3-aminophenol amorphous metal coordination polymer hollow multi-shell structure (2S-Fe-AR-HoMS) including the following steps:

[0055] (1) Template synthesis

[0056] 5 mmol of anhydrous iron chloride was placed in 30 mL of N,N-dimethylformamide, 100 mg of benzoic acid and 100 mg of terephthalic acid were added and stirred uniformly. The mixed solution was placed in a reaction kettle, the oven temperature was set to 150°C, and the hydrothermal reaction was carried out for 6 h. After the reaction kettle was naturally cooled, it was subjected to suction filtration and washing. The product was placed in a 60°C oven and dried overnight to obtain the template.

[0057] (2) Synthesis of 2S-Fe-AR-HoMS

[0058] 20 mg of the template was added to a mixed solution of 14 mL of ethanol and water and ultrasonically dispersed uniformly. Then 0.3 mmol of 3-aminophenol and 0.6 mmol of formaldehyde were added, and finally 10 mmol of ammonia water was added dropwise, and the reaction was carried out at 20°C for 4 h. The obtained solid particles were filtered, washed with ethanol for 3 times, and then placed in a 70°C oven for 12 hours. Finally, the 2S-Fe-AR-HoMS red-brown powder was obtained.

[0059] Example 4

[0060] Synthesis of single-shell Zn-3-aminophenol amorphous metal coordination polymer hollow multi-shell structure (1S-Zn-AR-HoMS) including the following steps:

[0061] (1) Template synthesis

[0062] 5 mmol of Zn(NO3)2 was placed in 30 mL of deionized water, 5 mmol of 2-methyl imidazole and 5 mmol of trifluoroacetic acid were added and stirred uniformly, and the mixture was stirred at 30°C for 12 h. The obtained product was subjected to suction filtration and washing, and the product was placed in a 60°C oven and dried overnight to obtain the template.

[0063] (2) Synthesis of 1S-Zn-AR-HoMS

[0064] 20 mg of the template was added to a mixed solution of 14 mL of ethanol and water and ultrasonically dispersed uniformly. Then 0.3 mmol of 3-aminophenol and 0.6 mmol of formaldehyde were added, and finally 10 mmol L of ammonia water was added dropwise, and the reaction was carried out at 20°C for 4 h. The obtained solid particles were filtered, washed with ethanol for 3 times, and then placed in a 70°C oven for 12 hours. Finally, the 1S-Zn-AR-HoMS red-brown powder was obtained.

[0065] Example 5

[0066] Synthesis of single-shell Zn-tannic acid amorphous metal coordination polymer hollow multi-shell structure (1S-Zn-TA-HoMS) including the following steps:

[0067] (1) Template synthesis

[0068] 5 mmol of Zn(N03)2 was placed in 30 mL of deionized water, 5 mmol of 2-methylimidazole and 5 mmol of trifluoroacetic acid were added and stirred uniformly, and the obtained product was stirred at 30°C for 12 h. The obtained product was filtered and washed, and the product was placed in a 60°C oven and dried overnight to obtain the template.

[0069] (2) Synthesis of 1S-Zn-AR-HoMS

[0070] 20 mg of the template was added to a mixed solution of 14 mL of ethanol and water and ultrasonically dispersed uniformly. Then, 0.1 mmol of tannic acid and 0.6 mmol of formaldehyde were added, and finally 5 mmol of potassium hydroxide was added dropwise, and the reaction was carried out at 80°C for 4 h. The obtained solid particles were filtered and washed with ethanol three times, and then placed in a 70°C oven for 12 hours. Finally, a reddish-brown powder of 1S-Zn-TA-HoMS was obtained.

[0071] Example 6

[0072] (1) Doxorubicin loading

[0073] First, 10 mg of 3S-Fe-R-HoMS material was placed in a double-necked flask, and then vacuumed for half an hour. Second, 3 mL of a PBS solution of doxorubicin with pH = 7.4 was added to the flask using a syringe, and stirred at 30°C for 3 h. In the third step, the powder was centrifuged and washed with a PBS solution with pH = 7.4 three times. Finally, the solid powder was freeze-dried. The above operation was repeated three times to obtain doxorubicin-loaded 3S-Fe-R-HoMS. All these operations were carried out in the dark. The final loading amount of doxorubicin was measured by a UV-visible spectrophotometer.

[0074] (2) Drug release performance

[0075] 2 mg of doxorubicin-loaded material was placed in 60 mL of PBS solution with different pH values (pH 7.4 or 5.0). Every certain time, 6 mL of supernatant was centrifuged and replaced with 6 mL of PBS solution. The release amount of doxorubicin was determined by the absorbance of the supernatant.

[0076] (3) Structure

[0077] Figure 4As shown, the Fe-R-HoMS material has excellent pH response performance, realizes drug burst release under acidic conditions, and the pH response release amount of the three-shell layer material within 24 hours is 2 times and 1.5 times that of the single-shell layer and double-shell layer materials, respectively.

[0078] In this paper, the template decomposition rate and the shell formation rate are matched in a liquid phase environment, and the hollow multi-shell structure material of amorphous metal coordination polymer is prepared in one step. By controlling the ligand exchange and ligand dissolution rate, the hollow multi-shell structure of amorphous metal coordination polymer with different shells is realized in a one-step liquid phase system. The structure is a hollow multi-shell structure of amorphous metal coordination polymer with uniform distribution of metal ions, which is coordinated by metal ions and organic ligands, and further stabilized by polymerization reaction to realize the skeleton structure. The material has excellent acid-responsive drug release characteristics, and the pH response release amount of the three-shell layer material within 24 hours is 2 times and 1.5 times that of the single-shell layer and double-shell, respectively.

[0079] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. An amorphous metal coordination polymer hollow multi-shell structure material, characterized by The invention relates to an amorphous metal coordination polymer hollow multi-shell structure material in which metal ions are coordinated with organic ligands and then stabilized after polymer growth. The metal ion portion of the material is any one of Fe, Co, Zr, Cr or Zn, and the polymer portion is a high molecular weight polymer generated by the polymerization of phenol and aldehyde, wherein the phenol is a combination of one or more of phenol, catechol, resorcinol, hydroquinone, 3-aminophenol or natural polyphenols such as tannic acid, and the aldehyde is formaldehyde or acetaldehyde or a mixture of the two.

2. The amorphous metal coordination polymer hollow multi-shell structure material according to claim 1, wherein: The number of shells is 1-3, their size is micrometer-level, and their morphologies include microspheres, hexahedrons, hexagonal bipyramids, octahedrons, and dodecahedrons.

3. A method for preparing an amorphous metal coordination polymer hollow multi-shell structure material in a liquid phase, characterized by By constructing a ligand exchange reaction between metal ions and organic phenols in a liquid environment to replace the organic ligands of the template itself, the template stability is regulated to control the ligand exchange rate, and single-, double-, and triple-shell hollow multi-shell structures are prepared in one step. Finally, the shell structure is stabilized by a polymer polymerization reaction of organic phenols and aldehydes to obtain an amorphous metal coordination polymer hollow multi-shell structure material composed of metal ions, high molecular polymers and organic ligands.

4. The method for preparing the amorphous metal coordination polymer hollow multi-shell structure material according to claim 3, comprising the following steps: (1) Dissolving the metal salt and two organic ligands in a solvent and subjecting them to a hydrothermal reaction for a certain period of time to synthesize a uniform MOF template; (2) The MOF template is uniformly dispersed in a solvent, and the phenolic resin precursor is dissolved therein, Then slowly add alkaline solution dropwise and stir; (3) Filter, wash, dry and cool the precipitate to obtain the final product.

5. The method for preparing the amorphous metal coordination polymer hollow multi-shell structure material according to claim 4, characterized in that: In step (1), the metal salt is one of nitrates, chlorides or acetates of iron, zinc, chromium, zirconium or cobalt; In step (1), two organic ligands, one of which is terephthalic acid, 2-methylimidazole or tetrakis(4-carboxyphenyl)porphyrin, and the other is fumaric acid, benzoic acid, acetic acid or trifluoroacetic acid; In step (1), the solvent is N,N-dimethylformamide, ethanol, water, methanol, acetonitrile or a mixture thereof; In step (1), the heating temperature is 20-300°C, preferably 100-180°C; In step (1), the holding time is 1 to 12 hours, preferably 6 to 12 hours; In step (2), the MOF template is one of MOF-235, MOF-5, MIL-88B, MIL-101(Cr), UiO-66, PCN-223, ZIF-67 or ZIF-8, and has a particle size distribution of 0.1 to 2 μm; In step (2), the solvent is a mixed solvent of water and ethanol in a volume ratio of 1:5 to 5:1; In step (2), the phenolic resin precursor, wherein the phenol is a combination of one or more of phenol, catechol, resorcinol, hydroquinone, 3-aminophenol or natural polyphenols such as tannic acid; the aldehyde is formaldehyde or acetaldehyde or a mixture of the two, and the molar ratio of phenol to aldehyde is 1:1 to 1:6; In step (2), the alkaline solution uses an inorganic base such as ammonia, sodium hydroxide, potassium hydroxide or an organic base such as dibutylammonium hydroxide, and the addition amount is 4-20 mmol; In step (2), the stirring temperature is 30 to 80° C., and the stirring time is 1 to 12 h; In step (3), the washing solvent is ethanol, and the number of washing times is 3-5 times; In step (3), the drying temperature is 60-80° C. and the drying time is 12 h.

6. A material loaded with anticancer drugs, characterized in that: The amorphous metal coordination polymer hollow multi-shell structure material according to claim 1 or 2 is used as a drug carrier, and the loaded anticancer drug is doxorubicin, paclitaxel or cisplatin.

7. Use of the anticancer drug-loaded material according to claim 6 in the field of sustained release of anticancer drugs, characterized in that: The material has high drug loading capacity, excellent biocompatibility and acid-responsive drug release performance, and can achieve precise release of anticancer drugs.

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