Preparation and application of a kind of antimony tungsten acid material with catalytic fenton reaction activity

Abstract

The application discloses preparation and application of a kind of antimony tungstate material with catalytic Fenton reaction activity, the molecular formula of the antimony tungstate material is H 11 [Ln2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O, abbreviated as 1-Ln, wherein Ln=Dy, Ho, Er, Tm, Y, Yb or Lu;DMF=N or N-dimethylformamide;The crystal structure of the antimony tungstate material is that two three-defect {B-alpha-SbW9O 33} units sandwich one four-core heterometallic cluster {Sb2Ln2O 10 (DMF)2} and one {W7O 29 (OH)} cluster unit to form a high 1.9nm capsule-like isolated cluster structure, which has good water solubility and stability under physiological conditions.The antimony tungstate material with catalytic Fenton reaction activity can generate a large number of ·OH to kill cancer cells by catalyzing H2O2 decomposition and consuming glutathione through Fenton-like reaction, has high cytotoxicity and selectivity to various cancer cells, can significantly inhibit the growth of tumor in vivo, has small toxic and side effects to normal cells and organs, and can be used as an antitumor drug, applied to the field of biological medicine.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of drug synthesis, and particularly relates to preparation and application of a kind of antimony tungsten acid material with catalytic Fenton reaction activity. BACKGROUND

[0002] Cancer is still a malignant disease with high morbidity and mortality worldwide. In order to avoid the limitations of traditional cancer therapy, various minimally invasive cancer treatment strategies have been developed. As an alternative to traditional cancer therapy, chemical dynamics therapy (CDT) uses CDT agents to produce reactive oxygen species (ROS) through Fenton catalytic reaction to kill tumor cells quickly and efficiently, and is one of the cancer treatment strategies that has attracted much attention. In addition, the acidic microenvironment and relatively high concentration of H2O2 in tumor tissue are extremely beneficial to CDT compared with normal tissue. The commonly used CDT agent is iron-based and other metal-based nanomaterials with Fenton catalytic reaction activity. However, these iron-containing inorganic nanomaterials generally have poor water solubility, are not biodegradable, have long tissue residence time and slow elimination, etc. Therefore, it is urgent to develop CDT reagents with water solubility and biodegradability to achieve satisfactory anticancer effect.

[0003] Polyoxometalates (POMs) are also called polyacids, which are usually inorganic oxyacid salts of high-valent transition metals such as V, Nb, Ta, Mo and W, and form polynuclear metal cluster structures through polycondensation and dehydration. They have rich structure types, adjustable structure and size, excellent redox activity and good biocompatibility. Studies have found that polyacid materials can inhibit tumor development by damaging key processes of tumor cell division, thus having the efficacy of chemotherapy drugs. Compared with traditional chemotherapy, CDT takes advantage of the characteristics of tumor microenvironment (TME) to achieve high selectivity, and the oxidative stress induced by CDT can kill tumor cells through various pathways such as lipid peroxidation, DNA / RNA strand breakage, protein side chain oxidative modification and cell membrane damage. Considering its adjustable size and reversible redox properties, polyacids can also be used as a potential CDT reagent to react with H2O2 in TME through Fenton-like reaction to generate strong oxidizing and highly toxic hydroxyl radicals (·OH), further inducing apoptosis and inhibiting tumor growth. Although more and more polyacid antitumor drugs have been reported, the potential of polyacids for CDT still needs to be developed, and the technology for constructing polyacids for efficient CDT needs to be developed.

[0004] Compared with various ingeniously designed nanomaterials, polyoxometalates have many unique advantages in CDT: 1) Most of the traditional CDT materials are simple in composition and relatively low in catalytic efficiency. The multi-component and high atomic loading rate of polyoxometalates are conducive to improving the catalytic efficiency. 2) In Fenton / Fenton-like reaction, transition metal ions are indispensable active centers. In contrast, nanoscale polyoxometalates are more likely to bypass the cell barrier and accumulate at the targeted site, thus achieving the desired catalytic effect in the complex physiological microenvironment. 3) The poor dispersibility, limited cell permeability and difficult excretion of traditional CDT materials greatly hinder their clinical application, while the synthesis of polyoxometalates with good dispersibility and biodegradability for CDT will effectively solve this problem. 4) Polyoxometalates have a clear composition and precise atomic structure, and the mechanism of CDT is clear, which is the basis for regulating the structure of polyoxometalate materials and improving the efficacy of CDT. Therefore, designing and synthesizing multi-component polyoxometalate materials with good physiological stability, biodegradability, low toxicity and higher efficacy for CDT is both challenging and of great practical significance. SUMMARY

[0005] To solve the above problems, the application provides preparation and application of a kind of antimony tungstate material with catalytic Fenton-like reaction activity.

[0006] The application adopts the following technical solutions:

[0007] The antimony tungstate material has a molecular formula of H 11 [Ln2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O, which is abbreviated as 1-Ln, wherein Ln=Dy, Ho, Er, Tm, Y, Yb or Lu; DMF=N or N-dimethylformamide; the crystal structure of the antimony tungstate material is a capsule-like isolated cluster structure with a height of 1.9 nm, which is formed by two three-defect {B-alpha-SbW9O 33} units sandwiching a four-nuclear heterometallic cluster {Sb2Ln2O 10 (DMF)2} and a {W7O 29 (OH)} cluster unit, and has good water solubility and stability under physiological conditions.

[0008] Preferably, the crystal structure of the antimony tungstate material belongs to the orthorhombic system, the space group is Pnma, and the space group number is 62.

[0009] Preferably, the unit cell parameters of the antimony tungstate material are: α=β=γ=90°.

[0010] A preparation method of an antimony tungstate material with catalytic Fenton-like reaction activity, comprising the following steps:

[0011] S1, synthesis of a precursor of a trivacant antimony tungstate Na9[B-alpha-SbW9O 33 ]·19.5H2O: S11, preparing a sodium tungstate aqueous solution with a concentration of 1.5-2.0 mol / L and a temperature of 80℃; S12, preparing a concentrated hydrochloric acid solution of antimony, wherein the raw material of antimony is antimony trioxide, and the molar ratio of antimony trioxide to hydrochloric acid is 1:18; S13, adding the concentrated hydrochloric acid solution of antimony dropwise into the sodium tungstate aqueous solution, and refluxing at 80-110℃ for 1-2 hours, and then concentrating the reaction solution to 2 / 3 of the volume, and cooling to room temperature to obtain white crystals, and then washing the crystals with ethanol, and naturally drying to obtain white granular crystals, namely Na9[B-alpha-SbW9O 33 ]·19.5H2O;

[0012] S2, sequentially adding Na9[B-alpha-SbW9O 33 ]·19.5H2O, boric acid and a rare earth salt into a 25 mL polytetrafluoroethylene reactor, and then adding 4-6 mL of deionized water and 2-4 mL of DMF, and then stirring for ten minutes, and then adding 100-300 μL of concentrated hydrochloric acid and 100-300 μL of formic acid dropwise, and then continuing to stir at room temperature for 0.5-3 hours to uniformly mix the raw materials; placing the polytetrafluoroethylene reactor in a constant temperature oven to perform a hydrothermal reaction; after the reaction is cooled to room temperature, the crystals are sucked out, and then vacuum dried to obtain 0.8-2.5 mm yellow petal-shaped crystals, which are the antimony tungstate material with catalytic Fenton-like reaction activity; wherein the molar ratio of Na9[B-alpha-SbW9O 33 ]·19.5H2O, boric acid and the rare earth salt is 2:10:3; the rare earth salt is a rare earth nitrate hexahydrate; the hydrothermal reaction temperature is 80-120℃; and the hydrothermal reaction time is 1-6 days.

[0013] The application of the antimony tungstate material with catalytic Fenton-like reaction activity as an antitumor drug for killing cancer cells by catalyzing the decomposition and consumption of glutathione by H2O2 through a Fenton-like reaction, applied in the field of biological medicine, has high cytotoxicity and selectivity to a variety of cancer cells, can significantly inhibit the growth of tumors in vivo and has little toxic and side effects on normal cells and organs.

[0014] Compared with the background art, the present application has the following advantages:

[0015] 1. The antimony tungstate material (1-Ln) with Fenton-like catalytic activity prepared by this invention has good solubility and stability under physiological conditions, providing an important guarantee for the exploration of nanoscale antitumor drugs.

[0016] 2. The antimony tungstate material (1-Ln) with Fenton-like reaction activity prepared in this invention can generate a large amount of ·OH to kill cancer cells by catalyzing the decomposition of H2O2 and consuming glutathione through Fenton-like reaction. It has high cytotoxicity and selectivity for a variety of cancer cells, can significantly inhibit the growth of tumors in vivo, and has little toxic side effects on normal cells and organs, thus having high safety.

[0017] 3. This invention employs a simple solvothermal treatment process to synthesize antimony tungstate material with Fenton-like catalytic activity in a one-pot method. The synthesis process is simple, with good crystallinity and high yield. This antimony tungstate material with Fenton-like catalytic activity can be used as an antitumor chemodynamic therapy drug in the biomedical field. Attached Figure Description

[0018] Figure 1 A physical image of the 1-Dy antimony tungstate with Fenton-like catalytic activity prepared in this invention;

[0019] Figure 2 The crystal structure diagram of 1-Dy antimonytungstate with Fenton-like catalytic activity prepared in this invention is shown.

[0020] Figure 3 Powder diffraction pattern of 1-Dy antimonytungstate, which has Fenton-like catalytic activity, prepared according to the present invention;

[0021] Figure 4 Electrospray ionization mass spectrum (ESI-MS) of 1-Dy antimony tungstate with Fenton-like catalytic activity prepared in this invention;

[0022] Figure 5 Matching diagram of experimental signal peaks and simulated peaks in the electrospray ionization mass spectrum of 1-Dy antimony tungstate with Fenton-like catalytic activity prepared in this invention;

[0023] Figure 6 High-angle annular dark-field scanning transmission electron microscope (HADDF-STEM) image of antistilbetic acid 1-Dy, which has catalytic Fenton-like reaction activity prepared in this invention, in aqueous solution.

[0024] Figure 7 Hydration particle size and zeta potential of 1-Dy antistilbital acid with Fenton-like catalytic activity prepared in this invention in PBS / water;

[0025] Figure 8 Fenton-like catalytic activity of 1-Dy prepared by the present application and GSH consumption graph;

[0026] Figure 9 Anti-tumor effect of 1-Dy prepared by the present application on B16 cells graph;

[0027] Figure 10 Anti-tumor effect of 1-Dy prepared by the present application in vivo graph;

[0028] Figure 11 Safety evaluation of 1-Dy prepared by the present application graph. DETAILED DESCRIPTION

[0029] In order to make the purpose, technical solutions and advantages of the present application more clear, the present application is further described in detail below in combination with the drawings and examples. It should be understood that the specific examples described herein are only used to explain the present application, and are not used to limit the present application.

[0030] Example 1: Preparation of trivacant antimony tungstate precursor Na9[B-α-SbW9O 33 ]·19.5H2O

[0031] Weigh 40g of sodium tungstate dihydrate into 80mL of deionized water with a temperature of 80℃ to obtain a sodium tungstate solution; then weigh 1.96g of antimony trioxide into 10mL of concentrated hydrochloric acid to obtain a mixed solution; add the mixed solution dropwise into the sodium tungstate solution and reflux at 95℃ for 1 hour, then concentrate the reaction liquid to 2 / 3 of the volume, cool to room temperature to obtain white crystals, filter and wash with ethanol, and naturally dry to obtain white granular crystals, that is, Na9[B-α-SbW9O 33 ]·19.5H2O.

[0032] Example 2: Preparation of compound H 11 [Dy2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O:

[0033] Weigh Na9[B-α-SbW9O 33]·19.5H2O (0.167 mmol, 0.480 g), Dy(NO3)3-6H2O (0.219 mmol, 0.100 g) and H3BO3 (0.566 mmol, 0.035 g) were added into a 20 mL capacity glass bottle, stirred for 10 minutes after adding 5 mL deionized water and 3 mL DMF, 200 μL of HCl and 200 μL of HCOOH were added dropwise, and the raw material was mixed uniformly at room temperature for 1 hour. The glass bottle was placed in a constant temperature oven for solvothermal reaction, the temperature of the solvothermal reaction was 100°C, and the time of the solvothermal reaction was 3 days. After the reaction was taken out, it was naturally cooled to room temperature in the room, the crystals were sucked out, and after vacuum drying, 0.8-2.5 mm yellow transparent petal-shaped crystals were obtained (see Figure 1 ), which is an antimony tungstate material 1-Dy with catalytic Fenton-like reaction activity, and the cell parameters are: α = β = γ = 90°.

[0034] Example 3: Compound H 11 [Ho2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O:

[0035] Na9[B-α-SbW9O 33 ]·19.5H2O (0.167 mmol, 0.481 g), Ho(NO3)3-6H2O (0.230 mmol, 0.106 g) and H3BO3 (0.582 mmol, 0.036 g) were weighed in turn and added into a 20 mL capacity glass bottle, stirred for 10 minutes after adding 5 mL deionized water and 3 mL DMF, 200 μL of HCl and 200 μL of HCOOH were added dropwise, and the raw material was mixed uniformly at room temperature for 1 hour. The glass bottle was placed in a constant temperature oven for solvothermal reaction, the temperature of the solvothermal reaction was 100°C, and the time of the solvothermal reaction was 3 days. After the reaction was taken out, it was naturally cooled to room temperature in the room, the crystals were sucked out, and after vacuum drying, 0.8-2.5 mm yellow transparent petal-shaped crystals were obtained, which is an antimony tungstate material 1-Ho with catalytic Fenton-like reaction activity, and the cell parameters are: α = β = γ = 90°.

[0036] Example 4: Compound H 11 [Er2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O:

[0037] Na9[B-a-SbW9O 33 ]·19.5H2O (0.168 mmol, 0.485 g), Er(NO3)3·6H2O (0.227 mmol, 0.105 g) and H3BO3(0.549 mmol, 0.034 g) were added into a 20 mL capacity glass bottle, stirred for 10 minutes after adding 5 mL deionized water and 3 mL DMF, 200 μL of HCl and 200 μL of HCOOH were added dropwise, and the raw material was mixed uniformly at room temperature for 1 hour. The glass bottle was placed in a constant temperature oven for solvothermal reaction, the solvothermal reaction temperature was 100°C, and the solvothermal reaction time was 3 days. After the reaction was taken out, it was naturally cooled to room temperature in the room, the crystals were sucked out, and after vacuum drying, 0.8-2.5 mm yellow transparent petal-shaped crystals were obtained, which were antimony tungstate materials 1-Er with catalytic Fenton-like reaction activity, and the cell parameters were: α = β = γ = 90°.

[0038] Example 5: Compound H 11 [Tm2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O:

[0039] Na9[B-a-SbW9O 33 ]·19.5H2O (0.168 mmol, 0.485 g), Tm(NO3)3·6H2O (0.220 mmol, 0.102 g) and H3BO3(0.533 mmol, 0.033 g) were added into a 20 mL capacity glass bottle, stirred for 10 minutes after adding 5 mL deionized water and 3 mL DMF, 200 μL of HCl and 200 μL of HCOOH were added dropwise, and the raw material was mixed uniformly at room temperature for 1 hour. The glass bottle was placed in a constant temperature oven for solvothermal reaction, the solvothermal reaction temperature was 100°C, and the solvothermal reaction time was 3 days. After the reaction was taken out, it was naturally cooled to room temperature in the room, the crystals were sucked out, and after vacuum drying, 0.8-2.5 mm yellow transparent petal-shaped crystals were obtained, which were antimony tungstate materials 1-Tm with catalytic Fenton-like reaction activity, and the cell parameters were: α = β = γ = 90°.

[0040] Example 6: Compound H 11 [Yb2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O:

[0041] Na9[B-a-SbW9O 33 ]·19.5H2O (0.168 mmol, 0.485 g), Yb(N03)3-6H2O (0.227 mmol, 0.106 g) and H3B03(0.582 mmol, 0.036 g) were added into a 20 mL capacity glass bottle, stirred for 10 minutes after adding 5 mL deionized water and 3 mL DMF, 200 μΐ^of HC1 and 200 μΐ^of HC00H were added dropwise, and the raw material was mixed uniformly at room temperature for 1 hour. The glass bottle was placed in a constant temperature oven for solvothermal reaction, the solvothermal reaction temperature was 100°C, and the solvothermal reaction time was 3 days. After the reaction was taken out, it was naturally cooled to room temperature in the room, the crystal was sucked out, and after vacuum drying, 0.8-2.5 mm yellow transparent petal-shaped crystals were obtained, which were antimony tungstate materials 1-Yb with catalytic Fenton-like reaction activity, and the cell parameters were: α = β = γ = 90°.

[0042] Example 7: Compound H 11 [Lu2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]·xH2O:

[0043] Na9[B-a-SbW9O 33 ]·19.5H2O (0.168 mmol, 0.485 g), Lu(N03)3-6H2O (0.221 mmol, 0.102 g) and H3B03(0.550 mmol, 0.034 g) were added into a 20 mL capacity glass bottle, stirred for 10 minutes after adding 5 mL deionized water and 3 mL DMF, 200 μΐ^of HC1 and 200 μΐ^of HC00H were added dropwise, and the raw material was mixed uniformly at room temperature for 1 hour. The glass bottle was placed in a constant temperature oven for solvothermal reaction, the solvothermal reaction temperature was 100°C, and the solvothermal reaction time was 3 days. After the reaction was taken out, it was naturally cooled to room temperature in the room, the crystal was sucked out, and after vacuum drying, 0.8-2.5 mm yellow transparent petal-shaped crystals were obtained, which were antimony tungstate materials 1-Lu with catalytic Fenton-like reaction activity, and the cell parameters were: α = β = γ = 90°.

[0044] Example 8: Compound H 11 [Y2Sb2W7O 23 (OH)(DMF)2(SbW9O33 )2]·xH2O:

[0045] Na9[B-α-SbW9O 33 ]·19.5H2O (0.168 mmol, 0.485 g), Y(NO3)3·6H2O (0.274 mmol, 0.105 g) and H3BO3 (0.566 mmol, 0.035 g) were weighed into a 20 mL capacity glass bottle, stirred for 10 minutes after adding 5 mL of deionized water and 3 mL of DMF, 200 μL of HCl and 200 μL of HCOOH were added dropwise, and the raw material was stirred at room temperature for 1 hour to make the mixture uniform. The glass bottle was placed in a constant temperature oven for solvothermal reaction, the solvothermal reaction temperature was 100°C, and the solvothermal reaction time was 3 days. After the reaction was taken out, it was naturally cooled to room temperature in the room, and the crystal was sucked out, vacuum dried to obtain 0.8-2.5 mm yellow transparent petal-shaped crystals, which were the antimony tungstate material 1-Y with catalytic Fenton-like reaction activity, and the cell parameters were: α = β = γ = 90°.

[0046] The compound in the above example belongs to the same compound as 1-Dy of Example 2. H3BO3 in the example acts as a mineralizer in the reaction, which can promote crystallization and help improve the crystal yield. The compound can still be obtained without adding H3BO3, but the yield is lower.

[0047] The series of antimony tungstate crystals obtained in Examples 2-8 belong to the same structure. Taking the 1-Dy antimony tungstate crystal prepared in Example 2 as an example, its basic material properties are as follows:

[0048] Referring to Figures 1-11 :

[0049] Figure 1 is the crystal physical map of the antimony tungstate 1-Dy with catalytic Fenton-like reaction activity prepared by the present application;

[0050] Figure 2 is the crystal structure diagram of the antimony tungstate 1-Dy with catalytic Fenton-like reaction activity prepared by the present application; wherein a) the molecular structure of the compound 1-Dy; b) the {B-α-SbW9O 33} unit; c) the {W7} unit; d) the Sb-Ln heterometallic cluster {Sb2Dy2}; e) the coordination mode of the Dy ion in 1-Dy; f) the simplified diagram of the {Sb2Dy2} atom and the W atom;

[0051] Figure 3 is the powder diffraction diagram of the antimony tungstate 1-Dy with catalytic Fenton-like reaction activity prepared by the present application;

[0052] Figure 4 Electrospray ionization mass spectrum of the antimony tungstate 1-Dy prepared in the application with catalytic Fenton-like reaction activity;

[0053] Figure 5 Matching diagram of experimental signal peaks and simulated peaks of the electrospray ionization mass spectrum of the antimony tungstate 1-Dy prepared in the application with catalytic Fenton-like reaction activity;

[0054] Figure 6 High-angle annular dark field scanning transmission electron microscopy (HADDF-STEM) diagram of the antimony tungstate 1-Dy prepared in the application with catalytic Fenton-like reaction activity in an aqueous solution; wherein, a) is the HADDF-STEM diagram at a scale of 50 nm; b) is the HADDF-STEM diagram at a scale of 10 nm;

[0055] Figure 7 Hydrated particle size and Zeta potential diagram of the antimony tungstate 1-Dy prepared in the application with catalytic Fenton-like reaction activity in PBS / water; wherein, a) is the hydrated particle size distribution diagram of the antimony tungstate 1-Dy prepared in the application with catalytic Fenton-like reaction activity in PBS; b) is the Zeta potential diagram of the antimony tungstate 1-Dy prepared in the application with catalytic Fenton-like reaction activity in an aqueous solution;

[0056] Figure 8 Fenton-like catalytic activity and GSH consumption diagram of 1-Dy prepared in the application; wherein, a) is the ultraviolet light absorption spectrum of ·OH determined using MB / TMB; b) is the visible light absorption spectrum of ·OH determined using MB / TMB; c) is the production diagram of ·OH by ESR spectrum; d) is the determination of the consumption of glutathione after treatment with different concentrations of 1-Dy; e) is the confocal microscope image of B16 cells using DCFH-DA as a detection probe; f) is the diagram of flow cytometry quantitative analysis of the production of intracellular reactive oxygen species;

[0057] Figure 9 Antitumor effect diagram of 1-Dy prepared in the application on B16 cells; wherein, a) is the CLSM image of B16 cells stained with Calcein-AM (live cells) and PI (dead cells) after incubation with 1-Dy; scale bar: 100 μm; b) is the confocal microscope and c) is the flow cytometry to study the effect of 1-Dy on MMP; d) is the representative flow cytometry diagram of control and cells treated with 1-Dy stained with AnnexinV / PI; e) is the statistical analysis of the percentage of early and late apoptosis caused by 1-Dy; f) is the content of MDA in B16 cells after treatment with different doses of 1-Dy;

[0058] Figure 10 Figure 1-Dy in vivo anti-tumor effect diagram prepared by the present application; wherein a) treatment scheme diagram of B16 tumor model; b) tumor growth curve of different treatment groups; c) representative tumor site H&E staining diagram; d) ex vivo tumor photo at the end of treatment; e) tumor growth curve of different treatment groups; f) tumor weight comparison of different treatment groups;

[0059] Figure 11 Figure 1-Dy safety evaluation diagram prepared by the present application; wherein a) hemolysis rate of red blood cell samples treated with different concentrations of 1-Dy; b) body weight growth curve of B16 tumor mice; c) H&E staining of main organs (heart, liver, spleen, lung, kidney) after different treatments.

[0060] (1) Crystal structure determination. Single crystals of appropriate size, regular shape and transparency were selected under a microscope, and the crystal structure was determined by Bruker APEX II CCD diffractometer at 175(2) K, using Mo-Ka ray monochromatized by graphite monochromator as incident light source to collect crystal diffraction data. Shelextl-2018 program was used in structure analysis to analyze and refine the crystal structure by direct method, and the non-hydrogen atoms and their anisotropic treatment parameters were corrected by full matrix least squares method, and all hydrogen atoms were obtained by theoretical hydrogenation. The obtained crystal structure is shown in Figure 2 , and part of the crystallographic data and refinement parameters are shown in Table 1.

[0061] Table 1: Crystal parameter table of compound

[0062]

[0063] (2) Phase characterization. An appropriate amount of the above-mentioned catalytically active antimony tungstate 1-Dy crystal with Fenton reaction was taken, which was ground into powder, and the powder diffraction pattern measured at room temperature (see Figure 3 ) was compared with the diffraction peak simulated according to the single crystal diffraction data. It can be seen that the experimental results are in good agreement with the fitting results of Mercury software, which indicates that the compound is a pure phase; wherein the anisotropy of the crystal causes some differences in peak intensity of the diffraction peaks.

[0064] (3) Dispersion / stability characterization. The stability of compound 1-Dy in aqueous solution was studied by electrospray ionization mass spectrometry (ESI-MS), as shown in Figure 4 and Figure 5 , four groups with different negative charges (6 - , 5 - , 4 - , 3 -) with the theoretical m / z value of the corresponding polyanion cluster (see Table 2). In addition, high-angle annular dark-field scanning transmission electron microscopy (HADDF-STEM) images showed that 1-Dy could be uniformly dispersed in aqueous solution with an average diameter of about 2.0 nm, which was close to the size determined by SCXRD analysis (see Figure 6 ). DLS tests performed in PBS at pH = 7.4 showed that 1-Dy had good monodispersity under physiological conditions, and a negative Zeta potential of -5.18 mV was observed, which corresponded to the negatively charged surface of 1-Dy (see Figure 7 ). Therefore, the solubility and excellent stability of 1-Dy provided a unique opportunity for systematic study of the anti-tumor efficacy of CDT.

[0065] Table 2: Mass spectrometry peak position fitting and related molecular formula of compound 1-Dy at different valence states

[0066]

[0067] The series of antimony tungstate crystals obtained in Examples 2-8 all had catalytic Fenton-like reaction activity. Taking the 1-Dy antimony tungstate crystal prepared in Example 2 as an example, its catalytic Fenton-like reaction catalytic activity and anti-tumor activity were as follows:

[0068] (1) Fenton-like reaction catalytic activity of 1-Dy. The methylene blue (MB) and tetramethyl benzidine (TMB) probes were used to determine the ·OH produced by 1-Dy in solution, MB can be oxidatively degraded by ·OH produced by Fenton-like reaction to form colorless products, and TMB solution can change from colorless to blue. The results showed that 1-Dy could change the MB solution from blue to colorless, and the absorbance at 664 nm wavelength decreased significantly, and with the increase of the concentration of 1-Dy, the degradation of MB gradually increased (see Figure 8 a); at the same time, after 1-Dy reacted with H2O2 and glutathione (GSH) for 10 minutes, the TMB solution changed from colorless to blue and an obvious absorption peak appeared at about 650 nm, which indicated that 1-Dy could effectively catalyze H2O2 to generate ·OH and had Fenton-like reaction catalytic activity (see Figure 8 b). The generation of ·OH was verified by electron spin resonance (ESR) spectrum using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a trapping agent, as shown in Figure 8c) shows that 1-Dy treated with 100 mM H2O2 presents typical ·OH characteristic signal peaks of 1 :2:2:1. In addition, the ROS-based therapy can be effectively improved by consuming GSH, according to which the consumption of GSH was determined by using 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), the principle of which is that GSH reacts with DTNB to generate yellow product thionitrobenzoic acid (TNB), which has a maximum absorption wavelength of 412 nm. The experimental results show that as the concentration of 1-Dy increases, the color of the solution gradually fades and the absorbance also decreases (see Figure 8 d), proving that 1-Dy can consume GSH, thereby weakening the antioxidant capacity of cancer cells and further enhancing the catalytic activity of Fenton-like reaction. Therefore, 1-Dy can be used as an effective CDT anti-tumor drug.

[0069] Subsequently, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) was used as a fluorescent probe to detect the production of intracellular ROS. Confocal laser scanning microscopy (CLSM) images show that, compared with the control group, when treated with 1-Dy and H2O2, B16 cells present strong green fluorescent signals (see Figure 8 e). In addition, the addition of GSH can promote the Fenton-like reaction, thereby enhancing the green fluorescent intensity. Further quantitative detection of intracellular reactive oxygen species levels was carried out by flow cytometry. As shown in Figure 8 f, the addition of H2O2 and GSH significantly enhances the green fluorescence, which is more than 7 times higher than that of the control group. These results are consistent with the observation of CLSM, further indicating that 1-Dy can effectively produce ROS in cancer cells through Fenton-like reaction.

[0070] (2) Anti-tumor activity of 1-Dy. The in vitro cytotoxicity of 1-Dy on normal cells and cancer cell lines was evaluated by MTT method. As shown in Table 3, 1-Dy showed obvious proliferation inhibition activity on 4T1, B16, A549, MD-MB-231 and Hela cancer cells. Specifically, 1-Dy B16 mouse melanoma cancer cells exhibited higher cytotoxicity, with an IC 50 value of 4.75 mM after 72 hours of treatment, and weaker cytotoxicity on normal mouse fibroblasts L929. The in vitro anti-tumor activity of 1-Dy was further studied by Calcein-AM (live cells) / propidium iodide (PI, dead cells) cell staining method, and when the concentration of 1-Dy increased from 5 mM to 50 mM, the CLSM images showed that the green fluorescence of Calcein-AM gradually disappeared, while the red fluorescence of PI gradually increased (see Figure 9 a), proving that 1-Dy has a concentration-dependent anti-cancer effect, which is consistent with the results of MTT experiment.

[0071] Table 3: Cytotoxicity of compound 1-Dy on various cell lines

[0072]

[0073]

[0074] To verify the effect of 1-Dy on mitochondria, Rhodamine 123 (Rh123) staining was used to evaluate the dynamic changes of mitochondrial membrane potential (MMP) of B16 cells under different doses of 1-Dy. CLSM images showed that the green fluorescence signal gradually increased with the increase of 1-Dy concentration, and the Rh123 fluorescence quantitatively analyzed by flow cytometry further confirmed the changes of MMP in B16 cells (see Figure 9 b-c). The above findings indicate that 1-Dy can cause MMP disorder, which in turn triggers B16 cell apoptosis. To clarify the ability of 1-Dy to induce cell apoptosis, Annexin V-FITC / PI staining was performed, and the cell apoptosis was determined by flow cytometry analysis. After 1-Dy treatment, a significant increase in cell apoptosis was observed (see Figure 9 d-e). The results show that 1-Dy can induce B16 cell apoptosis, and the cell apoptosis intensifies with the increase of concentration. Lipid peroxidation (LPO) is one of the most destructive processes in CDT. To investigate whether 1-Dy can induce lipid peroxidation, the content of malondialdehyde (MDA) in cells was further measured. MDA is one of the main products of LPO, and the accumulation of MDA can cause damage to cell membranes and organelles, which is often used to reflect the degree of membrane lipid peroxidation. As shown in Figure 9 f, the accumulation of MDA increases with the increase of the dose of 1-Dy, which indicates that 1-Dy can further induce lipid peroxidation of cell membranes, leading to cell damage. This result further proves that 1-Dy can promote LPO as a CDT agent to improve the chemical kinetic efficacy.

[0075] Finally, the in vivo safety of 1-Dy was verified by hemolysis test. The hemolysis rate of red blood cells co-cultured with different doses of 1-Dy was less than 5%, and no obvious hemolysis phenomenon was observed (see Figure 11 a), which strongly proves that 1-Dy has excellent blood compatibility and does not cause damage to the cell membrane of red blood cells. Therefore, further study was conducted on the potential anti-tumor efficacy of 1-Dy in B16 tumor model (see Figure 10 a). When the tumor volume reached about 100 mm 3 , the tumor mice were randomly divided into 3 groups (five in each group), including PBS, low dose (35 μg / kg) and high dose (70 μg / kg). The mice were intravenously injected with PBS or 1-Dy, once every 3 days, for a total of 7 cycles, and the tumor volume and body weight at each drug administration interval were recorded. As shown in Figure 10b,d-f, compared with the control group, the tumor volume and weight of the treatment group was significantly reduced. In particular, the tumor volume of the high dose 1-Dy group was reduced by nearly 5 times compared with the control group, indicating that 1-Dy has significant anti-tumor activity. In addition, no weight loss or abnormal behavior was observed in all groups (see Figure 11 b). H&E staining showed that compared with the control group, the nuclei and cytoplasm of tumor cells were significantly damaged when treated with 1-Dy drugs (see Figure 10 c), no obvious side effects such as obvious tissue damage and inflammatory reaction of normal tissues were found. In addition, 1-Dy did not cause obvious damage to other organs (heart, liver, spleen, lung, kidney) (see Figure 11 c), again confirming that 1-Dy has excellent anti-tumor effect in vivo and can be used as a safe and efficient CDT cancer treatment drug.

[0076] The above description is only a preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto, any person skilled in the art can easily think of changes or replacements within the technical range disclosed by the present application, which should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A class of antimony tungstate materials exhibiting Fenton-like catalytic activity, characterized in that: The molecular formula of the antimony tungstate material is H. 11 [Ln2Sb2W7O 23 (OH)(DMF)2(SbW9O 33 )2]· x H2O, wherein Ln = Dy, Ho, Er, Tm, Y, Yb or Lu; DMF = N,N-dimethylformamide; the crystal structure of the antimony tungstate material consists of two trivacurized { B - α -SbW9O 33 The units share a common core of a tetra-core heterometallic cluster {Sb₂Ln₂O}. 10 (DMF)2} and a {W7O 29 The (OH)} cluster units form a capsule-shaped isolated cluster structure with a height of 1.9 nm.

2. The antimony tungstate material with Fenton-like catalytic activity as described in claim 1, characterized in that: The crystal structure of the antimony tungstic acid material belongs to the orthorhombic crystal system, with space group [missing information]. Pnma The corresponding spatial group number is 62.

3. The antimony tungstate material with Fenton-like catalytic activity as described in claim 2, characterized in that: The unit cell parameters of the antimony tungstate material are: a = 41.1247 ~ 41.9863(12) (Å), b = 21.1803 ~ 21.7581(6)(Å), c = 13.1243 ~ 13.8453(4) (Å), α = β = γ = 90°.

4. A method for preparing an antimony tungstate material with Fenton-like catalytic activity as described in any one of claims 1-3, characterized in that, Includes the following steps: S1, Tri-vacant antimony tungstate precursor Na9[ B - α -SbW9O 33 Synthesis of 19.5H2O: S11, Prepare an aqueous solution of sodium tungstate at 80℃ with a concentration of 1.5-2.0 mol / L; S12, Prepare a concentrated hydrochloric acid solution of antimony, wherein the antimony raw material is antimony trioxide, and the molar ratio of antimony trioxide to hydrochloric acid is 1:18; S13, Add the concentrated hydrochloric acid solution of antimony dropwise to the aqueous solution of sodium tungstate, and reflux at 80-110℃ for 1-2 hours, then concentrate the reaction solution to 2 / 3 volume, cool to room temperature to obtain white crystals, filter, wash with ethanol, and air dry to obtain white granular crystals, i.e., Na9[ B - α -SbW9O 33 19.5H2O; S2. Sequentially weigh the Na9[ obtained in step S1] B-α -SbW9O 33 19.5 H₂O, boric acid, and rare earth salts were added to a 25 mL polytetrafluoroethylene (PTFE) reactor. Then, 4-6 mL of deionized water and 2-4 mL of DMF were added. After stirring for ten minutes, 100-300 µL of concentrated hydrochloric acid and 100-300 µL of formic acid were added dropwise. Stirring continued at room temperature for 0.5-3 hours to ensure uniform mixing of the raw materials. The PTFE reactor was placed in a constant temperature oven for hydrothermal reaction. After the reaction cooled to room temperature, the crystals were extracted and vacuum dried to obtain 0.8-2.5 mm yellow petal-shaped crystals, which are the antimony tungstic acid material with Fenton-like catalytic activity. The Na₂O₅[…] B- α -SbW9O 33 The molar ratio of 19.5H2O, boric acid, and rare earth salt is 2:10:3; the rare earth salt is rare earth nitrate hexahydrate; the hydrothermal reaction temperature is 80-120℃; and the hydrothermal reaction time is 1-6 days.

5. An application of the antimony tungstate material with Fenton-like catalytic activity as described in claim 1, characterized in that: The antimony tungstate material, as an antitumor drug, is used to generate a large amount of ·OH to kill cancer cells by catalyzing the decomposition of H2O2 and consuming glutathione through a Fenton-like reaction, and is applied in the biomedical field.

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