CN114394623B

CN114394623B - Antimony tungstate oxysalt with anti-tumor bioactivity and preparation method thereof

Info

Publication number: CN114394623B
Application number: CN202210061287.3A
Authority: CN
Inventors: 李新雄; 肖慧萍; 郝亚帅; 徐芃; 郑寿添
Original assignee: Fuzhou University
Current assignee: Fuzhou University
Priority date: 2022-01-19
Filing date: 2022-01-19
Publication date: 2023-04-14
Anticipated expiration: 2042-01-19
Also published as: CN114394623A

Abstract

The invention discloses antimony tungstate oxysalt with anti-tumor bioactivity, the molecular formula of which is H ₃₀ [Tb ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ (SbW ₈ O ₃₀ )(SbW ₉ O ₃₃ ) ₅ ]·30H ₂ O (1-Tb), the crystal structure is { B-alpha-SbW with five three-vacancy positions ₉ O ₃₃ Building blocks and a four-bit-missing { B-beta-SbW } ₈ O ₃₁ The building blocks jointly package a high-nuclear main group-rare earth dissimilar metal cluster { Ln } ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ The compound is a zero-dimensional nanometer-scale isolated cluster structure, the size is about 1.7 multiplied by 1.8 multiplied by 2.6nm, and the compound has good dissolubility and stability under physiological conditions. The compound has good inhibition effect on proliferation of breast cancer cells (4T 1 cells), has small influence on normal cells and has small toxic and side effects on viscera in organisms.

Description

Antimony tungstate oxysalt with anti-tumor bioactivity and preparation method thereof

Technical Field

The invention relates to the technical field of drug synthesis, in particular to antimony tungstate oxysalt with anti-tumor bioactivity, and a preparation method and application thereof.

Background

Cancer is one of the most malignant diseases worldwide, with high morbidity and mortality. Cancer is the second leading cause of death worldwide, as called by the world health organization (http:// www. Who. Int/cancer/en /), with an estimated 960 million people dying from cancer in 2018. Many people are deprived of cancer every year, and the onset of cancer gradually approaches young people, so that the research and cure of cancer are very important. With the development of interdisciplinary disciplines, the application of inorganic chemistry in medicine has become an emerging research area. Over the past decades, nano-drugs based on organic, inorganic or composite materials have been actively developed for preclinical and clinical cancer treatment. The most prominent class of cytotoxic drugs is Cisplatin (CDDP), which is still one of the most clinically used chemotherapeutic drugs to date. In addition to CDDP, a range of other drugs have shown their anti-cancer potential and even cure cancer in rare cases by temporarily relieving symptoms, prolonging patient life. However, they all suffer from some major drawbacks: for example, because of the lack of selectivity leading to serious side effects, inefficiency for certain cancer types, low bioavailability, etc., the search for and discovery of new benign anticancer drugs remains a great challenge, and there is a great need to find alternative drugs to selectively incapacitate cancer cells without seriously damaging normal cells.

Polyoxometalates (POMs) are short for polyacid, and generally refer to a multi-core metal cluster structure formed by condensation polymerization and dehydration of inorganic oxysalts of high-valence transition metals such as V, nb, ta, mo, W and the like, and the Polyoxometalates have rich structure types, modifiable and adjustable sizes and charges, stronger electron and proton transfer/storage capacity, excellent redox performance and good stability. Research in the past decades has shown that polyacids have potential application prospects in biomedical applications, due to their numerous advantages as inorganic drugs, such as the wide variety of polyacids, structural diversity, ability to recognize and act on biological macromolecules (e.g., DNA and RNA); cheap price, easy synthesis, and simultaneously has antiviral, antitumor, antibacterial activity and the like, and is shown to induce apoptosis and inhibit ATP generation.

Disclosure of Invention

The invention aims to provide antimony tungstate oxysalt with anti-tumor bioactivity, a preparation method and application thereof, which can efficiently inhibit the growth of tumor cells and are safe and mild to normal cells and organs.

In order to achieve the purpose, the invention adopts the following technical scheme:

an antimony tungstate oxide salt with anti-tumor bioactivity, wherein:

the antimony tungstate has a molecular formula of H ₃₀ [Tb ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ (SbW ₈ O ₃₀ )(SbW ₉ O ₃₃ ) ₅ ]·30H ₂ O(1-Tb)。

The antimony tungstate oxide has the structural characteristics that: through five three-bit deletions { B-alpha-SbW ₉ O ₃₃ Building blocks and a four-bit-missing { B-beta-SbW } ₈ O ₃₁ The building blocks jointly package a high-nuclear main group-rare earth dissimilar metal cluster { Ln } ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ The crystal structure is a zero-dimensional isolated cluster structure, and the size is about 1.7 multiplied by 1.8 multiplied by 2.6nm.

Preferably, the antimony tungstate is orthorhombic, with space group Pbca corresponding to space group number 61.

Preferably, the antimony tungstate has unit cell parameters of:

α＝β＝γ＝90°。

the invention also provides a preparation method of the antimony tungstate oxide with the anti-tumor bioactivity, which comprises the following steps:

s1, three-vacancy antimony tungstate precursor Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ And (3) synthesis of O: weighing 40g of sodium tungstate dihydrate, and dissolving the sodium tungstate dihydrate in 80mL of deionized water at 80 ℃ to obtain a sodium tungstate solution; then weighing 1.96g of antimony trioxide to dissolve in 10mL of concentrated hydrochloric acid; dropwise adding the solution into a sodium tungstate solution, and refluxing at 95 ℃ for 1 hour; finally, the reaction solution was concentrated to 2/3 of the volume,cooling to room temperature to obtain white crystals, filtering, washing with ethanol, and naturally drying to obtain about 20g of white granular crystals;

s2, sequentially weighing Na prepared in the step S1 ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ O, boric acid and rare earth nitrate are added into a 25mL polytetrafluoroethylene reaction kettle, then 3mL deionized water and 5mL DMMF are added, 200uL concentrated hydrochloric acid is dropwise added after stirring for ten minutes, and the stirring is continued at normal temperature for 1 hour to uniformly mix the raw materials; placing the polytetrafluoroethylene reaction kettle in a constant-temperature oven for hydrothermal reaction; after the reaction is cooled to room temperature, the crystal is sucked out and dried in vacuum to obtain a light yellow strip crystal with the thickness of 0.5-2.0 mm; wherein Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ The mol ratio of O, boric acid and rare earth nitrate is as follows: 2: 10: 3; the rare earth nitrate is Tb (NO) ₃ ) ₃ ·6H ₂ O; the reaction temperature is 140 ℃; the reaction time was 3 days.

The antimony tungstate with anti-tumor bioactivity is applied to the field of anti-tumor drugs, and the antimony tungstate 1-Tb embedded in the main group-rare earth dissimilar metal cluster with anti-tumor bioactivity has a good inhibition effect on proliferation of breast cancer cells (4T 1 cells), and IC (integrated circuit) thereof ₅₀ The value is 1.086 mu M, the influence on normal cells is small, and the toxic and side effects on organs in organisms are small.

After the technical scheme is adopted, the invention has the following beneficial effects:

1) The antimony tungstate oxysalt prepared by the method has good solubility and stability under physiological conditions, and provides important guarantee for exploring nano-scale antitumor drugs.

2) The antimony tungstate 1-Tb prepared by the invention has good inhibition effect on proliferation of breast cancer cells (4T 1 cells), and IC (integrated circuit) of the antimony tungstate 1-Tb ₅₀ The value is 1.086 mu M, and the antitumor cytotoxicity of the compound is superior to that of most polyacid-based nano-medicaments; the compound has small influence on normal cells, small toxic and side effects on organs in organisms, and high safety.

3) The invention has simple synthesis process, good crystallinity and high yield.

Drawings

FIG. 1 is a crystal morphology of antimony tungstate having anti-tumor bioactivity prepared in example 2;

FIG. 2 is a crystal structure diagram of antimony tungstate with anti-tumor bioactivity, wherein a is a polyhedral-ball stick diagram of antimony tungstate of hexamer in compound, and b is a main group-rare earth dissimilar metal cluster { Tb ] embedded in compound ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ A structure diagram of } a;

FIG. 3 is a powder diffraction pattern of antimony tungstate having anti-tumor bioactivity prepared in example 2;

FIG. 4 is an electrospray ionization mass spectrum (ESI-MS) of antimony tungstate having antitumor biological activity prepared in example 2;

FIG. 5 is an infrared spectrum of antimony tungstate having antitumor bioactivity prepared in example 2;

FIG. 6 shows the antimony tungstate oxysalt and precursor Na with anti-tumor bioactivity prepared in example 2 ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ Cytotoxicity test of O and terbium nitrate on breast cancer cells (4T 1);

FIG. 7 is a cytotoxicity test of antimony tungstate salts with antitumor bioactivity prepared in example 2 on normal endothelial cells (EA.hy926);

FIG. 8 is a graph showing the morphological changes of 4T1 cells treated with different concentrations of 1-Tb of antimony tungstate having antitumor biological activity prepared in example 2 for 24 hours;

FIG. 9 is an annexin V-FITC/PI analysis of 4T1 apoptosis by antimony tungstate oxide with anti-tumor bioactivity prepared in example 2;

FIG. 10 is a graph of the size and weight changes of the tumors in the in vivo experiment in mice with antimony tungstate having antitumor bioactivity prepared in example 2;

FIG. 11 is a comparison of the tumor tissue sections of antimony tungstate having antitumor bioactivity prepared in example 2;

FIG. 12 is a histological section of the heart, liver, spleen, lung and kidney of the mice treated with antimony tungstate having antitumor bioactivity prepared in example 2.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Example 1: precursor Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ Preparation of O

Weighing 40g of sodium tungstate dihydrate, and dissolving the sodium tungstate dihydrate in 80mL of deionized water at 80 ℃ to obtain a sodium tungstate solution; then weighing 1.96g of antimony trioxide and dissolving the antimony trioxide in 10mL of concentrated hydrochloric acid; dropwise adding the solution into a sodium tungstate solution, and refluxing at 95 ℃ for 1 hour; and finally, concentrating the reaction solution to 2/3, cooling to room temperature to obtain white crystals, filtering, washing with ethanol, and naturally drying to obtain about 20g of white granular crystals.

Example 2: compound H ₃₀ [Tb ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ (SbW ₈ O ₃₀ )(SbW ₉ O ₃₃ ) ₅ ]·30H ₂ Preparation of O

Sequentially weighing three-vacancy antimony tungstate precursor Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ O (0.17mmol, 0.480g), boric acid (0.82mmol, 0.0500 g) and terbium nitrate hexahydrate (0.27mmol, 0.120g) are added into a 25mL polytetrafluoroethylene reaction kettle, then 3mL deionized water and 5mL DMMF are added, 200uLHCl is dropwise added after stirring for ten minutes, and the stirring is continued for 1 hour at normal temperature to uniformly mix the raw materials; the inner liner of the reaction kettle is put into a stainless steel reaction kettle and placed in a drying oven at 140 ℃ for reaction for 3 days. Taking out the reaction kettle, placing the reaction kettle indoors, naturally cooling to room temperature, sucking out the crystals, and drying in vacuum to obtain the light yellow strip crystals with the thickness of 0.5-2.0mm (see figure 1).

Example 3: compound H ₃₀ [Ln ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ (SbW ₈ O ₃₀ )(SbW ₉ O ₃₃ ) ₅ ]·30H ₂ Preparation of O (Ln = Gd, eu, dy, ho, er)

Sequentially weighing three-vacancy antimony tungstate precursor Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ O (0.17mmol, 0.480g), boric acid (0.82mmol, 0.050g) and nitrate hexahydrate (0.27 mmol) are added into a 25mL polytetrafluoroethylene reaction kettle, then 3mL deionized water and 5mL DMMF are added, 200uLHCl is dropwise added after stirring for ten minutes, and the stirring is continued for 1 hour at normal temperature to uniformly mix the raw materials; the inner liner of the reaction kettle is put into a stainless steel reaction kettle and placed in a drying oven at 140 ℃ for reaction for 3 days. And taking out the reaction kettle, placing the reaction kettle indoors, naturally cooling to room temperature, sucking out the crystals, and drying in vacuum to obtain strip-shaped crystals.

The nitrate hexahydrate of this example comprises gadolinium nitrate hexahydrate, europium nitrate hexahydrate, dysprosium nitrate hexahydrate, holmium nitrate hexahydrate and erbium nitrate hexahydrate, and the compound in this example is an isomorphic compound with 1-Tb of example 2.

Basic characterization of the antimony tungstic oxide salt compound prepared in example 2:

1) Determination of Crystal Structure

Selecting a single crystal with proper size, regular shape and transparency under a microscope, and monochromating Mo-Kalpha rays at 175 (2) K by a graphite monochromator through a Bruker APEX II CCD diffractometer

As an incident light source to collect crystal diffraction data. In the structure analysis, a Shelextl-2018 program is used for analyzing and refining the crystal structure by a direct method, meanwhile, non-hydrogen atoms and anisotropic treatment parameters thereof are corrected by a full matrix least square method, all hydrogen atoms are obtained by theoretical hydrogenation, and the obtained crystal junctionThe pattern is shown in FIG. 2. Some crystallographic data and refinement parameters are shown in table 1:

table 1: crystal parameter table of compound

(2) Powder diffraction characterization:

a proper amount of the crystal prepared by the method is fully ground into powder, and the comparison between a powder diffraction pattern measured at normal temperature (shown in figure 3) and a diffraction peak simulated according to single crystal diffraction data shows that the experimental measurement result is better matched with the fitting result of Mercury software, so that the compound is proved to be pure phase. Wherein the anisotropy of the crystals causes a difference in the peak intensity of the partial diffraction peaks.

(3) And (3) stability testing:

the stability of compound 1-Tb in aqueous solution was investigated by electrospray ionization mass spectrometry (ESI-MS) and five groups of peaks corresponding to different negative charges (9-, 8-, 7-, 6-, 5-) were observed in the ESI-MS spectrum (see FIG. 4), with five species with larger m/z values detected at m/z 1957.12,2208.75,2530.86,2973.02,3597.63, which are consistent with the simulated m/z values, indicating that the structure has good stability in aqueous solution. In addition, the stability of 1-Tb in water, PBS and cell culture medium was further confirmed by Fourier transform infrared spectroscopy. As shown in fig. 5, no significant change in the characteristic cluster signal was observed in the spectra after 24 hours incubation in the above solutions, indicating that 1-Tb has high stability under physiological conditions.

1) Antitumor activity test procedure:

cell culture: mouse breast cancer (4T 1) cells were purchased from the chinese academy of sciences; 4T1 cells were plated in RPMI-1640 medium containing 10% FBS, and EA.hy926 cells were plated in RPMI-1640 medium containing 10% fetal bovine serum (FBS, gibco) and 1% penicillin-chainIn DMEM medium containing a mycin solution; all cells were assayed at 37 ℃ and 5% ₂ Culturing in a humidifying incubator.

In vitro cytotoxicity assay: 1-Tb and two starting materials (Tb (NO) ₃ ) ₃ ·6H ₂ O、Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ O) cytotoxicity on a panel of tumor cells including 4T1 and ea.hy926 cells was tested by CellKit-8 (CCK 8), while ea.hy926 cells were used as a non-tumor cell control. The cells were cultured at 6X 10 ³ The density of individual cells/well was seeded in 96-well cell culture plates, treated with different concentrations of 1-Tb for 24 hours, and then incubated with 100. Mu.L/well of 10% CCK8 solution. After an additional incubation of 0.5-4 hours at 37 ℃. Absorbance was measured at 450nm using a microplate reader. IC was calculated by probability analysis using GraphPad Prism8 software ₅₀ (half maximal inhibitory concentration) value. Cell viability curves were plotted for 1-Tb treatment compared to the control group. Cell viability was calculated using the following equation: cell viability (%) = OD treatment/OD control × 100%.

Nuclear morphology: 4T1 cells were plated at 5X 10 ⁵ Density of individual cells/well seeded on Beyogold ^TM 35mm glass-based confocal dishes and allowed to grow for 24 hours. Then, the cells were treated with 1-Tb (0, 10, 20. Mu.M, respectively) at 37 ℃ for 24 hours. Subsequently, the cells were washed 1 time with PBS, stained for 15min with Hoechst33342 at room temperature, washed 2 times with PBS, and the nuclear morphology was observed under a fluorescence microscope and photographed at 60-fold magnification.

Flow cytometry analysis of apoptosis: for apoptosis assays, 4T1 cells were treated with 1-Tb at 20, 10, 5, 2.5 and 0 μ M for 24 hours, respectively. Apoptotic cells were determined using Annexin-V-FITC/PI apoptosis detection kit. Fresh cells were collected and resuspended in 500. Mu.L of binding buffer and stained with 5. Mu.L of Annexin-V-FITC and 5. Mu.L of propidium iodide. Finally, BD Accuri is used ^TM C6 The samples were analyzed by Plus flow cytometry.

In vivo experiments: 4T1 cells (1.75X 10) ⁶ ) Subcutaneously to the right back of female Balb/c mice (6-8 weeks) waiting for the tumor to reach 70mm ³ Left and right. The mice were divided into two groups (5 mice per group) for various treatments. Mice of one group were injected subcutaneously with 100. Mu.L of 1Tb (in saline) at a dose of 50mg/kg, once in two days, based on the weight of the mice, for 21 days. Another group of mice was injected subcutaneously with 100. Mu.L of physiological saline as a reference subject. Each mouse was monitored for body weight and tumor size 8 times every two days. Tumor volume calculated as Width ² X length/2. Mice were sacrificed on day 30 from the figure and organs (heart, liver, spleen, lung, kidney) were collected for hematoxylin-eosin (H)&E) And (4) dyeing and analyzing.

(2) Analysis of anti-tumor activity test results:

to test the antitumor activity of 1-Tb on breast cancer (4T 1) cell lines, we assayed the cytotoxicity of cells after 24 hours incubation with different concentrations of 1-Tb. For comparison, we also determined the cytotoxicity of 1-Tb against the normal endothelial cell line ea.hy926 to assess its specificity for tumor cell lines. 1-Tb inhibited the proliferation of all cancer cells in a dose-dependent manner. At high concentrations, the viability of breast cancer cells was inhibited to 9.7%. Corresponding IC of 1-Tb ₅₀ The value (concentration of 50% growth inhibition) was 1.086. Mu.M, indicating that 1-Tb may have a significant inhibitory effect on breast cancer cells. To further understand the anti-tumor mechanism of 1-Tb, the cytotoxicity of the starting material was also tested in 4T1 cells (see fig. 6). Na (Na) ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ O showed moderate cytotoxicity in 4T1 cells with an IC50 value of 22.37. Mu.M, and Tb (NO) ₃ ) ₃ ·6H ₂ O showed no cytotoxicity even at high concentrations (see table 2). The results indicate that the antitumor effect of 1-Tb was Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ O20 fold, further indicating that the cluster structure of 1-Tb also contributes to cytotoxicity. Furthermore, 1-Tb was not toxic to the endothelial cell line EA.hy926 (see FIG. 7), indicating that 1-Tb is more specific for tumor cells than for healthy cells and that 1-Tb is safe for transport in the circulation.

Table 2: results of cytotoxicity test

To reveal the potential mechanism by which compound 1-Tb inhibits tumor cell viability, we studied the morphological changes of 4T1 nuclei after 1-Tb treatment using the nucleic acid stain Hoechst33342 to visualize nuclear debris and chromatin condensation to form apoptosis. For this, 4T1 cells were treated with different concentrations of 1-Tb for 24 hours, then stained with Hoechst33342, and subsequently examined by confocal laser scanning microscopy. The 1-Tb treated cells showed nuclear deformation as represented by nuclear fragmentation and some bright blue fluorescent clumps due to nuclear condensation, indicating that 1-Tb triggered apoptosis, compared to untreated cells (see FIG. 8). This prompted us to perform Annexin V-FITC/PI analysis to quantitatively investigate 1-Tb induced apoptosis and necrosis of tumor cells by flow cytometry analysis. As shown in fig. 9. 1-Tb dose-dependently increased the proportion of early and late apoptotic cells after 24 hours of treatment compared to untreated controls. In addition, as the concentration of the drug increases, the proportion of cells changes from early apoptosis to late apoptosis, with partial cell necrosis. Taken together, the results indicate that 1-Tb inhibits tumor growth by a complex mechanism combining apoptosis and necrosis.

We subsequently further investigated the anti-tumor effect of 1-Tb in vivo using a subcutaneous tumor-transplanted mouse model. Murine mammary carcinoma cells 4T1 were implanted subcutaneously into the right side of female Balb/c mice. The tumor volume reaches 50-200mm ³ Thereafter, the mice were randomly divided into three groups, and administered with physiological saline and 50mg/kg1-Tb every other day, respectively. Tumor volume and body weight were monitored every two days (see figure 10). The results show that the administration of 1-Tb significantly inhibited tumor growth. On day 21, tumor tissue was excised and weighed after mice were anesthetized. The average tumor weight of mice treated with 1-Tb was observed to be 0.952g, while the control group showed an average weight of 1.492g. Furthermore, the non-significant change in body weight (average body weight ranging from 18.43 to 20.62 grams) demonstrates that the side effects of 1-Tb are tolerable (see fig. 10 c). Hematoxylin and eosin (H) of tumor tissue&E) The stained histopathological sections showed the presence of inflammatory lesions and local necrosis in the 1-Tb treated tumor tissue, while a significant amount of tissue damage was present in the tumor tissue of the control group (see fig. 11). Notably, histopathological sections were visualizedLung tissue from untreated tumor-transplanted mice was shown to have significant metastatic cells (see fig. 12). In contrast, relatively clear lung tissue was observed in the 1-Tb treated group, indicating that 1-Tb had a potent anti-metastatic effect. Histopathological analysis also showed that 1-Tb did not cause significant damage to other organs (heart, liver, spleen and kidney) (see FIG. 12).

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims

1. An antimony tungstate oxysalt with anti-tumor bioactivity, which is characterized in that:

the molecular formula of the antimony tungstate oxysalt is H ₃₀ [Tb ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ (SbW ₈ O ₃₀ )(SbW ₉ O ₃₃ ) ₅ ]·30H ₂ O；

The antimony tungstate oxide has the structural characteristics that: through five three-bit deletions { B-alpha-SbW ₉ O ₃₃ Building blocks and a four-bit-missing { B-beta-SbW } ₈ O ₃₁ The building blocks jointly package a high-nuclear main group-rare earth dissimilar metal cluster { Tb } ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ And (4) forming hexameric antimony tungstate oxide with a crystal structure of a zero-dimensional isolated cluster structure and a size of 1.7 × 1.8 × 2.6nm.

2. The antimony tungstate of claim 1, wherein: the antimony tungstate oxysalt belongs to an orthorhombic system, a space group is Pbca, and a corresponding space group number is 61.

3. The antimony tungstate of claim 2, wherein the antimony tungstate has an antitumor biological activity: the unit cell parameters of the antimony tungstate oxysalt are as follows:

α＝β＝γ＝90°。

4. a process for the preparation of antimony tungstate as claimed in any one of claims 1 to 3, wherein the process comprises the following steps:

s1, three-vacancy antimony tungstate precursor Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ And (3) synthesis of O: weighing 40g of sodium tungstate dihydrate, and dissolving the sodium tungstate dihydrate in 80mL of deionized water at 80 ℃ to obtain a sodium tungstate solution; then weighing 1.96g of antimony trioxide and dissolving the antimony trioxide in 10mL of concentrated hydrochloric acid; dropwise adding the solution into a sodium tungstate solution, and refluxing for 1 hour at 95 ℃; finally, concentrating the reaction solution to 2/3 of the volume, cooling to room temperature to obtain white crystals, filtering, washing with ethanol, and naturally drying to obtain 20g of white granular crystals;

s2, sequentially weighing Na prepared in the step S1 ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ Adding O, boric acid and rare earth salt into a 25mL polytetrafluoroethylene reaction kettle, then adding 3mL deionized water and 5mL DMF, stirring for ten minutes, then dropwise adding 200uL concentrated hydrochloric acid, and continuously stirring at normal temperature for 1 hour to uniformly mix the raw materials; placing a polytetrafluoroethylene reaction kettle in a constant-temperature oven to carry out hydrothermal reaction; after the reaction is cooled to room temperature, the crystal is sucked out and dried in vacuum to obtain a light yellow strip crystal with the thickness of 0.5-2.0 mm; wherein Na ₉ [B-α-SbW ₉ O ₃₃ ]·19.5H ₂ The mol ratio of O, boric acid and rare earth salt is as follows: 2: 10: 3; the rare earth salt is terbium nitrate hexahydrate; the hydrothermal reaction temperature is 140 ℃; the hydrothermal reaction time was 3 days.

5. The use of antimony tungstate of claim 1, which has antitumor activity: antimony tungstate H embedded with main group-rare earth dissimilar metal cluster and having anti-tumor bioactivity ₃₀ [Tb ₇ Sb ^Ⅲ ₁₃ Sb ^Ⅴ ₂ W ₃ O ₃₂ (C ₃ NH ₇ O)(H ₂ O) ₆ (SbW ₈ O ₃₀ )(SbW ₉ O ₃₃ ) ₅ ]·30H ₂ O for inhibiting breast cancer 4T1 cell, and IC thereof ₅₀ The value was 1.086. Mu.M.