CN111110637A - Paratungstate nano material and preparation method and application thereof - Google Patents

Abstract

The invention provides an paratungstate nano material, a preparation method and an application thereof, and the paratungstate nano material provided by the invention comprises the following components: an paratungstate and a carrier; wherein the paratungstate is Na₁₀H₂W₁₂O₄₂·26H₂O; experiments show that the sodium stearate is used as the carrier, so that the obtained nanoparticles have higher tumor inhibition activity and obviously reduced toxicity to normal cells compared with the paratungstate; moreover, the method provided by the invention is simple, easy to realize and has good industrial application prospect.

Description

Paratungstate nano material and preparation method and application thereof

Technical Field

The invention relates to the field of medicines, and in particular relates to an paratungstate nano material as well as a preparation method and application thereof.

Background

Polyoxometalates (POMs), also known as polyacids, include heteropolyacids and isopolyacids, and are d⁰The metal-oxygen cluster compound with a space network structure formed by high polymerization of the configured transition metal ions and oxygen has more than thirty years of history of anti-tumor effect research, has the advantages of wider anti-tumor effect spectrum and certain inhibition effect on tumor cells, and certain types of polyacid have more satisfactory anti-tumor effect than the current commercial medicaments in the aspect of tumor inhibition effect^[1，2]. Recent research reports show that although POMs have certain antitumor activity, the existing compounds are still unsatisfactory in the aspects of solubility, drug activity and specificity of intracellular target points^[3，4]。

paratungstate-B is a classical isopoly acid^[5，6，7]Structural formula is [ H ]₂W₁₂O₄₂]^10-Has good anti-HIV activity. In 2016, four standard cell lines of HepG-2 (liver cancer), HeLa (cervical cancer), Skov-3 (ovarian cancer) and SHY5Y (glioma cell) are selected from the group of Zaozhu subjects, and a cell culture and drug screening model is established, so that the synthesized novel paratungstate-B molecule is found to have anti-tumor activity^[8]. However, the activity of the paratungstate as an antitumor drug is still not very high, so that the improvement of the activity of the paratungstate is of great significance.

[1] Wanengbo, Huchang, Schering. polyacid chemistry introduction to Beijing: chemical industry publishers, 1998.

[2]Yamase T，Fujita H，Fukushima K.Medical chemistry ofpolyoxometalates.Part 1.Potent.antitumor activity of polyoxomolybdates onanimal transplantable tumors and human cancer xenograft[J].Inorganica ChimicaActa，1988，151(1)：15-18.

[3]Yanagie H，Ogata A，Mitsui S.et al.Anticancer activity ofpolyoxomolybdate[J].Biomedicine&Pharmacotherapy，2006，60(7)：349-352.

[4]Bijelic A，Aureliano M，Rompel A.Polyoxometalates as potential next-generation metallodrugs in the combat against cancer[J].Angewandte ChemieInternational Edition，2019，58(10)：2980-2999.

[5] Study of bridged compounds based on Keggin polyoxometallate and paratungstate-B [ D ], university of northeast catharanthus, 2009.

[6] Research on functionalized inorganic-organic hybrid compounds based on B-type paratungstates and Anderson-type polyoxometallates [ D ], vinca: northeast university, 2010.

[7]CarlosGimbnez-SaizJ，JoseRam，GalBn-Mascar，SmailTrikiJ，EugenioCoronado.

[(Co(H₂₀)₄)₂(H₂W₁₂O₄₂)]：A Novel Chainlike Heteropolyanion Formed byParadodecatungstate and Co(II)Ions[J]，Inorg.Chem.1995，(34)：524-526.

[8]Zuozhu et al, novel paratungstate-B compound [ Na₂(H₂O)₁₀][Cu₄(H₂O)₁₂(H₂W₁₂O₄₂)]·15H₂O in vitro antitumor Activity study [ J]2016, molecular science bulletin.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide an paratungstate nanomaterial, and a preparation method and an application thereof.

The invention provides a paratungstate nano material, which comprises the following components: an paratungstate and a carrier;

wherein the paratungstate is Na₁₀H₂W₁₂O₄₂·26H₂O; the carrier is sodium stearate.

Preferably, the particle size of the paratungstate nanoparticles is 200-1000 nm.

The invention also provides a preparation method of the paratungstate nano material, which comprises the following steps:

1) mixing Na₁₀H₂W₁₂O₄₂·26H₂Injecting the water solution of O into the sodium stearate solution, and adding a sodium chloride solution to obtain a mixed solution;

2) and regulating the pH value of the obtained mixed solution to 3.5-4.5 by using hydrochloric acid, and carrying out mixing reaction to obtain the paratungstate nano material.

Preferably, the Na is₁₀H₂W₁₂O₄₂·26H₂The concentration of the O aqueous solution is 0.08-0.15 g/mL.

Preferably, the sodium stearate solution is prepared according to the following method:

heating an ethanol solution of stearic acid to 55-85 ℃, and then dripping a sodium hydroxide solution into the solution until the solution is colorless and transparent to obtain a sodium stearate solution.

Preferably, the concentration of the ethanol solution of stearic acid is 0.05-0.1 g/mL.

Preferably, said stearic acid is reacted with said Na₁₀H₂W₁₂O₄₂·26H₂The mass ratio of O is (0.2-0.35) to 1.

Preferably, the sodium chloride is in contact with the Na₁₀H₂W₁₂O₄₂·26H₂The mass ratio of O is (0.08-0.12) to 1.

Preferably, the pH value of the mixed solution in the step 2) is adjusted to 3.8-4.2.

The invention provides an application of the nano-material of tungstate in preparing antitumor drugs.

Compared with the prior art, the invention provides an paratungstate nano material, which comprises the following components in percentage by weight: an paratungstate and a carrier; wherein the paratungstate is Na₁₀H₂W₁₂O₄₂·26H₂O; experiments show that the sodium stearate is used as the carrier, so that the obtained nanoparticles have higher tumor inhibition activity and obviously reduced toxicity to normal cells compared with the paratungstate; moreover, the method provided by the invention is simple, easy to realize and good in performanceAnd (4) industrial application prospect.

Drawings

NaW in FIG. 1₁₂-LEP nanoparticle Scanning Electron Microscopy (SEM) images;

NaW in FIG. 2₁₂-LEP、NaW₁₂And NaW₁₂Infrared spectrum of physical mixture with sodium stearate;

NaW in FIG. 3₁₂-LEP and NaW₁₂An XRD pattern;

NaW in FIG. 4₁₂A standard curve;

NaW in FIG. 5₁₂OD 24h after LEP treatment of HepG2, HeLa and EVC-304 cells;

NaW in FIG. 6₁₂-inhibition rate 24h after LEP treatment of HepG2, HeLa and EVC-304 cells;

FIG. 7 is an inverted microscope NaW₁₂-cell morphology change profile of LEP-treated HepG 2;

FIG. 8 is an inverted microscope NaW₁₂Map of morphological changes of LEP-treated HeLa cells.

Detailed Description

The invention provides an paratungstate nano material, which comprises the following components in part by weight: an paratungstate and a carrier; wherein the paratungstate is Na₁₀H₂W₁₂O₄₂·26H₂O; the carrier is sodium stearate. Preferably, the particle size of the paratungstate nanoparticles is preferably 200-1000nm, and more preferably 300-800 nm.

The invention also provides a preparation method of the paratungstate nano material, which comprises the following steps:

1) mixing Na₁₀H₂W₁₂O₄₂·26H₂Injecting the water solution of O into the sodium stearate solution, and adding a sodium chloride solution to obtain a mixed solution;

2) and regulating the pH value of the obtained mixed solution to 3.5-4.5 by using hydrochloric acid, and carrying out mixing reaction to obtain the paratungstate nano material.

According to the invention, Na is added to the mixture₁₀H₂W₁₂O₄₂·26H₂The aqueous solution of O is poured into the sodium stearate solution and added with chlorideSodium solution to obtain a mixed solution; wherein, the Na₁₀H₂W₁₂O₄₂·26H₂The concentration of the O aqueous solution is preferably 0.08-0.15 g/mL, most preferably 0.10-0.12 g/mL, and more preferably 0.107 g/mL; the sodium chloride is in contact with the Na₁₀H₂W₁₂O₄₂·26H₂The mass ratio of O is (0.08-0.12) to 1; preferably (0.10-0.11) to 1; the method for injecting the sodium stearate solution is not particularly required by the invention, and any injection method known in the art can be adopted, for example, a laboratory can adopt a microporous filter membrane injection needle for injection.

In the invention, the sodium stearate solution is prepared according to the following method:

heating an ethanol solution of stearic acid to 55-85 ℃, preferably 65-75 ℃, and then dripping a sodium hydroxide solution into the solution until the solution is colorless and transparent to obtain a sodium stearate solution; wherein the concentration of the ethanol solution of stearic acid is preferably 0.05-0.1 g/mL, more preferably 0.06-0.09 g/mL, and most preferably 0.07-0.08 g/mL; the concentration of the sodium hydroxide solution is preferably 0.03-0.06 g/mL, more preferably 0.046-0.050 g/mL; the stearic acid and the Na₁₀H₂W₁₂O₄₂·26H₂The mass ratio of O is (0.2-0.35) to 1, preferably (0.25-0.32) to 1, and more preferably (0.28-0.30) to 1.

According to the invention, the pH value of the obtained mixed solution is adjusted to 3.5-4.5 by hydrochloric acid, and the mixed solution is mixed and reacted to obtain the paratungstate nano material, wherein the pH value of the mixed solution is preferably adjusted to 3.8-4.2, and more preferably 4-4.1; the invention has no special requirement on the temperature of the mixing reaction, and the reaction can be carried out at normal temperature; the reaction time is preferably 1.5 to 3 hours, and more preferably 2 to 2.5 hours. After the reaction is finished, the mixed solution is preferably still kept stand, and the obtained precipitate is sequentially washed by ethanol and distilled water and dried to obtain the nano-material of the paratungstate.

The invention also provides an application of the tungstate nanometer material in preparation of antitumor drugs; wherein, the anti-tumor drug is preferably a drug for resisting the proliferation of the HeLa cells of cervical cancer cells or a drug for resisting the proliferation of the HepG2 cells of human liver cancer cells.

The sodium stearate is loaded with Na₁₀H₂W₁₂O₄₂·26H₂The sodium stearate is used as a carrier, so that the obtained nanoparticles have higher tumor inhibition activity and obviously reduced toxicity to normal cells compared with the paratungstate; moreover, the method provided by the invention is simple, easy to realize and has good industrial application prospect.

The following will clearly and completely describe the technical solutions of the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Examples

1 experimental part

1.1 Experimental reagents and instruments

Na₂WO₄·2H₂O, analytically pure, Tianjin, Daloco chemical reagent plant; CH (CH)₃COONa, analytically pure, Renjite Chemicals, Inc., Tianjin; CH (CH)₃(CH₂)₁₆COOH, analytically pure, Renjite Chemicals, Inc., Tianjin; NaCl, analytically pure, Tianjin, northern Tianyi chemical reagent factory; HCl, analytical pure, Yongda chemical reagents, Inc., Tianjin; NaOH, analytical pure, Tianjin, Daloco chemical reagent works.

3- (4, 5-Dimethylthiazol-2) -2, 5-diphenyltetrazolium bromide (MTT) and DMSO were obtained from sigma, USA; fetal bovine serum, RPMI 1640(pH7.0-7.2), trypsin were purchased from Gibco; diabesin (penicillin sodium, streptomycin sulfate) was purchased from west drug company. XTL-2400 microscope, Shanghai Baoto instruments Inc.; an AlpHa CentaurtFT/IR type infrared spectrometer; TU-1901 model ultraviolet spectrometer, Beijing Pujingyo Instrument, Inc.; an E1ementarVario MICRO model element analyzer;brucker focus type X-ray diffractometer; FLB-lB model ultra clean studio, Suzhou Sujing group; american SHELL/JB type CO₂Constant temperature cell culture case.

1.2 Experimental methods

1.2.1 NaW₁₂Synthesis of (2)

1.98g (6.0mmmol) of Na₂WO₄·2H₂O is dissolved in 40ml of buffer solution (preparation: 5.5ml of glacial acetic acid is measured, 13.6g of sodium acetate is weighed, and 100ml of distilled water is added). Heating at 70 deg.C for 45min under stirring, and cooling to room temperature. After several days, washing and drying to obtain white crystal, namely Na₁₀H₂W₁₂O₄₂·26H₂O (abbreviated as NaW)₁₂)。

1.2.2 paratungstate nanomaterial (NaW)₁₂-LEP) Synthesis

0.84g of stearic acid is dissolved in 11ml of absolute ethanol, the mixture is placed in a beaker and heated to 65 ℃ in a magnetic stirrer, and NaOH (0.51 g of NaOH solid is weighed and dissolved in 11ml of distilled water) solution is gradually dripped into the beaker and stirred continuously (the operation step is also under a heating state) until the colorless mixed solution becomes transparent. NaW will be mixed₁₂(3g in 28ml water) was dissolved in preheated distilled water and added to a beaker by infusion (repeated experiments using a microfiltration membrane placed in front of the injection needle) to determine a pH of 7-8. 0.32g of NaCl solid was weighed out and dissolved in 3ml of distilled water, added to a beaker and adjusted to pH 4 with hydrochloric acid to form a white suspension. After reacting for two hours at normal temperature on a magnetic stirrer, the suspension was left to stand for three hours. Filtering the obtained precipitate, washing with ethanol and distilled water, and drying to obtain NaW₁₂-LEP。

2 results and discussion

2.1 NaW₁₂Characterization of the LEP nanoparticles

2.1.1 morphology

Grinding the nanoparticles into fine powder, placing into a beaker, adding ethanol to suspend the nanoparticles in the solution, dispersing the nanoparticles uniformly, and observing the appearance of the polyacid nanoparticles under a Scanning Electron Microscope (SEM), the result is shown in FIG. 1, which is NaW in FIG. 1₁₂-LEP nanoparticle Scanning Electron Microscopy (SEM) images; as can be seen from FIG. 1, NaW was obtained₁₂Under a scanning electron microscope, most of the LEP particles are elliptic, and few of the LEP particles are spherical. The synthesized product is nano-sized, and the particle size distribution of the nano-particles is between 200 and 1000 nm.

2.1.2 Infrared Spectrum

NaW₁₂The IR spectrum of the LEP is shown in FIG. 2, which is NaW in FIG. 2₁₂-LEP、NaW₁₂And NaW₁₂The infrared spectrum of the physical mixture with sodium stearate shows that the infrared spectrum of the nano particles is almost unchanged compared with that of the raw material medicine, which indicates that the polyacid compound in the nano particles keeps the parent structure. Specifically, in the IR spectrum, it was found that the peak intensity was 3422.6cm^-1The characteristic peak in the broad peak is the characteristic peak of water molecule. At 1002.8, 934.7, 719.5 and 688.4cm^-1The characteristic peaks appearing there can be classified as the vibration of the polyanions υ (W ═ Ot), υ (W-O-W) and υ (W-O-W), respectively, which is presumed to indicate NaW₁₂the-LEP has a polyacid specific α -Keggin structure, and an absorption peak is relative to NaW₁₂A blue or red shift occurs, causing a change in the characteristic peak position, NaW₁₂LEP is not purely physical mixing, but forms a drug delivery system. The specific results are analyzed in Table 1.

TABLE 1 NaW₁₂-LEP、NaW₁₂Comparison with the Infrared Spectrum of a physical mixture

2.1.3 XRD

As shown in fig. 3, NaW in fig. 3₁₂-LEP and NaW₁₂An XRD pattern; NaW₁₂Diffraction peaks of LEP with NaW₁₂Similarly, but NaW₁₂The diffraction peak intensity of the LEP is weakened and markedly broadened, NaW at 8 °, 15 °, 42 °₁₂Has a very sharp absorption peak, but NaW₁₂Significant weakening or even complete disappearance of LEPIndicating the presence of NaW in the synthesized product₁₂However, the crystallinity is reduced and the particle size is reduced.

2.1.4 ultraviolet-visible Spectrum

NaW₁₂An absorption peak at 192nm is a characteristic absorption peak of Keggin type polyoxometallate and is attributed to the charge transfer transition from terminal oxygen to tungsten atom Ot-W. Thus, synthesized NaW₁₂LEP UV spectrum, also with an absorption peak at 192nm, indicating the presence of NaW in the synthesized nanoparticles₁₂。

2.2 NaW₁₂Quantitative analysis of LEP polyacid nanoparticles

Linear regression of the absorbance (A, Abs) versus concentration (C, μ g/ml) was performed as shown in FIG. 4, which is NaW in FIG. 4₁₂Standard curve, drawing NaW₁₂Fitting an equation to obtain:

y＝0.0254x+0.2863(R²＝0.999)

NaW measured at a wavelength of 192nm₁₂-absorbance of LEP, a ═ 0.98, drug concentration by comparison to standard curve, i.e. NaW was obtained by substituting absorbance into standard curve₁₂The concentration of LEP was 27.31. mu.g/ml.

The results show NaW₁₂NaW in LEP₁₂The drug content of (1) is 12.41% (g/g).

(content: NaW₁₂NaW in LEP₁₂Quality of/NaW₁₂Quality of LEP)

2.4 NaW₁₂Study of the antitumor Activity of LEP

2.4.1 NaW₁₂Antitumor activity

MTT colorimetric test

Since mitochondria of living cells have the ability to reduce MTT to form purple compounds, the compounds have strong absorption at a wavelength of 570 nm. When the cell death or proliferation function is decreased, the ability to reduce MTT is decreased, and the absorbance at 570nm is decreased. NaW of different concentrations₁₂Has inhibitory effect on ECV-304, HeLa and HepG2 cells, and the survival rate of the cells decreases with the increase of concentration, NaW₁₂IC for ECV-304, HeLa and HepG2 cells₅₀Respectively is 125.4 mu mol.L^-1、160.5μmol·L^-1And 120.3. mu. mol. L^-1。

2.4.2 NaW₁₂-LEP antitumor activity

(1) MTT colorimetric assay compounds absorb strongly at a wavelength of 570nm due to the ability of mitochondria of living cells to reduce MTT to form purple compounds. When the cell death or proliferation function is decreased, the ability to reduce MTT is decreased, and the absorbance at 570nm is decreased. As shown in the table, NaW was added at various concentrations compared to the control₁₂LEP has inhibitory effect on HeLa and HepG2 cells, and the survival rate of the cells decreases with increasing concentration, and has drug dose dependence, IC₅₀Respectively is 48.4 mu mol. L^-1And 3.42. mu. mol. L^-1. With parent polyacid (NaW)₁₂) In contrast, the pharmacological activity of the tumor cells is obviously enhanced, and the specific results are shown in Table 2, and figure 5 and figure 6, wherein figure 5 is NaW₁₂OD 24h after LEP treatment of HepG2, HeLa and EVC-304 cells; NaW in FIG. 6₁₂Inhibition rate after LEP treatment of HepG2, HeLa and EVC-304 cells for 24 h.

TABLE 2 NaW₁₂And NaW₁₂IC of LEP for HeLa and HepG2 cells₅

(2) NaW of different concentrations₁₂Effect of LEP on tumor cell morphology

NaW of different concentrations₁₂The effect of LEP on EVC-304, HeLa and HepG2 cell morphology is shown in the figure. NaW at concentrations of 100nm, 1. mu.M, 10. mu.M, 50. mu.M and 100. mu.M, respectively₁₂After 24h of EVC-304, HeLa and HepG2 cells treated by LEP, the results show that the tumor cells of the normal control group are tightly attached to the bottom of the bottle, the cells are dense, the connection between the cells is tight, the cells are in a regular polygon shape, the cell tentacles are short, and the round cells are few. NaW₁₂After LEP treatment, cells were sparse, loose with adnexa, detached, and rounded; see in particular fig. 7 to 8; FIG. 7 is an inverted microscope NaW₁₂-cell morphology change profile of LEP-treated HepG2, wherein a: a control group; b: 50. mu. mol. L^-1(ii) a Drawing (A)NaW under 8-stage inverted microscope₁₂-morphogram of LEP-treated HeLa cells, where a: a control group; b: 50. mu. mol. L^-1。

3. Paratungstate nano material (NaW)₁₂Comparative example of Synthesis of-LEP)

0.84g of stearic acid is dissolved in 11ml of absolute ethanol, the mixture is placed in a beaker and heated to 65 ℃ in a magnetic stirrer, and NaOH (0.51 g of NaOH solid is weighed and dissolved in 11ml of distilled water) solution is gradually dripped into the beaker and stirred continuously (the operation step is also under a heating state) until the colorless mixed solution becomes transparent. NaW will be mixed₁₂(3g in 28ml water) was dissolved in preheated distilled water and added to a beaker by infusion (repeated experiments using a microfiltration membrane placed in front of the injection needle) to determine a pH of 7-8. 0.32g of NaCl solid was weighed out and dissolved in 3ml of distilled water, and added to a beaker, and the pH was adjusted to about 8 to form a white suspension. After reacting for two hours at normal temperature on a magnetic stirrer, standing the suspension for three hours, and detecting to find the obtained composite material.

3 conclusion

The experiment takes the paratungstate as the raw material to synthesize the nano material, provides specific steps and detailed parameters for preparing the nano material, fills the blank of research on the paratungstate nano particle antitumor drugs, provides experimental data with extremely high application value for the antitumor activity of the polyacid drugs, and enables the polyacid drugs to have wider application prospect. Sodium stearate is used as a carrier to prepare the sodium paratungstate anti-tumor drug nano particles. Effects NaW₁₂Factors for LEP preparation include: proportioning ratio, pH value, temperature, dropping speed and drying mode. When reacting, NaW₁₂The concentration of the aqueous solution is 0.017g/ml, the dropping speed is about 40d/min, after suspension is generated, the dropping speed is reduced to 20d/min, finally the pH value of the reaction solution is adjusted to 4, and the reaction solution is dried in an oven at 50-60 ℃. Obtained NaW₁₂The LEP maintains the structure of parent polyacid and forms nanoparticles with the size of 200-1000 nm.

Adopts MTT method pair NaW₁₂The pharmacological properties of the LEP are researched, and the LEP is found to be capable of inhibiting human cervical carcinoma cells HeLa and human liver cancer HepG2 cell and human vascular endothelial EVC-304 cell proliferation, and is dose-dependent, and has half inhibitory concentration IC on proliferation₅₀The values were 3.42. mu. mol. L, respectively^-1，48.4μmol·L^-1And 62.7. mu. mol. L^-1. With parent polyacid NaW₁₂Compared with the nano-particle type polyacid drug transfersome, the antitumor activity of the nano-particle type polyacid drug transfersome is obviously enhanced.

The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.

Claims (10)

1. An paratungstate nanomaterial comprising: an paratungstate and a carrier;

wherein the paratungstate is Na₁₀H₂W₁₂O₄₂·26H₂O; the carrier is sodium stearate.

2. The paratungstate nanomaterial according to claim 1, wherein the particle size of the paratungstate nanoparticles is 200-1000 nm.

3. A preparation method of an paratungstate nano material comprises the following steps:

1) mixing Na₁₀H₂W₁₂O₄₂·26H₂Injecting the water solution of O into the sodium stearate solution, and adding a sodium chloride solution to obtain a mixed solution;

2) and regulating the pH value of the obtained mixed solution to 3.5-4.5 by using hydrochloric acid, and carrying out mixing reaction to obtain the paratungstate nano material.

4. The method according to claim 3, wherein the Na is₁₀H₂W₁₂O₄₂·26H₂The concentration of the O aqueous solution is 0.08-0.15 g/mL.

5. The method of claim 3, wherein the sodium stearate solution is prepared by the following method:

heating an ethanol solution of stearic acid to 55-85 ℃, and then dripping a sodium hydroxide solution into the solution until the solution is colorless and transparent to obtain a sodium stearate solution.

6. The method according to claim 5, wherein the concentration of the ethanol solution of stearic acid is 0.05 to 0.1 g/mL.

7. The method according to claim 5, wherein the stearic acid is reacted with the Na₁₀H₂W₁₂O₄₂·26H₂The mass ratio of O is (0.2-0.35) to 1.

8. The method according to claim 1, wherein the sodium chloride is mixed with the Na₁₀H₂W₁₂O₄₂·26H₂The mass ratio of O is (0.08-0.12) to 1.

9. The method according to claim 1, wherein the pH of the mixture in step 2) is adjusted to 3.8 to 4.2.

10. The use of the mesotungstate nanometer material as set forth in any one of claims 1-2 in preparation of antitumor drugs.

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