Strontium peroxide nano material as well as preparation method and application thereof

Abstract

The invention relates to a strontium peroxide nano-material, which is characterized in that a strontium source, alkali and hydrogen peroxide are used as raw materials, a mixed solution of an organic solvent and water is used as a reaction solvent, the strontium peroxide nano-material is prepared under a template or template-free condition, and the strontium peroxide nano-material can quickly react with water to generate hydroxyl, hydrogen peroxide and oxygen, hydrogen peroxide can achieve a tumor cell killing effect, hydroxyl can neutralize an acidic tumor microenvironment and alkalify tumor cells, and oxygen can relieve a hypoxic tumor microenvironment. In addition, the strontium peroxide nano material can induce macrophages to be polarized to an anti-tumor M1 type by regulating and controlling glycometabolism of the macrophages, and remodeling an intra-tumor lactic acid metabolism crosstalk mode. The strontium peroxide nano-material or the modified material and the preparation thereof can be directly injected into a tumor or near the tumor under ultrasonic guidance to realize in-situ treatment, or can be delivered to a tumor supply blood vessel through a catheter to realize embolism treatment, so that the strontium peroxide nano-material or the modified material and the preparation thereof have a certain application prospect in the field of tumor treatment.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a strontium peroxide nanomaterial and a preparation method and application thereof. The strontium peroxide nanomaterial has high reactivity and can produce alkali, oxygen and hydrogen peroxide at the same time. Background Art

[0002] Strontium peroxide, with the chemical formula SrO2, can react with water to produce hydroxide, hydrogen peroxide and oxygen, and the strontium hydroxide produced has a stronger alkalinity than calcium peroxide. Nanomaterials have a large specific surface area, higher reactivity, and are easy to modify and modify. They are increasingly used in the biomedical field, especially in the field of tumor treatment.

[0003] There are many methods for synthesizing strontium peroxide analogs of calcium peroxide nanomaterials, but the synthesis of nanoscale strontium peroxide materials is still limited to complicated processes and harsh conditions. For example, in 2023, Kandel et al. (R.Kandel, SRJang, U.Ghimire, S.Shrestha, BKShrestha, CHPark, CSKim. Engineered nanostructure fibrous cell-laden biointerfaces integrating Fe3O4 / SrO2-fMWCNTs induce osteogenesis and anti-bacterial effect, J. Ind. Eng. Chem., 2023, 120, 216-230.) A strontium peroxide nanomaterial was synthesized by liquid phase synthesis and then calcination at 600°C using strontium carbonate and sodium hydroxide as raw materials; in 2019, Zhang Meng et al. (patent number: CN110859820A) disclosed a biocompatible alkaline earth metal peroxide nanoformulation, a preparation method and its application. The method described is a one-step aqueous phase synthesis method at room temperature, that is, an alkaline earth metal peroxide nanoformulation coated with sodium hyaluronate is directly prepared in a water-alcohol mixed solvent system. However, in this method, most strontium salts are insoluble in alcohol solutions, and the reaction intermediate strontium hydroxide in the preparation process has high solubility and is difficult to precipitate crystal nuclei under room temperature conditions. Therefore, it is difficult to synthesize strontium peroxide nanoparticles in a room temperature, water-alcohol mixed system.

[0004] Therefore, in general, there is no report on the full liquid phase synthesis method of strontium peroxide nanomaterials with relatively mild reaction conditions, and the high reactivity of nanoscale strontium peroxide materials also determines that they are more likely to degrade into other products when exposed to moisture during the synthesis and storage process. Summary of the invention

[0005] In order to overcome at least one problem existing in the prior art, the present invention provides a strontium peroxide nanomaterial and its preparation method and application. The strontium peroxide nanomaterial is uniform in size and is synthesized in a liquid phase under ice bath conditions. The synthesis method is simple, the conditions are mild, and it is easy to store. It has been verified that the above-mentioned strontium peroxide nanomaterial cannot be successfully prepared under normal temperature conditions. The above-mentioned strontium peroxide nanomaterial can react rapidly with water to generate hydroxide, hydrogen peroxide and oxygen, wherein hydrogen peroxide can achieve a tumor cell killing effect, hydroxide can neutralize the acidic tumor microenvironment and alkalize the tumor cells, and oxygen can alleviate the hypoxic tumor microenvironment, thereby ultimately achieving the effect of tumor treatment. The present invention also provides a surface modification method of the strontium peroxide nanomaterial, which can modify the lipophilic oleic acid group on the surface of the strontium peroxide nanomaterial to facilitate the subsequent biomedical application of the material. The present invention also discloses a strontium peroxide nanomaterial dispersion preparation and a synthesis method thereof. The dispersion preparation can be injected into a tumor to achieve in situ treatment, or delivered to a tumor supply vessel via a catheter to achieve embolization treatment, and has certain application prospects in the field of tumor treatment.

[0006] To achieve the above object, the present invention adopts the following technical solution:

[0007] The first aspect of the present invention is to provide a strontium peroxide nanomaterial, the chemical formula of which is SrO2.

[0008] Furthermore, the average particle size of the strontium peroxide nanomaterial is 5 to 500 nm.

[0009] Furthermore, the strontium peroxide nanomaterial is a spherical nanoparticle with an average particle size of 5 to 50 nm. In a specific embodiment, the average particle size of the strontium peroxide nanomaterial is 8 nm.

[0010] Furthermore, the strontium peroxide nanomaterial has high reactivity and can produce alkali, oxygen and hydrogen peroxide at the same time. Specifically, the strontium peroxide nanomaterial reacts with water (acidic, neutral or alkaline conditions are all possible) to produce alkali, oxygen and hydrogen peroxide at the same time, and the chemical reaction formula is as follows:

[0011] SrO2+H2O→Sr(OH)2+H2O2+O2.

[0012] The second aspect of the present invention is to provide a method for preparing any strontium peroxide nanomaterial described in the first aspect of the present invention, which uses a strontium source, an alkali and hydrogen peroxide as raw materials, a mixed solution of an organic solvent and water as a reaction solvent, and prepares the strontium peroxide nanomaterial under the condition of having a template or not having a template.

[0013] Furthermore, the preparation method lowers the system temperature so that the strontium hydroxide intermediate of strontium peroxide with high solubility in the room temperature solution can be uniformly precipitated and nucleated in the mixed phase of water and organic solvent, so as to facilitate the subsequent uniform etching of strontium hydroxide crystal nuclei by hydrogen peroxide and the uniform generation of strontium peroxide, and at the same time inhibit the water in the mixed solution system from hydrolyzing the generated strontium peroxide to reduce impurities. The main advantage of the preparation method is the one-step synthesis of the entire liquid phase under ice bath conditions.

[0014] Furthermore, the preparation method comprises:

[0015] Step S1, dissolving a strontium source in deionized water without a template to obtain a strontium source solution of a predetermined concentration; or, dissolving a strontium source and a template in deionized water to obtain a strontium source solution of a predetermined concentration;

[0016] Step S2, precooling the mixed solution of the organic solvent and water in an ice bath, and then adding the strontium source solution and hydrogen peroxide obtained in step S1 to obtain a strontium source mixed solution;

[0017] Step S3, dissolving the alkali in deionized water to obtain an alkali solution of a predetermined concentration, and adding the alkali solution to the strontium source mixed solution obtained in step S2, reacting in an ice bath for a predetermined time, centrifuging once, washing the precipitate, centrifuging twice to obtain the supernatant, and then vacuum drying to obtain the strontium peroxide nanomaterial.

[0018] Furthermore, in step S1, the strontium source is selected from at least one of strontium nitrate and strontium chloride, preferably strontium nitrate.

[0019] Furthermore, in step S1, the template is selected from at least one of polyvinyl pyrrolidone, Pluronic F127 or polyvinyl alcohol, preferably polyvinyl pyrrolidone (PVP, molecular weight of 3 to 100 kDa).

[0020] Furthermore, in the step S1, under the condition of no template, the concentration of the strontium source solution is 0.1-10M, preferably 0.5-5M, more preferably 2M.

[0021] Furthermore, in the step S1, under the condition of a template, the mass ratio of the strontium source to the template is 0.02 to 4:1.

[0022] Furthermore, the operation of dissolving the strontium source and the template in deionized water is to dissolve them separately into a strontium source aqueous solution and a template aqueous solution in steps and then mix them, wherein the concentration of the strontium source aqueous solution is 0.5 to 10M, preferably 1 to 5M; the concentration of the template aqueous solution is 100 to 500 mg / mL, preferably 200 to 400 mg / mL. In a specific operation scheme, the strontium source is dissolved in deionized water to form a strontium source aqueous solution with a concentration of 2M; PVP (molecular weight of 10kDa) is dissolved in deionized water to form a PVP aqueous solution with a concentration of 250 mg / mL; and then the strontium source aqueous solution and the PVP aqueous solution are mixed at a volume ratio of 1:4.

[0023] Furthermore, in step S2, the organic solvent is selected from at least one of acetone and ethanol. Specifically, acetone is preferred under the condition of no template, and ethanol is preferred under the condition of having a template.

[0024] Furthermore, in the step S2, the hydrogen peroxide is 30% hydrogen peroxide.

[0025] Furthermore, in step S2, the volume ratio of the organic solvent to water is 1 to 30:1; preferably, the volume ratio is 5 to 30:1, and more preferably, the volume ratio is 5 to 11:1 (volume ratio of acetone to water) and 15 to 30:1 (volume ratio of ethanol to water). In a specific embodiment, under the condition of no template, the volume ratio of acetone to water is 11:1; under the condition of having a template, the volume ratio of ethanol to water is 30:1.

[0026] Furthermore, in step S2, the volume ratio of the strontium source solution to hydrogen peroxide is 0.5 to 4:1; preferably, the volume ratio is 0.5 to 2:1, and more preferably, the volume ratio is 1:1.

[0027] Furthermore, in step S2, the hydrogen peroxide and strontium source solution are added by stirring and dropping, specifically, the strontium source solution and hydrogen peroxide are stirred and dropped into the mixed solution of organic solvent and water respectively, wherein the stirring time is 5 to 15 minutes, preferably 10 minutes.

[0028] Furthermore, in step S2, the precooling time is 5 to 15 minutes, preferably 10 minutes.

[0029] Furthermore, in step S3, the base is selected from at least one of sodium hydroxide, potassium hydroxide and ammonia water; preferably, the base is sodium hydroxide.

[0030] Furthermore, in step S3, the concentration of the alkaline solution is 0.1-10M; preferably, the concentration is 0.1-5M, and more preferably, the concentration is 2M.

[0031] Furthermore, in step S3, the volume ratio of the alkaline solution to the strontium source solution is 1 to 6:1, preferably 2 to 4:1.

[0032] Furthermore, in step S3, the alkaline solution is added by slow dripping. In a specific embodiment, a syringe pump is used to slowly drip the alkaline solution at a speed of 12 mL / h.

[0033] Furthermore, in step S3, the ice bath reaction time is 0.5 to 4 hours, preferably 0.5 to 2 hours.

[0034] Furthermore, in step S3, the centrifugation condition is 10000-15000 rpm for 8-15 minutes; preferably 12000 rpm for 10 minutes.

[0035] Furthermore, in step S3, the precipitate is washed with anhydrous ethanol for 2 to 4 times; preferably, it is washed with anhydrous ethanol for 3 times.

[0036] Furthermore, in step S3, the secondary centrifugation condition is low-speed centrifugation at 1200-2000 rpm for 3-15 minutes; preferably low-speed centrifugation at 1500 rpm for 5-10 minutes, and more preferably low-speed centrifugation at 1500 rpm for 8 minutes.

[0037] Furthermore, in step S2 and step S3, under the ice bath conditions, the ambient temperature in the ice bath device is -2±2°C.

[0038] Furthermore, in step S3, the vacuum drying adopts conventional operating conditions in the art, and the specific conditions are related to the setting parameters of the vacuum drying oven.

[0039] The third aspect of the present invention is to provide a product prepared from strontium peroxide nanomaterials, wherein the strontium peroxide nanomaterials are as described in any one of the first aspects of the present invention or are prepared by any one of the preparation methods described in any one of the second aspects of the present invention.

[0040] Furthermore, the product includes modified strontium peroxide nanomaterials (the surface of the material is modified) and strontium peroxide nanomaterial dispersion preparations.

[0041] Furthermore, the preparation method of the modified strontium peroxide nanomaterial comprises: modifying the lipophilic oleic acid group on the surface of the strontium peroxide nanomaterial, and the strontium peroxide will not undergo degradation reaction during the modification process. The above modification is achieved through the strong interaction between the phosphate group and the strontium ion.

[0042] Furthermore, the preparation method of the modified strontium peroxide nanomaterial specifically comprises:

[0043] Step A, adding an ethanol dispersion of strontium peroxide nanomaterials into a chloroform solution of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid to obtain a mixed dispersion of strontium peroxide and sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid;

[0044] Step B: subjecting the mixed dispersion obtained in step A to water bath ultrasonic treatment, and then washing with chloroform to obtain sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid modified strontium peroxide nanomaterial.

[0045] Furthermore, in the step A, the concentration of strontium peroxide in the ethanol dispersion of the strontium peroxide nanomaterial is 0.5 to 10 mg / mL, preferably 4 to 8 mg / mL, and more preferably 5 mg / mL.

[0046] Furthermore, in the step A, the concentration of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid in the chloroform solution is 0.5 to 50 mg / mL; preferably 5 to 30 mg / mL, more preferably 10 mg / mL.

[0047] Furthermore, in the step A, in the mixed dispersion, the concentration ratio of strontium peroxide to sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid is 1:0.5-10; preferably, the concentration ratio is 1:1-4, and more preferably, the concentration ratio is 1:2.

[0048] Furthermore, in step A, the two solutions are mixed by dropping the ethanol dispersion of the strontium peroxide nanomaterial into the stirring chloroform solution of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid. The dropping and stirring here adopts conventional operating conditions in the art.

[0049] Furthermore, in step B, the conditions for water bath ultrasonic treatment are: water bath ultrasonic treatment in an ultrasonic cleaning apparatus for 0.5 to 4 hours; preferably water bath ultrasonic treatment for 2 hours.

[0050] Furthermore, the strontium peroxide nanomaterial dispersion preparation is composed of strontium peroxide nanomaterial or modified strontium peroxide nanomaterial and a dispersion liquid.

[0051] Furthermore, the preparation method of the strontium peroxide nanomaterial dispersion comprises:

[0052] The ethanol dispersion of strontium peroxide nanomaterial or modified strontium peroxide nanomaterial is centrifuged to discard the supernatant, and then a special solvent for dispersion preparation is added to the precipitate and then ultrasonicated in a water bath to obtain a strontium peroxide nanomaterial dispersion preparation.

[0053] Furthermore, in the strontium peroxide nanomaterial dispersion, the concentration of the strontium peroxide nanomaterial or the modified strontium peroxide nanomaterial is 1-400 mM, and the preferred concentration is 200 mM. If the concentration is lower, the amount of alkali, oxygen and hydrogen peroxide produced is lower, and the cell killing effect is not obvious.

[0054] Furthermore, in the ethanol dispersion, the concentration of the strontium peroxide nanomaterial or the modified strontium peroxide nanomaterial is 0.1 to 50 mg / mL, preferably 1 to 20 mg / mL, and more preferably 5 mg / mL.

[0055] Furthermore, the special solvent for the dispersion preparation is at least one of short-chain polyethylene glycol and iodized oil, wherein the number average molecular weight of the short-chain polyethylene glycol is 200 to 600 Da, and the iodized oil is purchased commercially.

[0056] Furthermore, the centrifugation condition is 10000-15000 rpm for 8-20 minutes; preferably 12000 rpm for 10 minutes.

[0057] Furthermore, the water bath ultrasound duration is 5 to 30 minutes.

[0058] The fourth aspect of the present invention is to provide a strontium peroxide nanomaterial or a product prepared therefrom for use in the preparation of anti-tumor drugs, wherein the strontium peroxide nanomaterial is as described in any one of the first aspects of the present invention or is prepared by any one of the preparation methods described in any one of the second aspects of the present invention, and the product is as described in any one of the third aspects of the present invention.

[0059] Furthermore, the anti-tumor drug is a drug that can achieve tumor cell killing effects, neutralize the acidic tumor microenvironment, alkalize tumor cells, and alleviate the hypoxic tumor microenvironment.

[0060] Furthermore, the anti-tumor drug is a drug that regulates macrophage glucose metabolism to induce macrophage polarization to the anti-tumor M1 type and reshape the intratumoral lactate metabolic crosstalk pattern.

[0061] Furthermore, the strontium peroxide nanomaterial or products prepared therefrom (modified materials, dispersed preparations, etc.) can be injected into the tumor or adjacent to the tumor directly or guided by imaging methods such as ultrasound imaging to achieve in situ treatment, or delivered to the tumor supply vessels via a catheter to achieve embolization treatment.

[0062] Furthermore, the tumor includes benign tumors and malignant tumors. The benign tumors include hemangioma, lymphangioma, fibroma, lipoma, neurogenic tumor, teratoma, carotid body tumor, uterine fibroids, etc., and the malignant tumors include esophageal cancer, gastric cancer, rectal cancer, colon cancer, nasopharyngeal cancer, liver cancer, lung cancer, cervical cancer, breast cancer, etc.

[0063] Furthermore, the strontium peroxide nanomaterial or a product prepared therefrom is delivered to liver cancer lesions by in situ puncture under ultrasound guidance to achieve chemical ablation treatment.

[0064] Compared with the prior art, the present invention adopts the above technical solution to have the following beneficial effects:

[0065] The present invention discloses a one-step synthesis method for preparing strontium peroxide nanomaterials in an all-liquid phase ice bath, which reduces the solubility at low temperature to promote the precipitation of strontium hydroxide and further the formation of strontium peroxide crystal nuclei and inhibit the hydrolysis of products. The method has the advantages of simple preparation process, mild reaction conditions, no requirement for the introduction of template molecules, and uniform and pure products. The specific advantages are as follows:

[0066] (1) Compared with ordinary strontium peroxide powder on the market, nano-sized strontium peroxide particles have a larger specific surface area, greater reactivity and faster reaction rate. Their nanoscale size is also conducive to in vivo biomedical applications;

[0067] (2) The present invention uses an ice bath synthesis method to synthesize pure strontium peroxide nanomaterials in a liquid phase system for the first time. The template is optional, and the particle size of the product can be controlled by adjusting the reaction time and the amount of alkali added. The particle size of the product can be increased by appropriately extending the reaction time or increasing the amount of alkali added. The ethanol dispersibility is good, and the reaction activity is significantly improved compared to the common metal peroxide CaO2. It can react chemically with water rapidly to generate a large amount of hydroxide, oxygen and hydrogen peroxide.

[0068] (3) The present invention innovatively uses sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid to modify the surface of strontium peroxide nanomaterials, thereby improving the dispersibility of strontium peroxide nanomaterials (with a small average particle size of about 5 to 50 nm and not prone to sedimentation) in oily dispersions such as iodized oil, thereby facilitating the storage of strontium peroxide nanomaterials;

[0069] (4) The strontium peroxide nanomaterials, strontium peroxide nanomaterial dispersions, and sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid-modified strontium peroxide nanomaterial dispersions provided by the present invention have not been reported in the field of anti-tumor applications. The large amount of hydroxide and hydrogen peroxide generated by strontium peroxide in the tumor area in a short period of time can quickly kill tumor cells and achieve an anti-tumor effect; strontium peroxide nanomaterials can also regulate macrophage sugar metabolism to induce macrophages to polarize toward the anti-tumor M1 type, and reshape intratumoral lactate metabolism crosstalk to improve the immunosuppressive microenvironment of the tumor;

[0070] (5) The nanoreagent of the present invention is simple to prepare, and the raw materials are cheap and readily available, and can be widely used in the preparation of cancer drugs in vivo. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] The drawings described herein are used to provide a further understanding of the present invention and constitute a part of the present invention. The exemplary embodiments of the present invention and their descriptions are only used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0072] Figure 1 is a transmission electron microscopy image of SPNs (template-free strontium peroxide nanomaterials) in one embodiment of the present invention;

[0073] Figure 2 is the particle size statistics result in the transmission electron microscopy image of SPNs in one embodiment of the present invention;

[0074] Figure 3 is the X-ray diffraction pattern of SPNs in one embodiment of the present invention and the standard spectrum of SrO2 (PDF#07-0234);

[0075] Figure 4 is a transmission electron microscopic image of SPNs (i.e., SPN-1 described in Example 1) obtained after adjusting the ratio of organic solvent to water in the reaction environment in one embodiment of the present invention;

[0076] Figure 5 It is the X-ray diffraction pattern of SPNs (i.e., SPN-1 described in Example 1) obtained after adjusting the ratio of organic solvent to water in the reaction environment in one embodiment of the present invention and the standard spectrum line corresponding to SrO2 (PDF#07-0234);

[0077] Figure 6 is a transmission electron microscopic image of the SPNs (i.e., SPN-2 described in Example 1) obtained after adjusting the reaction time in one embodiment of the present invention;

[0078] Figure 7 The X-ray diffraction patterns of the SPNs obtained after adjusting the reaction time in one embodiment of the present invention (i.e., SPN-2 described in Example 1) and the SPNs obtained after adjusting the alkali dosage (i.e., SPN-3 described in Example 1) and the standard spectrum corresponding to SrO2 (PDF#07-0234);

[0079] Figure 8 is a transmission electron microscopic image of SPNs (i.e., SPN-3 described in Example 1) obtained after adjusting the alkali dosage in one embodiment of the present invention;

[0080] Fig. 9 It is a transmission electron microscopy image of SrO2@PVP (strontium peroxide nanomaterial with PVP as template) in one embodiment of the present invention;

[0081] Fig.10This is a transmission electron microscopy image of SPN@DOPA (strontium peroxide nanomaterial modified by sodium dioleoylphosphatidylcholine) in one embodiment of the present invention;

[0082] Fig.11 is an energy dispersive element distribution image of SPN@DOPA in one embodiment of the present invention;

[0083] Fig.12 is the H2O2 yield after the SPNs react in different media at a concentration of 5 mM in one embodiment of the present invention;

[0084] Fig.13 It is the pH change of the medium within 600 seconds after SPNs reacted in different media at a concentration of 5 mM in one embodiment of the present invention;

[0085] Fig.14 is an optical microscopic image of a large number of bubbles generated by SPNs in deionized water at a concentration of 10 mM in one embodiment of the present invention;

[0086] Fig.15 This is the toxicity evaluation result of SPNs on mouse liver cancer cells in one embodiment of the present invention;

[0087] Fig.16 This is the toxicity evaluation result of SrO2@PVP on mouse liver cancer cells in one embodiment of the present invention;

[0088] Fig.17 The inhibitory effect of the strontium peroxide nanomaterial dispersion preparation SPN@PEG (polyethylene glycol dispersion of strontium peroxide nanomaterial) in one embodiment of the present invention and the control group, Sr(OH)2 and H2O2 on the tumor volume in a mouse subcutaneous liver cancer tumor model;

[0089] Fig.18 These are the flow cytometry results of SPNs and a control group, Sr(OH)2 and H2O2 inducing bone marrow-derived macrophage (BMDM) polarization in an ordinary environment and a simulated environment containing lactic acid, respectively, in an embodiment of the present invention. DETAILED DESCRIPTION

[0090] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without creative work belong to the scope of protection of the present invention. The experimental methods without specific conditions in the following embodiments are usually measured according to national standards. The experimental materials without the source indicated in the following embodiments are all commercially available raw materials. The equipment used in each step in the following embodiments is conventional equipment. If there is no corresponding national standard, it is carried out according to the general international standards, conventional conditions, or according to the conditions recommended by the manufacturer. Unless otherwise specified, all parts are weight parts and all percentages are mass percentages. Unless otherwise defined or specified, all professional and scientific terms used in the present invention have the same meaning as those familiar to those skilled in the art. In addition, any method and material similar or equal to the recorded content can be applied to the method of the present invention.

[0091] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other. The present invention is further described below in conjunction with the drawings and specific embodiments, but is not intended to be a limitation of the present invention.

[0092] In certain specific embodiments of the present invention, the preparation method of strontium peroxide nanomaterials comprises the following steps: (1) dissolving a strontium source in deionized water without a template to obtain a strontium source solution with a concentration of 0.1 to 10 M; or, dissolving a strontium source and a template in deionized water at a mass ratio of 0.02 to 4 to obtain a strontium source solution with a template, specifically, first dissolving the strontium source and the template separately into a strontium source aqueous solution and a template aqueous solution and then mixing them, wherein the concentration of the strontium source aqueous solution is 0.5 to 10 M, and the concentration of the template aqueous solution is 100 to 500 mg / mL; (2) placing a mixed solution of an organic solvent and water in a volume ratio of 1 to 30:1 in an ice bath for preheating. After cooling for 5 to 15 minutes, adding a strontium source solution and 30% hydrogen peroxide dropwise with stirring, the volume ratio of the strontium source solution to hydrogen peroxide being 0.5 to 4:1, to obtain a strontium source mixed solution; (3) dissolving an alkali in deionized water to obtain an alkali solution with a concentration of 0.1 to 10M, and slowly adding the alkali solution to the strontium source mixed solution dropwise, the volume ratio of the alkali solution to the strontium source solution being 1 to 6:1, reacting in an ice bath for 0.5 to 4 hours, centrifuging at 10000 to 15000 rpm for 8 to 15 minutes, washing the precipitate with anhydrous ethanol for 2 to 4 times, centrifuging at a low speed of 1200 to 2000 rpm for 3 to 15 minutes, taking the supernatant, and vacuum drying to obtain the strontium peroxide nanomaterial.

[0093] In certain specific embodiments of the present invention, the strontium source is selected from at least one of strontium nitrate and strontium chloride; the template is selected from at least one of polyvinyl pyrrolidone, Pluronic F127 or polyvinyl alcohol; the organic solvent is selected from at least one of acetone and ethanol; the alkali is selected from at least one of sodium hydroxide, potassium hydroxide or ammonia water; under the ice bath conditions, the ambient temperature in the ice bath device is -2±2°C.

[0094] In certain specific embodiments of the present invention, the chemical formula of the strontium peroxide nanomaterial prepared by the above preparation method is SrO2, and its average particle size is 5 to 500 nm.

[0095] Strontium peroxide nanomaterials can be successfully prepared under the above-mentioned raw material ratios and operating parameters, but there are differences in particle size, ethanol dispersibility, reaction activity, anti-tumor effect, etc.

[0096] In certain specific embodiments of the present invention, a method for preparing a modified strontium peroxide nanomaterial (a method for modifying the surface of a strontium peroxide nanomaterial) comprises the following steps: (1) adding an ethanol dispersion of the strontium peroxide nanomaterial (at a concentration of 0.5 to 10 mg / mL) to a stirred chloroform solution of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid (at a concentration of 0.5 to 50 mg / mL) to obtain a mixed dispersion of strontium peroxide and sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid, wherein the concentration ratio of strontium peroxide to sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid is 1:0.5 to 10; (2) subjecting the obtained mixed dispersion to water bath ultrasonic treatment for 0.5 to 4 hours in an ultrasonic cleaning apparatus, and then washing with chloroform to obtain a strontium peroxide nanomaterial modified with sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid.

[0097] Under the above-mentioned range of raw material ratios and operating parameters, modified strontium peroxide nanomaterials can be successfully prepared, but there are differences in the degree of modification, dispersibility in oily dispersions, anti-tumor effects, etc.

[0098] In certain specific embodiments of the present invention, the preparation of a strontium peroxide nanomaterial dispersion comprises the steps of: centrifuging an ethanol dispersion of a strontium peroxide nanomaterial or a modified strontium peroxide nanomaterial having a concentration of 0.1 to 50 mg / mL at 10,000 to 15,000 rpm for 8 to 20 minutes, discarding the supernatant, adding a special solvent for the dispersion (short-chain polyethylene glycol, iodized oil) to the precipitate so that the strontium peroxide concentration in the dispersion is 1 to 400 mM, and then ultrasonicating in a water bath for 5 to 30 minutes to obtain a strontium peroxide nanomaterial dispersion.

[0099] Under the above-mentioned range of raw material ratios and operating parameters, strontium peroxide nanomaterial dispersion preparations can be successfully prepared, but there are differences in material dispersibility, anti-tumor effect, etc.

[0100] In certain specific preparation embodiments of the present invention, the above-mentioned raw material ratios and process parameters are optimized and selected, thereby obtaining materials with excellent performance and good anti-tumor effects.

[0101] In the following examples, the raw materials strontium nitrate (Sr(NO3)2, Shanghai test), sodium hydroxide (NaOH, Aladdin), hydrogen peroxide (30% H2O2, Shanghai test), acetone (Sinopharm), ethanol (Aladdin), polyvinylpyrrolidone (PVP, Aladdin), sodium dioleoylphosphatidylcholine (DOPA, Langxu Biotechnology), polyethylene glycol (PEG, Aladdin) and iodized oil (IO, such as poppy ethiodized oil (Hengrui)) can all be obtained commercially.

[0102] Example 1 - Synthesis of template-free strontium peroxide nanomaterials

[0103] This embodiment provides a better template-free method for synthesizing strontium peroxide nanomaterials and adjusts some process conditions on the method. The above methods can successfully prepare strontium peroxide nanomaterials.

[0104] (1) A template-free synthesis method of strontium peroxide nanomaterials;

[0105] Step 1: Mix 55 mL of acetone with 5 mL of deionized water to obtain an acetone / water mixed solution, and precool it in an ice bath (temperature is –2±2°C) for 10 minutes;

[0106] Step 2: In an ice bath, add 1 mL of Sr(NO3)2 aqueous solution (2M) and then add 1 mL of H2O2 (mass fraction: 30%) to the acetone / water mixed solution in step 1 with stirring, and stir for 10 minutes;

[0107] Step 3: In an ice bath, 2 mL of NaOH (2M) was slowly added to the final system of step 2 at a rate of 12 mL / h using a syringe pump, and stirring was continued for 0.5 hours after the addition was completed; after centrifugation at 12000 rpm for 10 minutes, the precipitate was washed three times with anhydrous ethanol, and after centrifugation at 1500 rpm for 8 minutes, the supernatant was taken and vacuum dried to obtain strontium peroxide nanomaterials.

[0108] The strontium peroxide nanomaterials obtained by the above method are denoted as SPNs, and their transmission electron microscopy images and statistical results are shown in Figure 1 and Figure 2 Its X-ray diffraction pattern is shown in Figure 3 ,Depend on Figure 3 It can be obtained that the obtained nanomaterial component is SrO2.

[0109] (2) Based on the synthesis method described in (1), adjusting the process conditions;

[0110] The ratio of the acetone / water mixed solution was replaced with 50 mL acetone and 10 mL water, and the other steps and parameters remained unchanged. The obtained strontium peroxide nanomaterial was recorded as SPN-1, and its transmission electron microscopy image and X-ray diffraction spectrum were shown in Figure 4 and Figure 5 , it can be concluded that the sample composition is SrO2, which is spherical nanoparticles.

[0111] Alternatively, the stirring time in step 3 is replaced with 2 hours, and the other steps and parameters remain unchanged. The obtained strontium peroxide nanomaterial is recorded as SPN-2. Its transmission electron microscopy image is shown in Figure 6 It can be seen that the obtained product is spherical nanoparticles. The nanoparticles obtained by extending the reaction time have larger particle sizes. The X-ray diffraction pattern is shown in Figure 7 , it can be seen that the product is pure SrO2.

[0112] Alternatively, the NaOH dosage in step 3 was replaced with 4 mL, and the volume of deionized water in step 1 was reduced to 3 mL, while the other steps and parameters remained unchanged. The obtained strontium peroxide nanomaterial was recorded as SPN-3, and the transmission electron microscopy image was shown in Figure 8 It can be seen that the obtained product is spherical nanoparticles, and the nanoparticles obtained by increasing the NaOH dosage have larger particle sizes; its X-ray diffraction spectrum is shown in Figure 7 , it can be seen that the product is pure SrO2.

[0113] Example 2-Synthesis of Strontium Peroxide Nanomaterials Using PVP as Template

[0114] This embodiment is a preferred method for synthesizing strontium peroxide nanomaterials using PVP as a template, which includes the following steps:

[0115] The acetone in step 1 of Example 1 was replaced with ethanol, and its volume was changed to 60 mL. The water volume was replaced with 2 mL. The 1 mL Sr(NO3)2 aqueous solution (2M) in step 2 was changed to a mixed solution of 1 mL Sr(NO3)2 aqueous solution (2M) and 4 mL PVP aqueous solution (250 mg / mL) with a molecular weight of 10 kDa. The other reaction parameters were the same as those in Example 1.

[0116] The strontium peroxide nanomaterial obtained by the above method is denoted as SrO2@PVP, and its transmission electron microscopy image is shown in Fig. 9 , it can be seen that the product can be evenly dispersed in ethanol.

[0117] Example 3-Synthesis of Strontium Peroxide Nanomaterial Modified by Sodium Dioleoylphosphatide

[0118] This embodiment is a preferred method for synthesizing a strontium peroxide nanomaterial modified with sodium dioleoylphosphatide, which comprises the steps of:

[0119] Step 1: 6 mL of the ethanol dispersion of strontium oxide nanomaterial SPNs prepared in Example 1 (5 mg / mL) was added dropwise to 6 mL of a stirred chloroform solution of DOPA (10 mg / mL) to obtain a mixed dispersion of SPNs and sodium dioleoylphosphatidylcholine;

[0120] Step 2: The mixed dispersion of SPNs and sodium dioleoylphosphatide in step 1 is placed in an ultrasonic cleaning apparatus for water bath ultrasound for 2 hours, and then washed with chloroform twice to obtain a sodium dioleoylphosphatide-modified strontium peroxide nanomaterial.

[0121] The strontium peroxide nanomaterial modified with sodium dioleoylphosphatidyl alcohol obtained by the above method is denoted as SPN@DOPA, and its transmission electron microscopy image is shown in Fig.10 , it can be seen that the outer layer of the nanoparticles is coated with organic matter, indicating that sodium dioleoylphosphatide is successfully combined with the surface of strontium peroxide nanomaterials. The element distribution image is shown in Fig.11 It can be seen that the nanomaterial contains strontium and oxygen from strontium peroxide and phosphorus from sodium dioleoylphosphatidylcholine.

[0122] Example 4 - Synthesis of Dispersed Formulations of Strontium Peroxide Nanomaterials

[0123] This embodiment is a preferred method for synthesizing a polyethylene glycol dispersion preparation and an iodized oil dispersion preparation of strontium peroxide nanomaterial, which comprises the following steps:

[0124] (1) Take 4 mL of the ethanol dispersion (5 mg / mL) of the strontium oxide nanomaterial SPNs prepared in Example 1, centrifuge at 12000 rpm for 10 minutes and discard the supernatant, add 836 μL of polyethylene glycol (number average molecular weight: 200 Da) or iodized oil to the precipitate, and disperse in a water bath with ultrasonic waves to obtain the polyethylene glycol dispersion (denoted as SPN@PEG) or iodized oil dispersion (denoted as SPN@IO) of SPNs.

[0125] (2) The ethanol dispersion in (1) was replaced with 4 mL of the ethanol dispersion of SPN@DOPA (5 mg / mL) prepared in Example 3. The other operating conditions were the same as in (1) to obtain a polyethylene glycol dispersion or iodized oil dispersion of SPN@DOPA.

[0126] Example 5-Performance Verification of Strontium Peroxide Nanomaterials

[0127] This example verifies the hydrogen peroxide production capacity, alkali production capacity, and oxygen production capacity of the strontium oxide nanomaterial SPNs prepared in Example 1, and includes the following steps:

[0128] (1) Evaluation of the ability of SPNs to produce hydrogen peroxide in different media: 10 μL of SPNs ethanol dispersion (200 mM) was added to each of the five media, namely, 5 mL of deionized water, phosphate buffers with pH values ​​of 7.4, 6.5, and 5.0, and DMEM cell culture medium. After vortex mixing, the mixture was allowed to stand for 15 minutes to allow for a full reaction. Subsequently, 50 μL of the mixture was taken out from each of the above mixtures and the hydrogen peroxide concentration in the mixture was detected using a hydrogen peroxide detection kit. The results are shown in Fig.12 As can be seen from the figure, SPNs can quickly produce a large amount of hydrogen peroxide in the above media.

[0129] (2) To evaluate the ability of SPNs to generate alkali in different media, 125 μL of SPNs ethanol dispersion (200 mM) was added to 5 mL of deionized water, phosphate buffer with pH values ​​of 7.4, 6.5, and 5.0, and DMEM cell culture medium while stirring. A pH meter was used to detect changes in the medium pH from 0 to 600 seconds. The results are shown in Table 1. Fig.13 As can be seen from the figure, SPNs can quickly produce hydroxide in the above media and make the media quickly alkaline.

[0130] (3) To evaluate the oxygen production capacity of SPNs, 5 μL of SPNs ethanol dispersion (200 mM) was added to 100 μL of deionized water, and an inverted microscope was used to take pictures 5 minutes after adding SPNs. Fig.14 ,As can be seen from the figure, SPNs quickly generate a large number of oxygen bubbles in deionization.

[0131] Example 6-Verification of cytotoxicity of strontium peroxide nanomaterials

[0132] This example evaluates the cytotoxicity of strontium peroxide nanomaterials, and the method includes:

[0133] (1) Verification of the cytotoxicity of the strontium peroxide nanomaterial SPNs prepared in Example 1;

[0134] Hepa1-6 mouse liver cancer cells were plated at 5×10 4 The cells were inoculated at a density of 100 / mL in a 96-well plate. After culturing for 24 hours, they were incubated with SPNs or Sr(NO3)2 at concentrations of 0, 0.1, 0.25, 0.5, 0.75, 1, 1.25, 2.5, and 5 mM for 24 hours. Finally, the cytotoxicity was evaluated using a CCK detection kit according to the standard procedure described in the kit manual. The results are shown in the figure. Fig.15The experimental results showed that SPNs had concentration-dependent cytotoxicity, and the half-lethal concentration of SPNs for Hepa1-6 cells was between 1 and 1.25 mM. When the SPNs concentration was 2.5 mM, the cell killing rate could reach 100%, so it had excellent tumor cell killing ability.

[0135] (2) Verification of the cytotoxicity of the strontium peroxide nanomaterial SrO2@PVP prepared in Example 2;

[0136] The SPNs in (1) were replaced by SrO2@PVP, the Hepa1-6 mouse liver cancer cells were replaced by 4T1 mouse breast cancer cells, the concentrations were replaced by 0, 1, 5, 10, 25, 50, 75, 100, 250, 500 μg / mL, and the other processes and parameters were the same as those in Example 8. The results are shown in Fig.16 The experimental results showed that SrO2@PVP had concentration-dependent cytotoxicity, and its median lethal concentration for 4T1 cells was about 50 μg / mL. When the SrO2@PVP concentration was 100 μg / mL, the cell killing rate could reach 100%, so it had excellent tumor cell killing ability.

[0137] Example 7 - Evaluation of the in vivo anti-tumor effect of strontium peroxide nanomaterial dispersions

[0138] This example evaluates the in vivo anti-tumor effect of the strontium peroxide nanomaterial dispersion prepared in Example 4. 100 μL of a PBS suspension of Hepa1-6 cells (inoculation dose: 3*10 6 The average volume of subcutaneous tumors was about 120-150mm 7 days after inoculation. 3 At this time, drug injection and tumor observation began. SPN@PEG, PEG, Sr(OH)2 or H2O2 were injected intratumorally at a dose of 0.5 μmol / kg on days 0, 5 and 10, and the tumor volume of mice was measured every other day for 14 days. The tumor volume was calculated as follows: volume = 0.5 × length × width 2 , a total of two weeks of observation. The experimental results are shown in Fig.17 ,The data showed that on the 14th day, the average tumor volume of the SPN@PEG group was only 26.3% of that of the control group, so SPN@PEG can effectively inhibit tumor growth in mice.

[0139] Example 8-Evaluation of the effect of strontium peroxide nanomaterials on inducing macrophage polarization

[0140] This example evaluates the effect of SPNs prepared in Example 1 on inducing macrophage polarization. Bone marrow cells were extracted and separated from the tibia and femur of 6-week-old C57BL / 6J mice, and bone marrow-derived macrophages were obtained after induction with 20ng / mL M-CSF for 5 days. After 5 days, the culture medium was replaced with a normal culture medium containing 1.25mM SPNs, Sr(OH)2 or H2O2 or a culture medium containing 10mM L-lactic acid (denoted as LA), respectively. After 24h, the drug-treated BMDMs were stained with FVS 510, F4 / 80-FITC, CD86-APC and CD206-PE, and then single-cell fluorescence analysis was performed using a BD Fortessa flow cytometer. The experimental results are shown in Fig.18 The data showed that SPNs could increase the proportion of M1 macrophages and reduce the proportion of M2 macrophages in both normal culture environments and simulated tumor microenvironments containing lactic acid, and this trend was particularly enhanced in simulated tumor microenvironments containing lactic acid.

[0141] As can be seen from the above embodiments, the strontium peroxide nanomaterial prepared by the present invention is uniform in size and is synthesized in a liquid phase under ice bath conditions. The synthesis method is simple and the conditions are mild. The oleophilic oleic acid group can be modified on the surface of the above strontium peroxide nanomaterial. During the modification process, the strontium peroxide will not undergo degradation reaction. The above strontium peroxide nanomaterial or its modified material can also be prepared into a strontium peroxide nanomaterial dispersion. The above strontium peroxide nanomaterial can react rapidly with water to generate hydroxide, hydrogen peroxide and oxygen, wherein hydrogen peroxide can achieve the effect of killing tumor cells, hydroxide can neutralize the acidic tumor microenvironment and alkalize the tumor cells, and oxygen can alleviate the hypoxic tumor microenvironment, thereby ultimately achieving the effect of tumor treatment. The above strontium peroxide nanomaterial can also regulate macrophage sugar metabolism to induce macrophages to polarize to the anti-tumor M1 type and reshape the intratumoral lactate metabolism crosstalk pattern.

[0142] The specific embodiments of the present invention are described in detail above, but they are only examples, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions made to the present invention are also within the scope of the present invention. Therefore, the equalization changes and modifications made without departing from the spirit and scope of the present invention should be included in the scope of the present invention.

Claims

1. A strontium peroxide nanomaterial, characterized in that: The chemical formula of the strontium peroxide nanomaterial is SrO2, and its average particle size is 5 to 500 nm.

2. The strontium peroxide nanomaterial according to claim 1, characterized in that: The strontium peroxide nanomaterial is spherical nanoparticles with an average particle size of 5 to 50 nm.

3. The method for preparing a strontium peroxide nanomaterial according to any one of claims 1 to 2, characterized in that: The strontium peroxide nanomaterial is prepared by using a strontium source, alkali and hydrogen peroxide as raw materials and a mixed solution of an organic solvent and water as a reaction solvent under the condition of having a template or not having a template.

4. The preparation method according to claim 3, characterized in that: The preparation method comprises: Step S1, dissolving a strontium source in deionized water without a template to obtain a strontium source solution of a predetermined concentration; or, dissolving a strontium source and a template in deionized water to obtain a strontium source solution of a predetermined concentration; Step S2, precooling the mixed solution of the organic solvent and water in an ice bath, and then adding the strontium source solution and hydrogen peroxide obtained in step S1 to obtain a strontium source mixed solution; Step S3, dissolving the alkali in deionized water to obtain an alkali solution of a predetermined concentration, and adding the alkali solution to the strontium source mixed solution obtained in step S2, reacting in an ice bath for a predetermined time, centrifuging once, washing the precipitate, centrifuging twice to obtain the supernatant, and then vacuum drying to obtain the strontium peroxide nanomaterial.

5. The preparation method according to claim 4, characterized in that: In the step S1, The strontium source is selected from at least one of strontium nitrate and strontium chloride, and the template is selected from at least one of polyvinyl pyrrolidone, Pluronic F127 or polyvinyl alcohol; and / or, under the template-free condition, the concentration of the strontium source solution is 0.1 to 10 M; Or, under the condition of a template, the mass ratio of the strontium source to the template is 0.02-4, and the operation of dissolving the strontium source and the template in deionized water is to first dissolve them separately into a strontium source aqueous solution and a template aqueous solution and then mix them, the concentration of the strontium source aqueous solution is 0.5-10M, and the concentration of the template aqueous solution is 100-500mg / mL.

6. The preparation method according to claim 4, characterized in that: In the step S2, The organic solvent is selected from at least one of acetone and ethanol, and the hydrogen peroxide is 30% hydrogen peroxide; and / or the volume ratio of the organic solvent to water is 1 to 30:1, and the volume ratio of the strontium source solution to hydrogen peroxide is 0.5 to 4:1; And / or, the hydrogen peroxide and strontium source solution are added dropwise with stirring; And / or, under the ice bath conditions, the ambient temperature in the ice bath device is -2±2°C.

7. The preparation method according to claim 4, characterized in that: In the step S3, The alkali is selected from at least one of sodium hydroxide, potassium hydroxide and ammonia water; And / or, the concentration of the alkaline solution is 0.1 to 10 M; the volume ratio of the alkaline solution to the strontium source solution is 1 to 6:1; And / or, the alkaline solution is added by slow dropwise addition; And / or, the ice bath reaction time is 0.5 to 4 hours, the first centrifugation condition is 10000 to 15000 rpm for 8 to 15 minutes, the precipitate is washed with anhydrous ethanol for 2 to 4 times, and the second centrifugation condition is 1200 to 2000 rpm for 3 to 15 minutes; and / or, under the ice bath conditions, the ambient temperature in the ice bath device is -2±2°C.

8. A product prepared from strontium peroxide nanomaterial, characterized in that: The strontium peroxide nanomaterial is as described in any one of claims 1 to 2 or is prepared by the preparation method described in any one of claims 3 to 7.

9. The product according to claim 8, characterized in that The products include modified strontium peroxide nanomaterials and strontium peroxide nanomaterial dispersion preparations.

10. The product according to claim 9, characterized in that The preparation method of the modified strontium peroxide nanomaterial comprises: modifying the lipophilic oleic acid group on the surface of the strontium peroxide nanomaterial, and no degradation reaction will occur to the strontium peroxide during the modification process.

11. The product according to claim 10, characterized in that The preparation method of the modified strontium peroxide nanomaterial specifically comprises: Step A, adding an ethanol dispersion of strontium peroxide nanomaterials into a chloroform solution of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid to obtain a mixed dispersion of strontium peroxide and sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid; Step B: subjecting the mixed dispersion obtained in step A to water bath ultrasonic treatment, and then washing with chloroform to obtain sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid modified strontium peroxide nanomaterial.

12. The product according to claim 11, characterized in that In the step A, in the ethanol dispersion of the strontium peroxide nanomaterial, the concentration of strontium peroxide is 0.5-10 mg / mL; in the chloroform solution of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid, the concentration of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid is 0.5-50 mg / mL; in the mixed dispersion, the concentration ratio of strontium peroxide to sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid is 1:0.5-10; And / or, in step A, the two solutions are mixed by: adding the ethanol dispersion of the strontium peroxide nanomaterial dropwise to a stirring chloroform solution of sodium dioleoylphosphatidic acid or dioleoylphosphatidic acid; And / or, in step B, the conditions for water bath ultrasonic treatment are: water bath ultrasonic treatment in an ultrasonic cleaning apparatus for 0.5 to 4 hours.

13. The product according to claim 9, characterized in that The strontium peroxide nanomaterial dispersion preparation is composed of strontium peroxide nanomaterial or modified strontium peroxide nanomaterial and a special solvent for dispersion preparation; wherein the modified strontium peroxide nanomaterial is as described in any one of claims 10 to 12.

14. The product according to claim 13, characterized in that The preparation method of the strontium peroxide nanomaterial dispersion comprises: The ethanol dispersion of strontium peroxide nanomaterial or modified strontium peroxide nanomaterial is centrifuged to discard the supernatant, and then a special solvent for dispersion preparation is added to the precipitate and then ultrasonicated in a water bath to obtain a strontium peroxide nanomaterial dispersion preparation.

15. The product according to claim 14, characterized in that In the strontium peroxide nanomaterial dispersion, the concentration of the strontium peroxide nanomaterial or the modified strontium peroxide nanomaterial is 1 to 400 mM; and / or, in the ethanol dispersion, the concentration of the strontium peroxide nanomaterial or the modified strontium peroxide nanomaterial is 0.1 to 50 mg / mL; And / or, the special solvent for the dispersion preparation is at least one of short-chain polyethylene glycol and iodized oil; And / or, the centrifugation condition is 10000-15000 rpm for 8-20 minutes, and the water bath ultrasound time is 5-30 minutes.

16. Use of a strontium peroxide nanomaterial or a product obtained therefrom in the preparation of an anti-tumor drug, characterized in that: The strontium peroxide nanomaterial is as described in any one of claims 1 to 2 or is prepared by the preparation method described in any one of claims 3 to 7, and the product is as described in any one of claims 8 to 15.

17. The use according to claim 16, characterized in that The anti-tumor drug is a drug that can kill tumor cells, neutralize the acidic tumor microenvironment, alkalize tumor cells, and alleviate the hypoxic tumor microenvironment; and / or, The anti-tumor drug is a drug that regulates macrophage sugar metabolism to induce macrophage polarization to the anti-tumor M1 type and reshape the intratumor lactate metabolism crosstalk mode.

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