A hydrophilic Fe-Cu-Ni-S nanomaterial and its preparation method and application

Abstract

The present invention belongs to the technical field of nanomaterials, and specifically relates to a hydrophilic Fe‑Cu‑Ni‑S nanomaterial, a preparation method thereof, and an application thereof. The hydrophilic Fe‑Cu‑Ni‑S nanomaterial provided by the present invention comprises a Fe‑Cu‑Ni‑S nanomaterial and polyvinyl pyrrolidone modified on the surface of the Fe‑Cu‑Ni‑S nanomaterial; the Fe‑Cu‑Ni‑S nanomaterial is a sulfide formed by ferric ions, cuprous ions, nickel ions, and sulfide ions. The hydrophilic Fe‑Cu‑Ni‑S nanomaterial provided by the present invention is used as an integrated diagnosis and treatment probe for photoacoustic / nuclear magnetic resonance imaging and chemodynamic / photothermal / photodynamic therapy, and can obtain good photoacoustic / nuclear magnetic resonance imaging effects, as well as good tumor cell killing effects, while the organism does not experience weight loss, and toxic side effects on major organs such as the heart, liver, spleen, lungs, and kidneys.

Description

Technical Field

[0001] The invention belongs to the technical field of nanomaterials, and specifically relates to a hydrophilic Fe-Cu-Ni-S nanomaterial and a preparation method and application thereof. Background Art

[0002] Malignant tumors pose a serious threat to human life and health. According to statistics from the World Health Organization (WHO), in 2020, there were 19.29 million new patients with malignant tumors worldwide, and 10 million patients died of malignant tumors, which brought heavy economic burdens and mental stress to the people of the world. Therefore, effective diagnosis and treatment of malignant tumors is a major challenge facing the current biomedical research field. Surgical treatment, chemotherapy, radiotherapy and molecular targeted tumor therapy are the main treatment methods used in clinical practice. At the same time, with the rapid development of science and technology, new tumor diagnosis and treatment methods continue to emerge. Emerging treatment methods such as photothermal therapy, photodynamic therapy, chemodynamic therapy and molecular targeted immunotherapy are constantly being studied in depth and gradually entering clinical trials, opening another "window of God" for tumor treatment. In addition, the diagnostic and treatment technology that combines tumor diagnosis and treatment has received widespread attention in tumor treatment. It can realize real-time monitoring of the treatment effect, and then adjust the dosage or treatment plan in time, so as to achieve individualized drug administration for patients and improve the treatment effect.

[0003] At present, the integrated diagnosis and treatment materials that are being studied more mainly include integrated diagnosis and treatment nanomaterials with photothermal therapy, chemodynamic therapy or photodynamic therapy. Photothermal therapy refers to the use of materials with photothermal conversion to convert light energy into heat energy, thereby achieving local high temperature, and using the difference in temperature tolerance between normal tissue and tumor tissue to kill tumor cells without affecting normal tissue. Photodynamic therapy is a photosensitization reaction with biological effects that requires the participation of lasers, photosensitizers and oxygen molecules. The process is that laser irradiation of a specific wavelength excites the photosensitizers accumulated in the tumor tissue, and the excited photosensitizers transfer energy to the surrounding oxygen to generate highly reactive oxygen, destroying organelles such as mitochondria, lysosomes, and cell membranes in tumor cells, and further undergoing oxidation reactions with adjacent biological macromolecules to produce cytotoxic effects, which in turn lead to cell damage or even death. Therefore, it has the advantages of low toxic side effects, good efficacy, and high specificity. Chemodynamic therapy refers to the use of materials containing multivalent metal ions as catalysts for Fenton and Fenton-like reactions, catalyzing hydrogen peroxide to produce reactive oxygen species such as hydroxyl radicals, and high concentrations of hydroxyl radicals can oxidatively damage biomacromolecules such as lipids, proteins, and nucleic acids, thereby achieving the purpose of killing tumor cells. However, the currently developed integrated diagnosis and treatment probes still have various defects. For example, many integrated diagnosis and treatment probes are composed of a diagnostic method and a treatment method, the synthesis steps are complicated, and the doses required for diagnosis and treatment may not be consistent. Therefore, it is crucial to develop suitable integrated diagnosis and treatment nanomaterials. More interestingly, many researchers have tried synergistic treatment, that is, synthesizing a nanomaterial that has photothermal therapy, photodynamic therapy, and chemodynamic therapy effects at the same time, in order to overcome the defects of a single treatment method. The preparation conditions are complex and not conducive to mass production. At the same time, phototherapy methods need to rely on appropriate imaging technology to determine the distribution of phototherapy agents in the body and their enrichment in tumor tissues. Secondly, it is necessary to monitor the temperature changes of tumors and surrounding healthy tissues in real time during phototherapy. These are all major challenges faced by nanomaterials in the field of tumor treatment.

[0004] In summary, in order to further improve the efficiency of tumor diagnosis and treatment, it is necessary to develop nanomaterials with multimodal therapeutic effects mediated by multimodal imaging. Summary of the invention

[0005] The purpose of the present invention is to provide a hydrophilic Fe-Cu-Ni-S nanomaterial and a preparation method and application thereof. The hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention is used as an integrated diagnosis and treatment probe for photoacoustic / nuclear magnetic resonance imaging and chemodynamic / photothermal / photodynamic therapy, and can obtain good photoacoustic / nuclear magnetic resonance imaging effects and good tumor cell killing effects. At the same time, the organism does not experience weight loss, and toxic side effects on major organs such as the heart, liver, spleen, lungs, and kidneys.

[0006] The present invention provides a hydrophilic Fe-Cu-Ni-S nanomaterial, comprising a Fe-Cu-Ni-S nanomaterial and polyvinyl pyrrolidone modified on the surface of the Fe-Cu-Ni-S nanomaterial;

[0007] The Fe-Cu-Ni-S nanomaterial is a sulfide formed by trivalent iron ions, cuprous ions, divalent nickel ions and sulfur ions.

[0008] Preferably, the molar ratio of ferric ions, cuprous ions and divalent nickel ions in the Fe-Cu-Ni-S nanomaterial is 1:1:1.

[0009] Preferably, the particle size of the Fe-Cu-Ni-S nanomaterial is 5 to 10 nm.

[0010] Preferably, the preparation method of the Fe-Cu-Ni-S nanomaterial comprises the following steps:

[0011] Dissolving iron salt, nickel salt and cuprous salt in an organic amine solvent and heating to obtain a hot mixed metal salt solution;

[0012] dissolving sulfur powder in an organic amine solvent to obtain a sulfur precursor solution;

[0013] In a protective gas atmosphere, the sulfur precursor solution is injected into the hot mixed metal salt solution to carry out an in-situ reaction to obtain the Fe-Cu-Ni-S nanomaterial.

[0014] Preferably, during the injection, the temperature of the hot mixed metal salt solution is 260°C; the temperature of the sulfur precursor solution is 85°C;

[0015] The temperature of the in-situ reaction is 260° C., and the insulation time of the in-situ reaction is 5 minutes.

[0016] The present invention provides a method for preparing the hydrophilic Fe-Cu-Ni-S nanomaterial described in the above technical solution, comprising the following steps:

[0017] The Fe-Cu-Ni-S nanomaterial and polyvinyl pyrrolidone are surface-modified in an organic solvent to obtain the hydrophilic Fe-Cu-Ni-S nanomaterial.

[0018] The present invention provides the use of the hydrophilic Fe-Cu-Ni-S nanomaterial described in the above technical scheme or the hydrophilic Fe-Cu-Ni-S nanomaterial prepared by the preparation method described in the above technical scheme in the preparation of an integrated probe for tumor diagnosis and treatment.

[0019] Preferably, the tumor is a superficial solid tumor.

[0020] Preferably, the superficial solid tumor is a breast tumor and / or a melanoma tumor.

[0021] The present invention provides an integrated tumor diagnosis and treatment injection preparation, comprising the hydrophilic Fe-Cu-Ni-S nanomaterial described in the above technical solution or the hydrophilic Fe-Cu-Ni-S nanomaterial prepared by the preparation method described in the above technical solution and an injection solvent;

[0022] The injection solvent includes physiological saline or a pharmaceutically acceptable buffer.

[0023] The invention provides a hydrophilic Fe-Cu-Ni-S nano material, comprising the Fe-Cu-Ni-S nano material and polyvinyl pyrrolidone modified on the surface of the Fe-Cu-Ni-S nano material; the Fe-Cu-Ni-S nano material is a sulfide formed by trivalent ferrous ions, cuprous ions, divalent nickel ions and sulfide ions. The hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention comprises a Fe-Cu-Ni-S nanomaterial. On the one hand, the Fe-Cu-Ni-S nanomaterial has good ferromagnetism, can enhance the nuclear magnetic resonance signal of the part where the Fe-Cu-Ni-S nanomaterial is located, realize the nuclear magnetic resonance imaging of the part where the Fe-Cu-Ni-S nanomaterial is located, and thus realize the early nuclear magnetic diagnosis of the tumor; on the other hand, the Fe-Cu-Ni-S nanomaterial has a certain light absorption at 808nm near-infrared light, so that under the irradiation of near-infrared light, the photoacoustic signal of the irradiated part can be enhanced, and the photoacoustic imaging of the irradiated part can be realized. At the same time, under the irradiation of near-infrared light, the irradiated part is subjected to photothermal / photodynamic therapy, so as to inhibit the solid tumors of the primary lesion and the metastatic lesion, and achieve the effect of photothermal / photodynamic therapy. Finally, the hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention includes polyvinyl pyrrolidone modified on the surface of the Fe-Cu-Ni-S nanomaterial, and the surface layer of polyvinyl pyrrolidone can improve the hydrophilicity and safety of the Fe-Cu-Ni-S nanomaterial, and effectively avoid the cytotoxicity of the Fe-Cu-Ni-S nanomaterial. In summary, the hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention is used as an integrated diagnosis and treatment probe for photoacoustic / nuclear magnetic resonance imaging and chemodynamic / photothermal / photodynamic therapy, and can obtain good photoacoustic / nuclear magnetic resonance imaging effects, as well as good tumor cell killing effects, while the organism does not experience weight loss, and toxic side effects of major organs such as the heart, liver, spleen, lungs, and kidneys.

[0024] Furthermore, in the present invention, the preparation method of the Fe-Cu-Ni-S nanomaterial comprises the following steps: dissolving iron salt, nickel salt and cuprous salt in an organic amine solvent and heating to obtain a hot mixed metal salt solution; dissolving sulfur powder in an organic amine solvent to obtain a sulfur precursor solution; and injecting the sulfur precursor solution into the hot mixed metal salt solution in a protective gas atmosphere for in-situ reaction to obtain the Fe-Cu-Ni-S nanomaterial. The present invention synthesizes the Fe-Cu-Ni-S nanomaterial by a simple hot injection method, and the preparation method is simple and is conducive to mass production.

[0025] The present invention provides a method for preparing the hydrophilic Fe-Cu-Ni-S nanomaterial described in the above technical solution, comprising the following steps: surface-modifying the Fe-Cu-Ni-S nanomaterial and polyvinyl pyrrolidone (PVP) in an organic solvent to obtain the hydrophilic Fe-Cu-Ni-S nanomaterial. The present invention forms a hydrophilic Fe-Cu-Ni-S nanomaterial by modifying it with polyvinyl pyrrolidone in a solution, which not only improves the hydrophilicity of the Fe-Cu-Ni-S nanomaterial, but also reduces the toxicity of the Fe-Cu-Ni-S nanomaterial to organisms, and can provide photoacoustic imaging and nuclear magnetic resonance imaging effects for various tumor diagnoses. The preparation method provided by the present invention is simple and is conducive to mass production. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Product characterization diagram of the Fe-Cu-Ni-S nanomaterial and the hydrophilic Fe-Cu-Ni-S nanomaterial (denoted as PVP-Fe-Cu-Ni-S) prepared in Example 1 of the present invention; Figure 1 A in the figure is a transmission electron microscope image of Fe-Cu-Ni-S nanomaterial; Figure 1 B in the figure is the particle size distribution in the transmission electron microscope image; Figure 1 C in it is the element distribution map of the transmission electron microscope image of the prepared material Fe-Cu-Ni-S; Figure 1 D in it is the Zeta potential diagram of the prepared materials Fe-Cu-Ni-S and PVP-Fe-Cu-Ni-S;

[0027] Figure 2 This is a characterization diagram of the photothermal performance of the PVP-Fe-Cu-Ni-S nanomaterial prepared in Example 1 of the present invention; Figure 2 A in it is the UV-visible spectrum of PVP-Fe-Cu-Ni-S; Figure 2 B in the figure is the photothermal curve of PVP-Fe-Cu-Ni-S with different concentrations; Figure 2 Photothermal stability analysis chart of PVP-Fe-Cu-Ni-S with C of 1 mg / mL; Figure 2D in it is the photothermal conversion efficiency diagram of PVP-Fe-Cu-Ni-S;

[0028] Figure 3 This is a chemical kinetic performance characterization diagram of PVP-Fe-Cu-Ni-S prepared in Example 1 of the present invention; Figure 3 A in the figure is the absorbance result diagram of methylene blue color development reaction with different reaction time; Figure 3 B in the figure is the absorbance result diagram of the color development reaction of o-phenylenediamine at different time lengths; Figure 3 C in the figure is the absorbance result of ferrous ion detected by 2'2-bipyridine at 520nm; Figure 3 D in the figure is the result of different concentrations of PVP-Fe-Cu-Ni-S on the consumption of reduced glutathione and the colorimetric absorbance of dithiodinitrobenzoic acid;

[0029] Figure 4-1 to Figure 4-4 Photodynamic characterization diagram of PVP-Fe-Cu-Ni-S prepared in Example 1 of the present invention: Figure 4-1 A in the figure shows that different treatment groups catalyzed hydrogen peroxide to generate ROS in vitro, and the changes in absorbance at 420 nm were detected using the DPBF probe; Figure 4-1 B is the fluorescence result of intracellular ROS using DCFH-DA probe after 4T1 mouse breast cancer cells were treated with different methods; Figure 4-2 C in the figure is the flow cytometric count and statistical graph of intracellular ROS using the DCFH-DA probe after 4T1 mouse breast cancer cells were treated with different methods; Figure 4-3 D in the figure is the fluorescence result of singlet oxygen in 4T1 mouse breast cancer cells after different treatments using SOSG probe; Figure 4-4 E in the figure is the flow cytometric count and statistical graph of intracellular singlet oxygen using SOSG probe after 4T1 mouse breast cancer cells were treated with different methods;

[0030] Figure 5 This is a characterization graph of the cellular uptake ability of PVP-Fe-Cu-Ni-S prepared in Example 1 of the present invention; Figure 5 A in the figure is the flow cytometry chart of FITC-PVP-Fe-Cu-Ni-S uptake by cells in different treatment groups at different treatment times; Figure 5 B in the figure is the observation of the cell uptake of nanomaterials under transmission electron microscopy under the treatment of 0.2 mg / mL PVP-Fe-Cu-Ni-S;

[0031] Figure 6 The PVP-Fe-Cu-Ni-S prepared in Example 1 of the present invention was used for an in vivo treatment experiment on tumor-bearing mice; Figure 6A in the figure is the change of intratumor temperature over time after tumor-bearing mice were injected with PVP-Fe-Cu-Ni-S PBS dispersion and PBS solution and irradiated with near-infrared light; Figure 6 B in the figure is the change of tumor size in tumor-bearing mice after different treatments; Figure 6 C in the figure is the tumor volume record of different treatment groups after treatment; Figure 6 D in the figure is the weight record of mice in different treatment groups; Figure 6 E in the figure is an optical photograph of the in vitro tumors of mice after treatment in different treatment groups; Figure 6 F in the figure is the hematoxylin-eosin (HE) staining image of the tumor in different treatment groups one day after treatment. Figure 6 The scale bars in the figures in F are 100 μm;

[0032] Figure 7 This is an in vivo toxicity experiment of PVP-Fe-Cu-Ni-S prepared in Example 1 of the present invention; Figure 7 A and B in the figure are the toxicity experiments of PVP-Fe-Cu-Ni-S in vivo on day 7 and day 30, respectively, and are the hematoxylin-eosin (HE) staining images of the main organs. Figure 7 The scale bars in the figures are 100 μm;

[0033] Figure 8 This is a diagram showing the nuclear magnetic resonance imaging test results of PVP-Fe-Cu-Ni-S prepared in Example 1 of the present invention; Figure 8 A and C are the T1-weighted and T2-weighted images of magnetic resonance imaging of PVP-Fe-Cu-Ni-S prepared in agarose gel, respectively; Figure 8 B and D in the figure are respectively the vibration imaging T1-weighted and T2-weighted images in the tumor after intratumoral injection of PVP-Fe-Cu-Ni-S. DETAILED DESCRIPTION

[0034] The present invention provides a hydrophilic Fe-Cu-Ni-S nanomaterial, comprising a Fe-Cu-Ni-S nanomaterial and polyvinyl pyrrolidone modified on the surface of the Fe-Cu-Ni-S nanomaterial;

[0035] The Fe-Cu-Ni-S nanomaterial is a sulfide formed by ferric ions, cuprous ions, nickel ions and sulfide ions.

[0036] In the present invention, unless otherwise specified, all preparation raw materials / components are commercially available products well known to those skilled in the art.

[0037] In the present invention, the molar ratio of ferric ions, cuprous ions and divalent nickel ions in the Fe-Cu-Ni-S nanomaterial is preferably 1:1:1.

[0038] In the present invention, the particle size of the Fe-Cu-Ni-S nanomaterial is preferably 5 to 10 nm, more preferably 6 to 8 nm.

[0039] In the present invention, the preparation method of the Fe-Cu-Ni-S nanomaterial preferably comprises the following steps:

[0040] Dissolving iron salt, nickel salt and cuprous salt in an organic amine solvent and heating to obtain a hot mixed metal salt solution;

[0041] dissolving sulfur powder in an organic amine solvent to obtain a sulfur precursor solution;

[0042] In a protective gas atmosphere, the sulfur precursor solution is injected into the hot mixed metal salt solution to carry out an in-situ reaction to obtain the Fe-Cu-Ni-S nanomaterial.

[0043] The present invention dissolves iron salt, nickel salt and cuprous salt (hereinafter referred to as the first solution) in an organic amine solvent (hereinafter referred to as the first organic amine solvent) and heats the solution to obtain a hot mixed metal salt solution.

[0044] In the present invention, the iron salt is preferably ferric chloride. In a specific embodiment of the present invention, the iron salt is ferric chloride hexahydrate.

[0045] In the present invention, the nickel salt is preferably nickel chloride.

[0046] In the present invention, the cuprous salt is preferably cuprous chloride.

[0047] In the present invention, the first organic amine solvent is preferably oleylamine.

[0048] In a specific embodiment of the present invention, the molar ratio of the iron salt, the nickel salt and the cuprous salt is preferably 1:1:1.

[0049] In the present invention, the ratio of the total amount of the iron salt, the nickel salt and the cuprous salt to the volume of the first organic amine solvent is preferably 0.9 mmol:7 mL.

[0050] In the present invention, the heating temperature is preferably 260°C.

[0051] In the present invention, the dissolution is preferably performed under stirring conditions.

[0052] In the present invention, sulfur powder is dissolved (hereinafter referred to as the second solvent) in an organic amine solvent (hereinafter referred to as the second organic amine solvent) to obtain a sulfur precursor solution.

[0053] In the present invention, the second organic amine solvent is preferably oleylamine.

[0054] In the present invention, the ratio of the amount of the sulfur powder to the volume of the second organic amine solvent is preferably 1 mmol:3 mL.

[0055] In the present invention, the molar ratio of the iron salt to the sulfur powder is preferably 0.3:1.

[0056] In the present invention, the second dissolution is preferably performed under ultrasonic conditions.

[0057] After obtaining the mixed metal precursor solution and the sulfur precursor solution, the present invention injects the sulfur precursor solution into the hot mixed metal salt solution in a protective gas atmosphere for in-situ reaction to obtain the Fe-Cu-Ni-S nanomaterial.

[0058] In the present invention, before the injection, the present invention preferably heats the sulfur precursor solution. In the present invention, the heating temperature is preferably 85°C.

[0059] In the present invention, during the injection, the temperature of the hot mixed metal salt solution is preferably 260°C; the temperature of the sulfur precursor solution is preferably 85°C.

[0060] In the present invention, the temperature of the in-situ reaction is preferably 260° C., and the holding time of the in-situ reaction is preferably 5 min. In the present invention, the in-situ reaction is preferably carried out under stirring, and the stirring is preferably magnetic stirring.

[0061] In the present invention, the protective gas is preferably nitrogen or an inert gas, and the inert gas is preferably argon.

[0062] In the present invention, the in-situ reaction obtains an in-situ reaction liquid. The present invention preferably performs post-treatment on the reaction liquid to obtain the Fe-Cu-Ni-S nanomaterial. In the present invention, the post-treatment preferably comprises the following steps: cooling the in-situ reaction liquid to room temperature and then performing solid-liquid separation to obtain a solid phase product; washing and drying the solid phase product in sequence to obtain the Fe-Cu-Ni-S nanomaterial. In the present invention, the solid-liquid separation is preferably centrifugal separation. In the present invention, the washing is preferably: washing with methanol and chloroform in sequence for multiple times. In the present invention, the drying is preferably vacuum drying, the temperature of the vacuum drying is preferably 60°C, and the insulation time of the vacuum drying is preferably 2h.

[0063] The present invention provides a method for preparing the hydrophilic Fe-Cu-Ni-S nanomaterial described in the above technical solution, comprising the following steps:

[0064] The Fe-Cu-Ni-S nanomaterial and polyvinyl pyrrolidone are surface-modified in an organic solvent to obtain the hydrophilic Fe-Cu-Ni-S nanomaterial.

[0065] In the present invention, the organic solvent is preferably anhydrous ethanol or chloroform.

[0066] In the present invention, the mass ratio of the Fe-Cu-Ni-S nanomaterial to polyvinyl pyrrolidone is preferably 1:5.

[0067] In the present invention, the step of mixing the Fe-Cu-Ni-S nanomaterial, polyvinyl pyrrolidone and the organic solvent is preferably: dissolving the Fe-Cu-Ni-S nanomaterial in the organic solvent to obtain a Fe-Cu-Ni-S nanomaterial solution; and mixing the Fe-Cu-Ni-S nanomaterial solution and the polyvinyl pyrrolidone.

[0068] In the present invention, the surface modification is preferably carried out at room temperature, the surface modification time is preferably 24 hours, and the surface modification is preferably carried out under stirring conditions, and the stirring is preferably magnetic stirring.

[0069] In the present invention, during the surface modification, the polyvinyl pyrrolidone is physically modified on the surface of the iron-nickel composite sulfide to form a protective layer. In the present invention, the physical modification means that the polyvinyl pyrrolidone is physically coated on the surface of the Fe-Cu-Ni-S nanomaterial.

[0070] In the present invention, after the surface modification, a surface modification reaction liquid is obtained. In the present invention, the surface modification reaction liquid is preferably post-treated to obtain the hydrophilic Fe-Cu-Ni-S nanomaterial. In the present invention, the post-treatment preferably includes the following steps: removing the organic solvent in the surface modification reaction liquid to obtain a solid product; washing and drying the solid product in sequence to obtain the hydrophilic Fe-Cu-Ni-S nanomaterial. In the present invention, the specific implementation method of removing the organic solvent is preferably heating evaporation, and the temperature of the heating evaporation is preferably 55°C. The washing is preferably performed with deionized water, and the number of washings is preferably 3 times. In the present invention, the drying is preferably vacuum drying, and the temperature of the vacuum drying is preferably 80°C.

[0071] The present invention provides the use of the hydrophilic Fe-Cu-Ni-S nanomaterial described in the above technical scheme or the hydrophilic Fe-Cu-Ni-S nanomaterial prepared by the preparation method described in the above technical scheme in the preparation of an integrated probe for tumor diagnosis and treatment.

[0072] Preferably, the tumor is a superficial solid tumor.

[0073] Preferably, the superficial solid tumor is a breast tumor and / or a melanoma tumor.

[0074] When the hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention is used to prepare an integrated tumor diagnosis and treatment probe, the amount of the hydrophilic Fe-Cu-Ni-S nanomaterial is preferably determined according to the requirements of biological imaging; the amount used for chemodynamic / photothermal / photodynamic therapy is preferably determined according to the number of tumor cells to be treated and the disease stage of the tumor-stricken organism.

[0075] In the present invention, when used, the hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention is preferably administered to a living body by intravenous injection or intratumoral injection to perform biological imaging or treat tumors.

[0076] The present invention provides an integrated tumor diagnosis and treatment injection preparation, comprising the hydrophilic Fe-Cu-Ni-S nanomaterial described in the above technical solution or the hydrophilic Fe-Cu-Ni-S nanomaterial prepared by the preparation method described in the above technical solution and an injection solvent;

[0077] The injection solvent includes physiological saline or a pharmaceutically acceptable buffer.

[0078] In the present invention, the physiological saline is preferably a sodium chloride solution with a mass percentage of preferably 0.9%.

[0079] In the present invention, the pharmaceutically acceptable buffer is preferably a PBS buffer having a pH value of 7 to 9.

[0080] In the present invention, the integrated tumor diagnosis and treatment injection preparation preferably also includes pharmaceutically acceptable excipients.

[0081] In the present invention, the pharmaceutically acceptable excipients preferably include one or more of glucose, glycerol, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, oxyethylene sorbitan fatty acid ester, analgesics and stabilizers.

[0082] The hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention is used as a nanoprobe, and the amount used for biological imaging can be determined according to the imaging requirements; the amount used for chemodynamic / photothermal / photodynamic therapy can be determined according to the number of tumor cells to be treated and the disease stage of the tumor-stricken organism.

[0083] The hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention can be used as a nanoprobe and administered to an organism by intravenous injection, intratumoral injection, etc., to perform biological imaging or treat tumors.

[0084] When the hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention is used in the preparation of an integrated tumor diagnosis and treatment probe, the integrated tumor diagnosis and treatment probe is a probe material for photoacoustic / nuclear magnetic resonance imaging and chemodynamic / photothermal / photodynamic therapy. The hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention can obtain good photoacoustic / nuclear magnetic resonance imaging effects and good tumor cell killing effects, while the organism does not experience weight loss and toxic side effects on major organs such as the heart, liver, spleen, lungs, and kidneys.

[0085] Compared with existing nanomaterials with multiple therapeutic effects, the hydrophilic Fe-Cu-Ni-S nanomaterial provided by the present invention has a simple preparation method, low cost and significant effect, and provides a new idea for the preparation of nanomaterials for tumor treatment.

[0086] In order to further illustrate the present invention, the technical solution provided by the present invention is described in detail below in conjunction with the accompanying drawings and embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0087] Example 1

[0088] 1) Dissolve 0.3 mmol of ferric chloride hexahydrate, 0.3 mmol of nickel chloride and 0.3 mmol of cuprous chloride in 7 mL of oleylamine, stir magnetically and heat to 260° C. in a 50 mL three-necked flask to obtain a mixed metal precursor solution;

[0089] 2) Dissolve 1 mmol of sulfur powder in 3 mL of oleylamine, sonicate to fully dissolve it, and heat it to 85° C. to obtain a sulfur precursor solution;

[0090] 3) When the temperature of the mixed metal precursor solution reaches 260°C, the 85°C sulfur precursor solution in step 2) is injected into the mixed metal precursor solution in step 1) in a nitrogen atmosphere, and magnetic stirring is continued for 5 minutes. When the reaction is completed, it is naturally cooled to room temperature, and the reaction solution is transferred to a centrifuge tube. The solid material is repeatedly washed with methanol and chloroform, and vacuum dried at 60°C for 2h to obtain Fe-Cu-Ni-S nanomaterials;

[0091] 4) Weigh 10 mg of the Fe-Cu-Ni-S nanomaterial obtained in step 3) and dissolve it in 10 mL of chloroform, stir it magnetically, and add 50 mg of polyvinylpyrrolidone (PVP) at the same time, and continue stirring at room temperature in a fume hood for 24 hours;

[0092] 5) heating the mixed system of step 4) to 55° C. until the chloroform is completely evaporated;

[0093] 6) Wash the product obtained in step 5) with water three times and dry it in a vacuum drying oven at 80° C. The product is a hydrophilic Fe-Cu-Ni-S nanomaterial, recorded as PVP-Fe-Cu-Ni-S material.

[0094] Test Example 1

[0095] Figure 1 Product characterization diagram of the Fe-Cu-Ni-S nanomaterial and the hydrophilic Fe-Cu-Ni-S nanomaterial (denoted as PVP-Fe-Cu-Ni-S) prepared in Example 1 of the present invention; Figure 1 A in the figure is a transmission electron microscope image of Fe-Cu-Ni-S nanomaterial; Figure 1 B in the figure is the particle size distribution in the transmission electron microscope image; Figure 1 C is the element distribution map of the transmission electron microscope image of the prepared material Fe-Cu-Ni-S; Figure 1 D in the figure is the Zeta potential diagram of the prepared materials Fe-Cu-Ni-S and PVP-Fe-Cu-Ni-S.

[0096] Depend on Figure 1 It can be seen from A and B in that the Fe-Cu-Ni-S nanomaterial prepared in Example 1 is spherical particles of 5 to 10 nm.

[0097] Depend on Figure 1 It can be seen from the C in that the Fe-Cu-Ni-S nanomaterial prepared in Example 1 contains four elements: Fe, Cu, Ni, and S.

[0098] Depend on Figure 1 From D, we can see that the surface of the Fe-Cu-Ni-S ultrasmall nanomaterial has a negative charge of -38mV. After being wrapped by the PVP material, the negative charge on the surface of PVP-Fe-Cu-Ni-S is reduced to -15mV, indicating that the Fe-Cu-Ni-S ultrasmall nanomaterial is indeed wrapped with PVP, indicating the successful synthesis of PVP-Fe-Cu-Ni-S.

[0099] Test Example 2

[0100] Characterization of photothermal properties of PVP-Fe-Cu-Ni-S ultra-small nanomaterials:

[0101] Weigh 10 mg of the PVP-Fe-Cu-Ni-S material prepared in Example 1, add 1 mL of ultrapure water to prepare a 10 mg / mL dispersion mother solution, then dilute it into 0.1, 0.25, 0.5 and 1 mg / mL dispersions, and scan the UV-visible light spectroscopic absorbance of the diluted PVP-Fe-Cu-Ni-S dispersions (prepared with ultrapure water). The results are as follows: Figure 2 A in.

[0102] The 10 mg / mL PVP-Fe-Cu-Ni-S dispersion was diluted to 0.1, 0.5, 1, and 2 mg / mL dispersions. The dispersions of different concentrations were placed under a laser with a wavelength of 808 nm (Shanghai Xilong Optoelectronics Technology Co., Ltd.) at 1 W / cm 2 The power was irradiated for 10 minutes, and the temperature changes over time were recorded with a thermal imager. Water was used as the control group. The results are shown in Figure 2 B in.

[0103] A 1 mg / mL PVP-Fe-Cu-Ni-S dispersion (prepared in ultrapure water) was irradiated with a laser at a wavelength of 808 nm at 1 W / cm 2 The power was irradiated for 10 minutes, and then stopped for 10 minutes and then continued to irradiate for three heating / cooling cycles. The temperature change monitoring results were as follows: Figure 2 C in.

[0104] A 1 mg / mL PVP-Fe-Cu-Ni-S dispersion (prepared in ultrapure water) was irradiated with a laser at a wavelength of 808 nm at 1 W / cm 2 The power was irradiated for 10 minutes, and then irradiated again after stopping for 10 minutes. The cooling curve was taken and the photothermal conversion efficiency of the PVP-Fe-Cu-Ni-S ultra-small nanomaterial was calculated in combination with parameters such as absorbance. The results are as follows Figure 2 D in.

[0105] Depend on Figure 2 It can be seen from A in that the UV-visible spectrum absorbance of PVP-Fe-Cu-Ni-S increases with the increase of concentration.

[0106] Depend on Figure 2 It can be seen from B that under the same light density conditions (1W / cm 2 ), as the concentration of PVP-Fe-Cu-Ni-S dispersion increased, the temperature gradually increased, while the water in the control group had almost no warming effect, which proved that PVP-Fe-Cu-Ni-S had a good photothermal effect and was concentration-dependent.

[0107] Depend on Figure 2 It can be seen from C in that in the three heating / cooling cycles, the PVP-Fe-Cu-Ni-S dispersion shows stable heating performance.

[0108] Depend on Figure 2 As shown in D, before and after the heating / cooling cycle, PVP-Fe-Cu-Ni-S showed an excellent photothermal conversion efficiency of 96%.

[0109] Test Example 3

[0110] Chemical kinetics performance characterization of PVP-Fe-Cu-Ni-S materials:

[0111] Prepare a PVP-Fe-Cu-Ni-S dispersion (prepared with ultrapure water) with a mother solution concentration of 10 mg / mL, add 200 μL to 1 mL of a methylene blue reaction system (methylene blue 20 μg / mL, hydrogen peroxide 100 μM), centrifuge at 10000 rpm for 5 minutes after reacting for different lengths of time, and perform UV-visible spectral absorbance detection on the supernatant solution. The results are as follows Figure 3 A in the figure and the characteristic absorption peak at 665nm were used for data statistics.

[0112] Prepare a PVP-Fe-Cu-Ni-S dispersion (prepared with ultrapure water) with a mother solution concentration of 10 mg / mL, add 200 μL to 1 mL of o-phenylenediamine reaction system (o-phenylenediamine 10 mM, hydrogen peroxide 100 μM), centrifuge at 10000 rpm for 5 minutes after reacting for different lengths of time, and perform UV-visible spectral absorbance detection on the supernatant solution. The results are as follows Figure 3 B in the figure, and the characteristic absorption peak at 452nm was used for data statistics.

[0113] Prepare a PVP-Fe-Cu-Ni-S dispersion (prepared with ultrapure water) with a mother solution concentration of 10 mg / mL, take 200 μL and add it to 1 mL of 2'2-bipyridine reaction system (2'2-bipyridine 6 mM, pH = 5 / 6 / 7.4), while the positive control group is FeSO4 added to the system. After 24 hours of reaction, centrifuge at 10000 rpm for 5 minutes, and perform UV-visible spectral absorbance detection on the supernatant solution. The results are as follows Figure 3 C in the sample and the characteristic absorption peak at 520 nm were used for data statistics.

[0114] Prepare a PVP-Fe-Cu-Ni-S dispersion (prepared with ultrapure water) with a mother solution concentration of 10 mg / mL, add 0, 25, 50, 100 and 200 μL to 1 mL of glutathione reaction system (glutathione 10 mM, dithiodinitrobenzoic acid 0.1 mM) to make the final concentration of PVP-Fe-Cu-Ni-S in the system 0, 0.025, 0.05, 0.1 and 0.2 mg / mL, react for different time periods of 1, 12 and 24 h, centrifuge at 10000 rpm for 5 minutes, and perform UV-visible spectral absorbance detection on the supernatant solution. Figure 3 The D in the figure is used, and the characteristic absorption peak at 412 nm is used for data statistics.

[0115] Depend on Figure 3It can be seen from A in that: under the same concentration of PVP-Fe-Cu-Ni-S, the longer the reaction time, the lower the absorbance of the methylene blue reaction system at 665nm, which proves that hydroxyl radicals are continuously generated in the system.

[0116] Depend on Figure 3 From B in Figure 1, we can see that under the same concentration of PVP-Fe-Cu-Ni-S, the longer the reaction time, the greater the absorbance of the o-phenylenediamine reaction system at 450nm, proving that hydroxyl radicals are continuously generated in the system.

[0117] Depend on Figure 3 It can be seen from C that: under the same concentration of PVP-Fe-Cu-Ni-S, in the reaction solution with a pH of 5, the absorbance at 520nm increased significantly, proving the presence of divalent iron ions.

[0118] Depend on Figure 3 It can be seen from D that in the case of gradient concentrations of PVP-Fe-Cu-Ni-S, the higher the concentration, the lower the absorbance of the glutathione reaction system at 412nm. This proves that PVP-Fe-Cu-Ni-S can degrade glutathione, and the degradation is greater with the extension of time.

[0119] Test Example 4

[0120] PVP-Fe-Cu-Ni-S produces ROS effect:

[0121] 1 mL of PVP-Fe-Cu-Ni-S (0.2 mg / mL pure water dispersion) was added to 1,3-diphenylisobenzofuran (DPBF) and the 808 nm (1 W / cm 2 ) near-infrared light for 0, 1, 2, 3, 4, 5, and 10 minutes, then the solution was centrifuged at 10000 rpm for 5 minutes, and the supernatant was subjected to absorbance detection by UV-visible absorption spectrum. The results are shown in Figure 4-1 A in

[0122] 4T1 breast cancer cells were cultured in 96-well plates with DMEM + 10% FBS medium until the density was close to 70%. Then, 10 mg / mL PVP-Fe-Cu-Ni-S PBS dispersion stock solution was prepared in DMEM culture medium until the concentration gradient was 0, 0.05, 0.1, and 0.2 mg / mL. When changing the medium, it was added to the PVP-Fe-Cu-Ni-S group and the PVP-Fe-Cu-Ni-S + irradiation group and incubated for 24 hours. Then, the irradiation group and the PVP-Fe-Cu-Ni-S + irradiation group were exposed to 808 nm (1 W / cm 2) near-infrared light for 5 minutes. Subsequently, each group was incubated with DCFH-DA probe (10 μM) and singlet oxygen (SingletOxygen SensorGreen, SOSG) probe for 30 minutes, washed three times with serum-free DMEM medium, and covered with 20 μL DPBS, and then observed and photographed under a fluorescence microscope. The results are shown in B and Figure 4-3 D in.

[0123] 4T1 breast cancer cells were cultured in DMEM + 10% FBS medium in a 6-well plate until the density was close to 70%. Then, 10 mg / mL PVP-Fe-Cu-Ni-S PBS dispersion stock solution was prepared in DMEM culture medium to a concentration gradient of 0, 0.05, 0.1, and 0.2 mg / mL. When changing the medium, it was added to the PVP-Fe-Cu-Ni-S group and the PVP-Fe-Cu-Ni-S + irradiation group and incubated for 24 hours. Then, the irradiation group and the PVP-Fe-Cu-Ni-S + irradiation group were exposed to 808 nm (1 W / cm 2 ) near-infrared light for 5 minutes. Subsequently, each group was incubated with DCFH-DA probe (10 μM) and singlet oxygen (SingletOxygen SensorGreen, SOSG) probe for 30 minutes, washed three times with serum-free DMEM medium, and covered with 20 μL DPBS. The cells were counted and the differences were statistically analyzed using a flow cytometer. The results are shown in Figure 4-2 C and Figure 4-4 E in.

[0124] Depend on Figure 4-1 As can be seen from A in the figure, the PVP-Fe-Cu-Ni-S+ irradiation group showed a stronger fluorescence intensity, proving that it has the effect of photodynamically producing ROS.

[0125] Depend on Figure 4-1 to Figure 4-4 From B, C, D, and E in the figure, we can see that Figure 4-1 Corresponding to the results of A in the figure, PVP-Fe-Cu-Ni-S promoted the production of ROS / SOSG in 4T1 cells after co-incubation with 4T1 cells; while PVP-Fe-Cu-Ni-S+irradiation treatment promoted the production of more ROS / SOSG in 4T1 cells, indicating that PVP-Fe-Cu-Ni-S has a strong photodynamic effect under light triggering.

[0126] Test Example 5

[0127] Characterization of cellular uptake ability of PVP-Fe-Cu-Ni-S:

[0128] The PVP-Fe-Cu-Ni-S nanomaterial and 100 μL FITC (1 mg / mL) were mixed and stirred for 24 h, collected by centrifugation and redivided to 10 mg / mL, and named FITC-PVP-Fe-Cu-Ni-S.

[0129] 4T1 breast cancer cells were cultured in 6-well plates with DMEM + 10% FBS medium. When the density was close to 70%, 10 mg / mL FITC-PVP-Fe-Cu-Ni-S PBS dispersion stock solution was prepared in DMEM culture medium to a concentration gradient of 0, 0.05, 0.1, and 0.2 mg / mL. When changing the medium, it was added to the FITC-PVP-Fe-Cu-Ni-S group and incubated for 1, 2, 4, 8, 12, and 24 hours. The cells were then collected, counted and statistically analyzed under a flow cytometer. The results are shown in Figure 5 A in.

[0130] 4T1 breast cancer cells were cultured in DMEM + 10% FBS medium in a 6-well plate. When the density was close to 70%, 0.2 mg / mL PVP-Fe-Cu-Ni-S was incubated with the cells for 1 hour. The cells were then collected, fixed with glutaraldehyde, stained, and the uptake of PVP-Fe-Cu-Ni-S by cells was observed using a transmission electron microscope. The results are shown in the figure. Figure 5 B in.

[0131] Depend on Figure 5 As shown in A, FITC-PVP-Fe-Cu-Ni-S can be rapidly taken up by cells and has a certain concentration gradient dependence.

[0132] Depend on Figure 5 As shown in Figure B, it was indeed observed under a transmission electron microscope that cells engulfed PVP-Fe-Cu-Ni-S.

[0133] Test Example 6

[0134] PVP-Fe-Cu-Ni-S is used in in vivo therapeutic experiments in tumor-bearing mice:

[0135] PVP-Fe-Cu-Ni-S is hereinafter referred to as PVP-NPs. 4T1 breast cancer cells (purchased from ATCC) were cultured in DMEM + 10% FBS medium. After culture and passage, each mouse was injected with 10 6 4T1 breast cancer cells were used to establish a subcutaneous tumor-bearing model in BALB / c mice. 3 The tumor-bearing mice were randomly divided into four groups:

[0136] (1) Control group, which was injected with PBS buffer solution only and not irradiated with near-infrared light;

[0137] (2) PBS+irradiation group, injected with PBS buffer and subjected to near-infrared irradiation;

[0138] (3) PVP-NPs group, only injected with material without NIR light irradiation;

[0139] (4) PVP-NPs + irradiation group, injected with material and subjected to near-infrared irradiation;

[0140] Each group had 10 mice. PVP-NPs dispersion and PBS were administered by intratumoral injection. PVP-NPs dispersion was prepared with 1×PBS buffer to a concentration of 2 mg / mL, and the amount injected into the mouse tumor was 50 μL. After the intratumoral injection, the tumor sites of mice in groups (2) and (4) were exposed to 808 nm (1 W / cm 2 ) Near infrared light was irradiated for 10 minutes, and the temperature changes during the process were recorded by a thermal imaging camera. The results are as follows Figure 6 A in.

[0141] After treatment, take pictures and record the size of the mouse tumor and the weight of the mouse every two days until the 15th day (the day of treatment is day 0). After 15 days, the tumor is removed and photographed. The results are as follows: Figure 6 B, C, D and E in.

[0142] One day after treatment, 5 mice in each group were killed, the tumors were removed and sections were made, and the results of hematoxylin-eosin staining were as follows: Figure 6 F in.

[0143] Depend on Figure 6 As shown in A, after the injection of PVP-NPs and the start of near-infrared light irradiation, the temperature rose rapidly and reached nearly 60°C within 2 minutes. Compared with the group injected with PBS only, there was only a slight temperature increase, which proves that PVP-NPs have a good warming effect in vivo.

[0144] Depend on Figure 6 From B and C, we can see that after treatment, the tumor volume of mice in the PVP-NPs+irradiation group showed no growth trend and gradually decreased, while the tumor volumes of other groups gradually increased. On the 15th day, there was a significant difference in tumor volume between the PVP-NPs+irradiation group and the other three groups, proving that PVP-NPs+irradiation therapy can effectively inhibit tumor growth.

[0145] Depend on Figure 6 From D, we can see that there was no significant difference in the body weight of mice in each treatment group within the 15-day record, which proves that PVP-NPs material has no obvious toxic side effects in the treatment of mice.

[0146] Depend on Figure 6As shown in E, the tumor in the PVP-NPs+irradiation group became smaller or even disappeared, which was significantly different from the other three groups, indicating that it can effectively inhibit tumor growth.

[0147] Depend on Figure 6 As shown in F, the section staining results of the PVP-NPs+irradiation group showed large areas of cell necrosis in the tumor, proving that PVP-NPs+irradiation can effectively kill the tumor.

[0148] The above data show that PVP-NPs material has a significant effect in treating tumors in combination with near-infrared light.

[0149] Test Example 7

[0150] In vivo toxicity test of PVP-Fe-Cu-Ni-S:

[0151] Each group had 10 mice, divided into a control group and a PVP-NPs group. The control group was injected with 100 μL of PBS through the tail vein, while the PVP-NPs group was injected with 100 μL of PVP-NPs PBS dispersion (10 mg / mL). At day 7 and 30, 5 mice were killed in the control group and the PVP-NPs group, and the main internal organs of the heart, liver, spleen, lung and kidney were collected. Figure 7 A and B in.

[0152] Depend on Figure 7 It can be seen that there was no obvious pathological damage to major organs such as the heart, liver, spleen, lungs, and kidneys on days 7 and 30, indicating that the obtained PVP-NPs have no toxic side effects on organisms, further demonstrating its safety and reliability.

[0153] Test Case 8

[0154] PVP-Fe-Cu-Ni-S MRI test results:

[0155] In the in vitro imaging experiment, PVP-Fe-Cu-Ni-S was used to prepare a series of test tubes with concentration gradients in agarose gel, and the results were as follows: Figure 8 A and C in the figure; the in vivo T1- and T2-weighted imaging of the intratumoral injection showed the following results: Figure 8 B and D in Figure 8 A and C show that PVP-Fe-Cu-Ni-S has good T1- and T2-weighted MRI capabilities and is concentration-dependent; the higher the concentration, the stronger the signal.

[0156] Depend on Figure 8 From B and D in the figure, we can see that PVP-Fe-Cu-Ni-S has good in vivo nuclear magnetic resonance imaging effect.

[0157] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A hydrophilic Fe-Cu-Ni-S nanomaterial, It is characterized in that It comprises a Fe-Cu-Ni-S nano material and polyvinyl pyrrolidone modified on the surface of the Fe-Cu-Ni-S nano material; The Fe-Cu-Ni-S nanomaterial is a sulfide formed by trivalent iron ions, cuprous ions, divalent nickel ions and sulfur ions; The molar ratio of ferric ions, cuprous ions and divalent nickel ions in the Fe-Cu-Ni-S nanomaterial is 1:1:1; The preparation method of the Fe-Cu-Ni-S nanomaterial comprises the following steps: Dissolving iron salt, nickel salt and cuprous salt in oleylamine and heating to obtain a hot mixed metal salt solution; dissolving sulfur powder in oleylamine to obtain a sulfur precursor solution; In a protective gas atmosphere, injecting the sulfur precursor solution into the hot mixed metal salt solution for in-situ reaction, wherein the temperature of the hot mixed metal salt solution is 260° C. and the temperature of the sulfur precursor solution is 85° C., to obtain the Fe-Cu-Ni-S nanomaterial; The preparation method of the hydrophilic Fe-Cu-Ni-S nanomaterial comprises the following steps: The Fe-Cu-Ni-S nanomaterial and polyvinyl pyrrolidone are surface-modified in an organic solvent to obtain the hydrophilic Fe-Cu-Ni-S nanomaterial.

2. The hydrophilic Fe-Cu-Ni-S nanomaterial according to claim 1, It is characterized in that The particle size of the Fe-Cu-Ni-S nano material is 5-10 nm.

3. The hydrophilic Fe-Cu-Ni-S nanomaterial according to claim 1, It is characterized in that The temperature of the in-situ reaction is 260° C., and the insulation time of the in-situ reaction is 5 minutes.

4. The method for preparing the hydrophilic Fe-Cu-Ni-S nanomaterial according to any one of claims 1 to 3, It is characterized in that The following steps are involved: The Fe-Cu-Ni-S nanomaterial and polyvinyl pyrrolidone are surface-modified in an organic solvent to obtain the hydrophilic Fe-Cu-Ni-S nanomaterial.

5. Use of the hydrophilic Fe-Cu-Ni-S nanomaterial according to any one of claims 1 to 3 or the hydrophilic Fe-Cu-Ni-S nanomaterial prepared by the preparation method according to claim 4 in the preparation of an integrated probe for tumor diagnosis and treatment.

6. The use according to claim 5, It is characterized in that The tumor is a superficial solid tumor.

7. The use according to claim 6, It is characterized in that The superficial solid tumor is a breast tumor and / or a melanoma tumor.

8. An integrated injection preparation for tumor diagnosis and treatment, It is characterized in that The invention comprises the hydrophilic Fe-Cu-Ni-S nanomaterial according to any one of claims 1 to 3 or the hydrophilic Fe-Cu-Ni-S nanomaterial prepared by the preparation method according to claim 4 and an injection solvent; The injection solvent includes physiological saline or a pharmaceutically acceptable buffer.

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