Preparation method and application of gold-platinum-iron flower-shaped nano composite material with cascade catalytic capability

Abstract

The invention discloses a preparation method and application of a gold-platinum-iron flower-shaped nano composite material with cascade catalytic capacity, and relates to the technical field of tumor hunger therapy, chemical power therapy and near-infrared photothermal therapy. According to the preparation method of the gold-platinum-iron flower-shaped nano composite material with the cascade catalytic capability, the flower-shaped zeolite imidazole framework is further modified and pyrolyzed, and the iron element is anchored on the carbon framework in a monatomic state; gold-platinum nanoparticles and hyaluronic acid which are tightly combined and grow in situ are further loaded on the surface of the nano-material, so that the nano-material has good biocompatibility and targeting property and can be used as a nano-composite material for tumor chemotherapy and near-infrared photothermal therapy. According to the invention, the variety of nano composite materials for tumor targeted hunger therapy, chemotherapy and near-infrared photothermal therapy by taking a zeolite-like imidazole skeleton as a substrate is enriched. The invention can obtain the preparation method and application of the gold-platinum-iron flower-shaped nano composite material with the cascade catalytic capability.

Description

Technical Field

[0001] The present invention relates to the technical fields of tumor starvation therapy, chemodynamic therapy and near-infrared photothermal therapy, and particularly relates to a preparation method and application of a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability. Background Art

[0002] In recent years, the incidence of tumors has been increasing year by year, and the mortality rate remains high, which is a major disease threatening public health. At the same time, the current tumor surgical resection, radiotherapy and chemotherapy methods lack targeting, and the sensitivity and specificity are not high. Therefore, exploring a nanomaterial that combines diagnosis and treatment, is efficient and safe, and formulating a more individualized and precise diagnosis and treatment plan for tumor patients is a current research hotspot in tumor treatment and also has broad clinical application prospects.

[0003] Chemotherapy (CDT) utilizes the unique biochemical characteristics in the tumor microenvironment, and uses nanomaterials as catalysts to initiate in-situ chemical reactions in the tumor region to generate a large amount of ROS to kill tumor cells. Near-infrared light can penetrate skin, tissues, blood, etc. well, and is an ideal choice for a non-invasive light source treatment platform for tumor treatment. Under traditional light irradiation, photothermal therapy (PTT) converts light energy into heat energy to kill tumor cells.

[0004] Inorganic metal nanomaterials have been proven to exhibit various types of enzyme activities, such as peroxidase-like activity, catalase-like activity, glucose oxidase-like activity, etc. However, a single material often only exhibits one or two dominant activities. When these inorganic metal nanomaterials are used for tumor treatment, there are problems such as single activity and insufficient targeting. Therefore, there is an urgent need to develop a new type of nanomaterial that can target tumors and has multiple enzyme activities to solve the above problems. Summary of the Invention

[0005] The purpose of the present invention is to solve the above technical problems, and provide a preparation method and application of a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability.

[0006] A preparation method of a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability is carried out according to the following steps:

[0007] Step S1, synthesis of flower-like zeolitic imidazolate frameworks:

[0008] Using dopamine hydrochloride, zinc nitrate hexahydrate and 2-methylimidazole as raw materials for synthesis to obtain a flower-like zeolitic imidazolate framework material;

[0009] Step S2, the first high-temperature pyrolysis:

[0010] The flower-like zeolitic imidazolate framework material obtained in step S1 is subjected to the first high-temperature pyrolysis under a nitrogen atmosphere to obtain the flower-like zeolitic imidazolate framework material after the first pyrolysis;

[0011] Step S3, the second high-temperature pyrolysis:

[0012] The flower-like zeolitic imidazolate framework material after the first pyrolysis obtained in step S2 is subjected to the second high-temperature pyrolysis with ferrous sulfate and 2,2'-bipyridine under a nitrogen atmosphere to obtain a flower-like iron single-atom nanomaterial;

[0013] Step S4, loading gold-platinum nanoparticles:

[0014] The flower-like iron single-atom nanomaterial obtained in step S3 is mixed with chloroauric acid solution and chloroplatinic acid solution, and then reduced using a reducing agent to obtain a gold-platinum-iron flower-like nanomaterial;

[0015] Step S5, hyaluronic acid modification:

[0016] The gold-platinum-iron flower-like nanomaterial obtained in step S4 is modified with hyaluronic acid to obtain a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability.

[0017] Application of a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability, and application of the gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability in the preparation of tumor diagnostic materials, tumor-targeted chemotherapeutic starvation therapy drugs, and near-infrared photothermal synergistic photodynamic therapy drugs.

[0018] Advantages of the present invention:

[0019] The preparation method of the gold-platinum-iron flower-like nanocomposite material of the present invention further modifies and pyrolyzes on the flower-like zeolitic imidazolate framework, anchors iron elements in a single-atom state to the carbon framework, and further loads tightly bound and in-situ grown gold-platinum nanoparticles and hyaluronic acid on its surface, making it have good biocompatibility and targeting, and can be used as a nanocomposite material for tumor chemotherapy and near-infrared photothermal therapy. The present invention enriches the types of nanocomposite materials for tumor-targeted starvation therapy, chemotherapy, and near-infrared photothermal therapy based on zeolitic imidazolate frameworks.

[0020] Due to the glucose oxidase-like activity (GOx) of gold-platinum nanoparticles, they can consume glucose within tumor cells under aerobic conditions and cut off the energy source of tumor cells. Moreover, since gold and platinum have relatively high atomic numbers, they possess excellent X-ray attenuation properties, and gold nanoparticles have a high near-infrared light absorption rate. Therefore, gold nanoparticles are expected to become qualified contrast agents for tumor computed tomography (CT). At the same time, the iron single-atom material in the composite material simultaneously has peroxidase-like activity (POD) and catalase-like activity (CAT), which can respectively decompose hydrogen peroxide in the tumor microenvironment into toxic hydroxyl radicals or oxygen. Meanwhile, the material has good photothermal conversion ability and can absorb near-infrared light and convert it into heat for photothermal therapy of tumor cells. Finally, the flower-like structure of the nanomaterial can expose more active sites and improve the catalytic efficiency.

[0021] The present invention reasonably combines the structures and physicochemical properties of gold-platinum nanoparticles and iron single-atom nanomaterials to construct a gold-platinum-iron nanocomposite material that simultaneously has POD, CAT, and GOx activities and can achieve cascade catalysis. That is, through the CAT activity of the composite material, a large amount of hydrogen peroxide in the tumor microenvironment is decomposed to produce oxygen. While alleviating hypoxia inside the tumor, the oxygen can participate in the consumption of glucose as a substrate for glucose oxidation. The GOx activity exhibited by the gold-platinum nanoparticles can oxidize the glucose inside the tumor cells using the generated oxygen to produce hydrogen peroxide, and the hydrogen peroxide can be decomposed into oxygen by the CAT activity, achieving a cycle of self-producing oxygen and consuming glucose, thereby efficiently consuming the glucose inside the tumor cells. At the same time, the POD activity of the iron single-atom in the composite material can finally convert the hydrogen peroxide inside the tumor cells into toxic hydroxyl radicals to kill the tumor cells. The gold-platinum-iron nanocomposite material realizes the self-supply of hydrogen peroxide-oxygen-hydrogen peroxide and the cascade catalysis of oxygen-hydrogen peroxide-hydroxyl radicals, thus achieving the self-supply of oxygen and hydrogen peroxide during the reaction process. On the other hand, the material has good photothermal conversion ability and can convert light energy into heat under near-infrared light irradiation for photothermal therapy. The gold-platinum-iron flower-like nanocomposite material can achieve the diagnosis of tumors and the combined effects of tumor starvation therapy, chemodynamic therapy, and photothermal therapy. Hyaluronic acid (HA) is an acidic mucopolysaccharide with D-glucuronic acid and N-acetylglucosamine as disaccharide units, which has good biocompatibility and biodegradability and can actively target the CD44 receptor highly expressed on the surface of tumor cells and serves as the basis for targeted drug delivery.

[0022] The present invention can obtain a preparation method and application of a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability. Brief Description of the Drawings

[0023] Figure 1Schematic diagram of the catalytic function of the Au-Pt-Fe flower-like nanocomposite prepared in Example 1;

[0024] Figure 2 Scanning electron microscope (SEM) image of the Au-Pt-Fe flower-like nanocomposite prepared in Example 1;

[0025] Figure 3 Transmission electron microscope (TEM) image of the Au-Pt-Fe flower-like nanocomposite prepared in Example 1;

[0026] Figure 4 FT-IR image obtained in Example 1;

[0027] Figure 5 UV-Vis absorption spectrum image of POD activity in Example 1;

[0028] Figure 6 Image of the dissolved oxygen amount of CAT activity in Example 1;

[0029] Figure 7 Image of GOx activity in Example 1;

[0030] Figure 8 Image of the photothermal ability at different concentrations in Example 1;

[0031] Figure 9 Images of in vitro imaging of Au-Pt-Fe nanocomposites at different concentrations under CT and the fitting curves. Detailed implementation manners

[0032] Detailed implementation manner 1: A preparation method of an Au-Pt-Fe flower-like nanocomposite with cascade catalytic ability is carried out according to the following steps:

[0033] Step S1, synthesis of flower-like zeolitic imidazolate framework:

[0034] Using dopamine hydrochloride, zinc nitrate hexahydrate and 2-methylimidazole as raw materials for synthesis to obtain a flower-like zeolitic imidazolate framework material;

[0035] Step S2, first high-temperature pyrolysis:

[0036] Performing the first high-temperature pyrolysis on the flower-like zeolitic imidazolate framework material obtained in Step S1 under a nitrogen atmosphere to obtain the flower-like zeolitic imidazolate framework material after the first pyrolysis;

[0037] Step S3, second high-temperature pyrolysis:

[0038] The flower-like zeolitic imidazolate framework material obtained after the first pyrolysis in step S2 is subjected to a second high-temperature pyrolysis with ferrous sulfate and 2,2'-bipyridine under a nitrogen atmosphere to obtain a flower-like iron single-atom nanomaterial;

[0039] Step S4, loading gold-platinum nanoparticles:

[0040] The flower-like iron single-atom nanomaterial obtained in step S3 is mixed with chloroauric acid solution and chloroplatinic acid solution, and then reduced using a reducing agent to obtain a gold-platinum-iron flower-like nanomaterial loaded with gold-platinum nanoparticles;

[0041] Step S5, hyaluronic acid modification:

[0042] The gold-platinum-iron flower-like nanomaterial loaded with gold-platinum nanoparticles obtained in step S4 is modified with hyaluronic acid to obtain a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability.

[0043] Specific Embodiment 2: The difference between this embodiment and Specific Embodiment 1 is that the specific steps for synthesizing the flower-like zeolitic imidazolate framework material in step S1 are as follows:

[0044] Dissolve dopamine hydrochloride and zinc nitrate hexahydrate in ultrapure water to obtain a mixed solution a; dissolve 2-methylimidazole in a methanol solution to obtain a mixed solution b; mix the mixed solution a and the mixed solution b, stir under a water bath condition of 35-40 °C for 3-4 h, then repeatedly centrifuge and wash with methanol and ultrapure water for 3-5 times, and finally vacuum dry overnight at 60-80 °C to obtain a flower-like zeolitic imidazolate framework material; the mass ratio of dopamine hydrochloride, zinc nitrate hexahydrate to 2-methylimidazole is (1-3):10:(1-3).

[0045] Other steps are the same as those in Specific Embodiment 1.

[0046] Specific Embodiment 3: The difference between this embodiment and Specific Embodiment 1 or 2 is that the specific steps for the first high-temperature pyrolysis in step S2 are as follows:

[0047] Heat the flower-like zeolitic imidazolate framework material to 900-1000 °C under a nitrogen atmosphere, and pyrolyze it at a temperature of 900-1000 °C for 90-120 min to obtain the flower-like zeolitic imidazolate framework material after the first pyrolysis.

[0048] Other steps are the same as those in Specific Embodiment 1 or 2.

[0049] Specific Embodiment 4: The difference between this embodiment and any one of Specific Embodiments 1 to 3 is that the specific steps for the second high-temperature pyrolysis in step S3 are as follows:

[0050] The flower-shaped zeolite imidazole framework material after a single pyrolysis, ferrous sulfate and 2-2-bipyridine are dissolved in a 50% ethanol solution, stirred overnight, then washed with an ethanol solution, centrifuged and dried, and then heated to 900-950° C. in a nitrogen atmosphere, and pyrolyzed at a temperature of 900-950° C. for 120-150 min. After the pyrolysis is completed, it is cooled to room temperature to obtain a flower-shaped iron single-atom nanomaterial; the mass ratio of the flower-shaped zeolite imidazole framework material after a single pyrolysis, ferrous sulfate and 2-2-bipyridine is 2:(1-2):(2-4).

[0051] In this embodiment, the flower-like carbon skeleton material is subjected to high-temperature iron doping treatment to obtain a flower-like iron single-atom nanomaterial. The doped material has excellent POD activity and CAT activity, and can decompose hydrogen peroxide into toxic hydroxyl radicals and oxygen.

[0052] In this embodiment, a flower-like structured iron single atom nanomaterial is synthesized through secondary pyrolysis and in-situ synthesis, and gold-platinum nanoparticles are further synthesized in-situ on its surface. The composite material has POD, CAT and GOx activities and can carry out a continuous cascade catalytic reaction from glucose-hydrogen peroxide-oxygen.

[0053] The other steps are the same as those in Specific Embodiments 1 to 3.

[0054] Specific embodiment 5: The difference between this embodiment and specific embodiments 1 to 4 is that the specific steps of loading gold-platinum nanoparticles in step S4 are as follows:

[0055] The flower-shaped iron single-atom nanomaterial is dissolved in ultrapure water, and then a chloroauric acid solution and a chloroplatinic acid solution are added, and after being fully mixed, a reducing agent is added, and the mixture is stirred for 5 to 10 minutes at a temperature of 20 to 24° C., and then the mixture is centrifuged and washed with ultrapure water for 3 to 5 times to obtain a gold-platinum-iron loaded flower-shaped nanomaterial; the ratio of the mass of the flower-shaped iron single-atom nanomaterial, the volume of the chloroauric acid solution and the volume of the chloroplatinic acid solution is (0.2 to 0.4) mg: 1 μL: (0.5 to 2) μL.

[0056] The other steps are the same as those in Specific Embodiments 1 to 4.

[0057] Specific embodiment 6: The difference between this embodiment and specific embodiments 1 to 5 is that the specific steps of hyaluronic acid modification in step S5 are as follows:

[0058] Mix the gold-platinum-iron flower-like nanomaterial loaded with the payload with a hyaluronic acid solution, stir for 12 to 24 h under the conditions of avoiding light and at a temperature of 20 to 24 °C, and then centrifuge and wash with ultrapure water 3 to 5 times to obtain a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability; the ratio of the mass of the gold-platinum-iron flower-like nanomaterial loaded with the payload to the volume of the hyaluronic acid solution is 1 mg:(1 to 2) mL.

[0059] Other steps are the same as those in the first to fifth specific embodiments.

[0060] Specific embodiment seven: The difference between this embodiment and one of the first to sixth specific embodiments is that in step S1, the ratio of the mass of dopamine hydrochloride, the mass of zinc nitrate hexahydrate to the volume of ultrapure water is (1 to 3) mg:10 mg:0.14 mL, and the ratio of the mass of 2-methylimidazole to the volume of the methanol solution is (3.6 to 10.8) mg:0.625 mL;

[0061] In step S3, the ratio of the mass of the flower-like zeolitic imidazolate framework material after the first pyrolysis, the mass of ferrous sulfate, the mass of 2,2'-bipyridine to the volume of the ethanol solution is 2 mg:(1 to 2) mg:(2 to 4) mg:(0.2 to 0.3) mL;

[0062] In step S4, the ratio of the mass of the flower-like iron single-atom nanomaterial, the volume of ultrapure water to the volume of the reducing agent is (10 to 15) mg:(10 to 15) mL:(1 to 1.5) mL; the reducing agent is a sodium borohydride solution with a concentration of 1.5 to 2.0 mg / mL.

[0063] Other steps are the same as those in the first to sixth specific embodiments.

[0064] Specific embodiment eight: The difference between this embodiment and one of the first to seventh specific embodiments is that the stirring rate in step S1 is 300 to 400 rpm / min;

[0065] The heating rate in step S2 is 2 to 5 °C / min;

[0066] The heating rate in step S3 is 2 to 5 °C / min;

[0067] The stirring rate in step S4 is 1000 to 2000 rpm / min, and the centrifugation rate is 3000 to 5000 rpm / min;

[0068] The stirring rate in step S5 is 200 to 300 rpm / min.

[0069] Other steps are the same as those in the first to seventh specific embodiments.

[0070] Embodiment 9: The difference between this embodiment and any one of Embodiments 1 to 8 is that: in step S4, the concentration of the chloroauric acid solution is 48.6 - 97.2 mM, and the concentration of the chloroplatinic acid solution is 38.6 - 77.2 mM;

[0071] In step S5, the concentration of the hyaluronic acid solution is 1 - 2 mg / mL.

[0072] Other steps are the same as those in Embodiments 1 to 8.

[0073] Embodiment 10: Application of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability, the application of the gold-platinum-iron flower-like nanocomposite with cascade catalytic ability in the preparation of tumor diagnostic materials, tumor-targeted chemotherapeutic starvation therapy drugs and near-infrared photothermal synergistic therapy drugs.

[0074] The following examples are used to verify the beneficial effects of the present invention:

[0075] Example 1: A preparation method of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability is carried out according to the following steps:

[0076] Step S1: Synthesis of flower-like zeolitic imidazolate framework:

[0077] Dissolve 200 mg of dopamine hydrochloride and 1800 mg of zinc nitrate hexahydrate in 25.2 mL of ultrapure water to obtain a mixed solution a; dissolve 400 mg of 2-methylimidazole in 50 mL of methanol solution to obtain a mixed solution b; after mixing the mixed solution a and the mixed solution b, under the water bath condition of 40 °C, stir at a rate of 300 rpm / min for 3 h, then repeatedly centrifuge and wash with methanol and ultrapure water for 3 times, and finally vacuum dry overnight at 60 °C to obtain a flower-like zeolitic imidazolate framework material;

[0078] Step S2: First high-temperature pyrolysis:

[0079] Heat the flower-like zeolitic imidazolate framework material in a nitrogen atmosphere to 950 °C at a rate of 5 °C / min, and pyrolyze at 950 °C for 90 min to obtain a flower-like zeolitic imidazolate framework material after the first pyrolysis;

[0080] Step S3: Second high-temperature pyrolysis:

[0081] 100 mg of the flower-like zeolite imidazole framework material after primary pyrolysis, 50 mg of ferrous sulfate and 100 mg of 2-2-bipyridine were dissolved in 10 mL of 50% ethanol solution, stirred overnight, then washed with ethanol solution, centrifuged and dried, and then heated to 900°C at a rate of 5°C / min under a nitrogen atmosphere, and pyrolyzed at 900°C for 120 min. After the pyrolysis was completed, it was cooled to room temperature to obtain a flower-like iron single-atom nanomaterial;

[0082] Step S4, loading gold-platinum nanoparticles:

[0083] 10 mg of flower-like iron single-atom nanomaterial was dissolved in 10 mL of ultrapure water, and then 50 μL of chloroauric acid solution (concentration of 48.6 mM) and 62 μL of chloroplatinic acid solution (concentration of 38.6 mM) were added. After thorough mixing, 1 mL of sodium borohydride solution (concentration of 1.5 mg / mL) was added. The mixture was stirred at a rate of 1000 rpm / min for 10 min at a temperature of 24°C, and then centrifuged and washed 3 times with ultrapure water at a rate of 5000 rpm / min to obtain a loaded gold-platinum-iron flower-like nanomaterial, which was redissolved in ultrapure water and stored at 4°C in the dark.

[0084] Step S5, hyaluronic acid modification:

[0085] 10 mg of loaded gold-platinum-iron flower-like nanomaterials was mixed with 10 mL of hyaluronic acid solution (concentration of 1 mg / mL), stirred at 300 rpm / min for 24 h in a dark environment and at 24°C, and then centrifuged and washed three times with ultrapure water to remove excess hyaluronic acid to obtain a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability.

[0086] Figure 1 A schematic diagram showing the catalytic function of the gold-platinum-iron flower-shaped nanocomposite prepared in Example 1; Figure 1 As shown, the gold-platinum-iron flower-like nanocomposite first decomposes hydrogen peroxide into oxygen, and then the oxygen continues to react with glucose to produce gluconic acid and hydrogen peroxide. A part of the hydrogen peroxide continues to decompose into oxygen, and the other part decomposes into hydroxyl radicals.

[0087] Figure 2 : represents a scanning electron microscope (SEM) image of the gold-platinum-iron flower-shaped nanocomposite prepared in Example 1; Figure 2 As shown, after two pyrolysis steps, the material has a flower-like structure with uniform particle size. The flower-like structure can provide a large number of attachment sites for gold-platinum nanoparticles to increase the loading amount and thus improve the catalytic efficiency.

[0088] Figure 3Shows the transmission electron microscope (TEM) image of the gold-platinum-iron flower-like nanocomposite prepared in Example 1; as Figure 3 shown, the figure shows the original image, the atomic distributions of carbon, iron, gold, and platinum respectively. It can be seen that the material morphology is a flower-like loose structure, and gold-platinum nanoparticles are attached to the surface. The energy spectrum image shows that the distribution of each element is uniform. Since gold-platinum nanoparticles are not stable and will spontaneously aggregate, resulting in an increase in particle size, and their catalytic activity will decrease with the increase in particle size. The flower-like structure effectively separates the gold-platinum nanoparticles in space, preventing the decrease in activity caused by the aggregation of gold-platinum nanoparticles to a certain extent.

[0089] Figure 4 Shows the Fourier transform infrared spectroscopy (FT-IR) image obtained in Example 1; as Figure 4 shown, compared with the FT-IR spectrum of the gold-platinum-iron nanomaterial, in the FT-IR spectrum of the hyaluronic acid-modified gold-platinum-iron composite nanomaterial, the characteristic peak of C-H at 2891 cm -1 and the characteristic peak of COO -1 at 1415 cm - can be seen, which are consistent with the characteristic peaks of the hyaluronic acid molecule, indicating the successful modification of hyaluronic acid.

[0090] Figure 5 Shows the ultraviolet-visible absorption spectrum image of POD activity in Example 1; as Figure 5 shown, the final concentrations of hydrogen peroxide are 0.5 mM, 1 mM, 2 mM, 4 mM, 8 mM, 10 mM, 25 mM, 50 mM, and 100 mM respectively. The results show that with the increase in the concentration of hydrogen peroxide, the initial reaction rate shows an increasing trend, and the ultraviolet absorption at 653 nm increases significantly. It is calculated that the maximum reaction rate Vmax = 5.9×10 -6 Ms -1 , Km = 6.6 mM.

[0091] Note: Km is the Michaelis constant in enzyme kinetics, which is the substrate concentration when the enzyme-catalyzed reaction rate reaches half of Vmax.

[0092] Figure 6 Shows the reactive oxygen dissolution amount image of CAT activity in Example 1; as Figure 6 shown, the final concentrations of hydrogen peroxide are 1 mM, 2 mM, 4 mM, 6 mM, 8 mM, and 10 mM respectively. The results show that with the increase in the concentration of hydrogen peroxide, the oxygen content in the reaction system increases with time, indicating that the gold-platinum-iron nanocomposite can catalyze the decomposition of hydrogen peroxide to produce oxygen. It is calculated that Vmax = 19.3 mgL -1 min -1 , Km = 10.2 mM.

[0093] Figure 7 It represents the GOx activity image in Example 1; as Figure 7 shown, under the condition of a 37 °C water bath, DNS reagent was used to detect the consumption of glucose in the reaction system. The final concentrations of the gold-platinum-iron nanocomposite were 0 μg / mL, 100 μg / mL, 150 μg / mL, 200 μg / mL, and 250 μg / mL respectively. The results showed that with the increase in the concentration of the gold-platinum-iron nanocomposite, after 24 hours, the glucose concentration decreased significantly, and the glucose concentrations decreased to approximately 85.68%, 70.45%, 55.29%, and 47.74% of the control group concentration respectively, indicating that the gold-platinum-iron nanocomposite could effectively consume glucose in the reaction system.

[0094] Figure 8 It represents the images of the photothermal ability at different concentrations in Example 1; as Figure 8 shown, under the irradiation of 808 nm near-infrared light with a power of 1 W / cm 2 ², the temperatures of the aqueous solutions of the gold-platinum-iron nanocomposite at different concentrations all increased significantly (the final concentrations were 31.25 μg / mL, 62.5 μg / mL, 125 μg / mL, 250 μg / mL, and 500 μg / mL respectively). After 5 minutes of irradiation, the temperatures reached 41 °C, 50.4 °C, 61.7 °C, 64 °C, and 73.4 °C respectively. The calculated photothermal conversion efficiency was 36.9%, indicating that the gold-platinum-iron nanocomposite had good photothermal conversion ability.

[0095] Figure 9 It represents the imaging images and fitting curves of the gold-platinum-iron nanocomposite at different concentrations in vitro under CT; as Figure 9 shown, with the increase in the concentration of the nanocomposite, the CT value also increased. The concentration-CT value fitting curve was y = 10.12 + 26.75, indicating that there was a good linear relationship between the concentration of the gold-platinum-iron nanocomposite and CT.

Claims

1. A method for preparing a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability, characterized in that The preparation method is carried out according to the following steps: Step S1, synthesis of flower-like zeolitic imidazolate framework: Using dopamine hydrochloride, zinc nitrate hexahydrate and 2-methylimidazole as raw materials for synthesis to obtain a flower-like zeolitic imidazolate framework material; Step S2, the first high-temperature pyrolysis: Performing the first high-temperature pyrolysis on the flower-like zeolitic imidazolate framework material obtained in step S1 under a nitrogen atmosphere to obtain the flower-like zeolitic imidazolate framework material after the first pyrolysis; Step S3, the second high-temperature pyrolysis: Performing the second high-temperature pyrolysis on the flower-like zeolitic imidazolate framework material after the first pyrolysis obtained in step S2, ferrous sulfate and 2,2'-bipyridine under a nitrogen atmosphere to obtain a flower-like iron single-atom nanomaterial; Step S4, loading gold-platinum nanoparticles: Mixing the flower-like iron single-atom nanomaterial obtained in step S3 with chloroauric acid solution and chloroplatinic acid solution, and then reducing with a reducing agent to obtain a gold-platinum-iron flower-like nanomaterial; Step S5, hyaluronic acid modification: Modifying the gold-platinum-iron flower-like nanomaterial obtained in step S4 with hyaluronic acid to obtain a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability.

2. The preparation method of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability according to claim 1, characterized in that The specific steps for synthesizing the flower-like zeolitic imidazolate framework material in step S1 are as follows: Dissolving dopamine hydrochloride and zinc nitrate hexahydrate in ultrapure water to obtain a mixed solution a; dissolving 2-methylimidazole in a methanol solution to obtain a mixed solution b; mixing the mixed solution a and the mixed solution b, stirring for 3 - 4 h under a water bath condition of 35 - 40 °C, then repeatedly centrifuging and washing with methanol and ultrapure water for 3 - 5 times, and finally drying under vacuum at 60 - 80 °C overnight to obtain the flower-like zeolitic imidazolate framework material; the mass ratio of dopamine hydrochloride, zinc nitrate hexahydrate to 2-methylimidazole is (1 - 3):10:(1 - 3).

3. The preparation method of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability according to claim 1, characterized in that The specific steps for the first high-temperature pyrolysis in step S2 are as follows: Heating the flower-like zeolitic imidazolate framework material to 900 - 1000 °C under a nitrogen atmosphere and pyrolyzing for 90 - 120 min at a temperature of 900 - 1000 °C to obtain the flower-like zeolitic imidazolate framework material after the first pyrolysis.

4. The preparation method of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability according to claim 1, characterized in that The specific steps for the second high-temperature pyrolysis in step S3 are as follows: Dissolving the flower-like zeolitic imidazolate framework material after the first pyrolysis, ferrous sulfate and 2,2'-bipyridine in a 50% ethanol solution, stirring overnight, then washing, centrifuging and drying with an ethanol solution, and then heating to 900 - 950 °C under a nitrogen atmosphere and pyrolyzing for 120 - 150 min at a temperature of 900 - 950 °C, and cooling to room temperature after the pyrolysis to obtain a flower-like iron single-atom nanomaterial; the mass ratio of the flower-like zeolitic imidazolate framework material after the first pyrolysis, ferrous sulfate to 2,2'-bipyridine is 2:(1 - 2):(2 - 4).

5. The preparation method of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability according to claim 1, characterized in that The specific steps for loading gold-platinum nanoparticles in step S4 are as follows: The flower-shaped iron single-atom nanomaterial is dissolved in ultrapure water, and then a chloroauric acid solution and a chloroplatinic acid solution are added, and after being fully mixed, a reducing agent is added, and the mixture is stirred for 5 to 10 minutes at a temperature of 20 to 24° C., and then the mixture is centrifuged and washed with ultrapure water for 3 to 5 times to obtain a gold-platinum-iron loaded flower-shaped nanomaterial; the ratio of the mass of the flower-shaped iron single-atom nanomaterial, the volume of the chloroauric acid solution and the volume of the chloroplatinic acid solution is (0.2 to 0.4) mg: 1 μL: (0.5 to 2) μL.

6. The preparation method of a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability according to claim 1, characterized in that The specific steps of hyaluronic acid modification in step S5 are as follows: The loaded gold-platinum-iron flower-shaped nanomaterial is mixed with a hyaluronic acid solution, stirred for 12 to 24 hours in a dark environment at a temperature of 20 to 24° C., and then washed by centrifugation with ultrapure water for 3 to 5 times to obtain a gold-platinum-iron flower-shaped nanocomposite material with cascade catalytic ability; the ratio of the mass of the loaded gold-platinum-iron flower-shaped nanomaterial to the volume of the hyaluronic acid solution is 1 mg: (1 to 2) mL.

7. The preparation method of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability according to claim 2, 4 or 5, characterized in that The ratio of the mass of dopamine hydrochloride, the mass of zinc nitrate hexahydrate and the volume of ultrapure water in step S1 is (1-3) mg:10 mg:0.14 mL, and the ratio of the mass of 2-methylimidazole to the volume of the methanol solution is (3.6-10.8) mg:0.625 mL; The ratio of the mass of the flower-like zeolite imidazole framework material after the primary pyrolysis in step S3, the mass of ferrous sulfate, the mass of 2-2-bipyridine and the volume of the ethanol solution is 2 mg: (1-2) mg: (2-4) mg: (0.2-0.3) mL; The ratio of the mass of the flower-shaped iron single-atom nanomaterial, the volume of ultrapure water and the volume of the reducing agent described in step S4 is (10-15) mg: (10-15) mL: (1-1.5) mL; the reducing agent is a sodium borohydride solution with a concentration of 1.5-2.0 mg / mL.

8. A method for preparing a gold-platinum-iron flower-like nanocomposite material with cascade catalytic ability according to claim 2, 3, 4, 5 or 6, characterized in that In step S1, the stirring rate is 300-400 rpm / min; In step S2, the heating rate is 2-5°C / min; In step S3, the heating rate is 2-5°C / min; In step S4, the stirring rate is 1000-2000 rpm / min, and the centrifugal rate is 3000-5000 rpm / min; The stirring rate in step S5 is 200-300 rpm / min.

9. The preparation method of a gold-platinum-iron flower-like nanocomposite with cascade catalytic ability according to claim 5 or 6, characterized in that The concentration of the chloroauric acid solution in step S4 is 48.6-97.2 mM, and the concentration of the chloroplatinic acid solution is 38.6-77.2 mM; The concentration of the hyaluronic acid solution in step S5 is 1-2 mg / mL.

10. Use of a gold-platinum-iron flower-like nanocomposite having cascade catalytic ability prepared by the method according to any one of claims 1-9, characterized in that The gold-platinum-iron flower-shaped nanocomposite material with cascade catalytic ability is used in the preparation of tumor diagnostic materials, tumor targeted chemotherapy starvation therapy drugs and near-infrared photothermal synergistic therapy drugs.

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