Platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial as well as preparation method and application thereof

Abstract

The invention discloses a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial as well as a preparation method and application thereof, and belongs to the field of biological materials. The composite nano material comprises platinum nano particles, nano hafnium oxide and graphene quantum dots, the platinum nanoparticles and the nano hafnium oxide are dispersed in the graphene quantum dots; the graphene quantum dots wrap the peripheries of the platinum nanoparticles; the graphene quantum dots wrap the periphery of the nano hafnium oxide. The composite nano material provided by the invention can quickly decompose hydrogen peroxide to form oxygen bubbles, and can effectively improve the microenvironment of high-concentration hydrogen peroxide and hypoxia in tumors, thereby enhancing the radiotherapy sensitization effect of the nano composite material; the high-activity PtNPs with the surface effect is oxidized and decomposed to release cancer cell toxic ionic platinum or related bivalent platinum complexes to generate a chemotherapy effect; the composite nano material integrates radiotherapy sensitization and tumor microenvironment improvement, and is a medicine for combined treatment of tumors with a good application prospect.

Description

Technical Field

[0001] The present application relates to the field of biomaterial technology, and in particular to a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial and a preparation method and application thereof. Background Art

[0002] Radiotherapy for tumors is a local treatment method. The radiation used includes α, β, and γ rays produced by radioisotopes and X-rays, electron beams, proton beams, and other particle beams produced by various X-ray therapy machines or accelerators. At present, hospitals often use high-energy X-rays and γ-rays for radiotherapy. The mechanism is that the rays interact with matter to produce photoelectrons and secondary electrons. The electrons interact with surrounding matter to generate reactive oxygen or free radicals. Electrons, reactive oxygen, and free radicals induce apoptosis of cancer cells and destroy tumor tissue. However, radiotherapy has its own limitations: due to the heterogeneity of tumors and radiation resistance caused by various reasons, the radiation dose has to be increased in clinical practice to improve the efficacy, and high radiation doses are harmful to the human body. How to reduce the radiation dose is a key issue that needs to be solved in radiotherapy. Among them, enhancing the effect of radiotherapy by using radiosensitizers is one of the feasible solutions.

[0003] The radiation dose deposition in tumor tissue is related to the interaction or absorption capacity of high-energy rays and tumor tissue. The intervention of substances containing elements with high atomic numbers and high electron density can increase the radiation dose deposition of high-energy rays in tumor tissue. This radiosensitization effect increases the radiation damage effect of high-energy radiation on tumor cells while reducing radiation damage to normal tissues. On the other hand, the hypoxic environment of tumor tissue makes it difficult for the deposited high-energy rays to produce more reactive oxygen or free radicals, thereby reducing the radiosensitization effect. Therefore, how to improve the hypoxic environment of tumor tissue is another key issue that needs to be solved in radiosensitization therapy.

[0004] The atomic number of hafnium is 72 and its density is 9.7 g / cm 3 , has good X-ray or γ-ray deposition ability, so it is used for radiotherapy sensitization. Among them, nano hafnium oxide (HfO 2-x ,0≤x<1) is a radiotherapy sensitizer with great application prospects, because nano-hafnium oxide is resistant to strong acids and alkalis, easy to excrete, and has no toxic side effects on the human body, while other nanoparticles containing heavy metals may easily decompose metal ions in the human body and produce toxicity. However, how to improve the hypoxic environment of tumor tissue and how to enhance the radiotherapy sensitization effect of nano-hafnium oxide have become urgent problems to be solved today. Summary of the invention

[0005] In view of this, the present application provides a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial and its preparation method and application, which are mainly used to improve the hypoxic microenvironment of tumor tissue and enhance the radiotherapy sensitization effect of nano hafnium oxide.

[0006] On the one hand, the present application provides a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial, which includes platinum nanoparticles, nano hafnium oxide and graphene quantum dots;

[0007] The platinum nanoparticles and the hafnium oxide nanoparticles are dispersed in the graphene quantum dots;

[0008] The graphene quantum dots are wrapped around the periphery of the platinum nanoparticles;

[0009] The graphene quantum dots are wrapped around the periphery of the nano-hafnium oxide.

[0010] The platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial of the present application includes platinum nanoparticles, nano-hafnium oxide and graphene quantum dots; platinum nanoparticles and nano-hafnium oxide are dispersed in graphene quantum dots; platinum nanoparticles and nano-hafnium oxide are protected by graphene quantum dots and do not agglomerate. Specifically, platinum nanoparticles and nano-hafnium oxide are protected by peripheral graphene quantum dots, and the formed nanocomposite is a water-soluble nanomaterial. The carboxyl, hydroxyl, amino and other groups in the graphene quantum dots increase the dispersibility and solubility of the nanocomposite. The purified product is evenly dispersed in an aqueous solution, and the water solubility is greater than 80 mg / mL. All solutes can pass through a microporous filter membrane with a pore size of 220 nm, and there is no precipitation phenomenon after being placed for 2 months.

[0011] The nano hafnium oxide selected in this application is a radiotherapy sensitizer with great application prospects, but its anti-tumor application faces two problems: 1) Improving the stability and solubility of nano hafnium oxide and effectively solving the problem of clinical radiotherapy sensitization of nano hafnium oxide; 2) The hypoxic environment of tumor tissue makes it difficult for the high-energy rays deposited by nano hafnium oxide to produce more active oxygen or free radicals, thereby reducing the radiosensitization effect.

[0012] In order to solve the above shortcomings of the prior art, the present application uses highly soluble and biocompatible graphene quantum dots (GQDs) to effectively protect nano-hafnium oxide, thereby preventing the aggregation of nano-hafnium oxide and promoting its dissolution. At the same time, GQDs also have a radiosensitization effect; the internal mechanism is: GQDs with semiconductor properties produce reactive oxygen under the action of high-energy rays, causing lysosomes to rupture, releasing tissue proteases, and causing cell apoptosis. Nano-hafnium oxide / graphene quantum dots (HfO 2-x @GQDs) nanocomposites have good water solubility and biocompatibility, and these properties can solve the problem of clinical radiotherapy sensitizer medication.

[0013] In order to improve the hypoxic microenvironment of tumor tissue and enhance HfO 2-x @GQDs nanocomposite radiosensitization effect, this application in HfO2-x Platinum nanoparticles (PtNPs) were introduced into the GQDs nanocomposite to form PtNPs, HfO 2-x @GQDs nanocomposite. PtNPs with catalase activity can convert high-concentration hydrogen peroxide ([H2O2] = 100μM ~ 1mM) in tumor cells into oxygen molecules, effectively improving the hypoxic microenvironment of tumor tissue. In addition, in the special microenvironment of the tumor (such as high acidity, high hydrogen peroxide concentration, etc.), the highly active PtNPs with surface effects are oxidized and decomposed, releasing ionic platinum or related divalent platinum complexes that are toxic to cancer cells, producing a chemotherapeutic effect. PtNPs,HfO 2-x @GQDs nanocomplex combines radiotherapy sensitization, improvement of tumor microenvironment and chemotherapy. It is a very promising drug for combined tumor treatment and is expected to achieve a combined treatment effect of radiotherapy-chemotherapy 1+1>2.

[0014] Optionally, the mass percentage of the platinum nanoparticles in the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial is 10wt% to 15wt%.

[0015] Optionally, the mass percentage of the platinum nanoparticles in the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial is selected from any value of 10wt%, 11wt%, 12wt%, 13wt%, 14wt%, 15wt% or any range between the two.

[0016] Optionally, the platinum nanoparticles in the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial have a (11 1) crystal plane, and the lattice spacing d is

[0017] Optionally, all solutes in the aqueous solution of the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial pass through a microporous filter membrane with a pore size of 220 nm.

[0018] Optionally, the water solubility of the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial is 80 to 250 mg / mL.

[0019] Optionally, the water solubility of the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial is selected from any value among 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250 or any range between two values, in mg / mL.

[0020] Optionally, the particle size of the platinum nanoparticles in the platinum nanoparticle / hafnium oxide / graphene quantum dot composite nanomaterial is 2 to 8 nm.

[0021] Optionally, the particle size of the platinum nanoparticles in the platinum nanoparticle / hafnium oxide / graphene quantum dot composite nanomaterial is any value among 2, 3, 4, 5, 6, 7, 8 or a range value between any two of them, in nm.

[0022] In a second aspect, the present application provides a method for preparing the above-mentioned platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial, comprising the following steps:

[0023] S1: Obtaining hafnium oxide / graphene quantum dot composite nanomaterials;

[0024] S2: subjecting a mixture containing the hafnium oxide / graphene quantum dot composite nanomaterial and a platinum source to in-situ photoreduction to obtain a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial.

[0025] In this application, platinum ions anchored in graphene quantum dots containing nitrogen, sulfur, oxygen, etc. are photoreduced in situ, so that the platinum ions are slowly reduced to form platinum nanoparticles and attached to the hafnium oxide / graphene quantum dot matrix. The basic principle is: the electrons and holes of the semiconductor are separated by light, and a hole sacrificial agent is added to generate more electrons. The electrons reduce the platinum ions anchored in the graphene quantum dots, and the formed platinum nanoparticles are protected, and the obtained platinum particles / hafnium oxide / graphene quantum dot composite nanomaterials. After the photoreaction, the added hole sacrificial agent ethanol or methanol can be removed by processes such as rotary evaporation and freeze-drying; unreacted platinum compounds such as sodium chloroplatinite, chloroplatinic acid, and sodium chloroplatinate can be removed by washing with ethanol.

[0026] Optionally, in step S2, the mass ratio of the hafnium oxide / graphene quantum dot composite nanomaterial to the platinum source is 3 to 4:1.

[0027] Optionally, in step S2, the mass ratio of the hafnium oxide / graphene quantum dot composite nanomaterial to the platinum source is selected from any value of 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0 or any range between two of them.

[0028] Optionally, the mixing ratio of the hafnium oxide / graphene quantum dot composite nanomaterial, the platinum source and the hole sacrificial agent is (1-1.5) g: (0.3-0.4) g: (15-25) mL.

[0029] Optionally, in step S2, the light source in the in-situ photoreduction process is selected from near-ultraviolet light of a xenon lamp with a wavelength of 300 to 400 nm.

[0030] The light source of the present application does not use visible light or infrared light to prevent the solution from being overheated and causing platinum black precipitation.

[0031] Optionally, the temperature of the in-situ photoreduction is -16°C to -10°C, and the illumination time is 1.5 to 2.5 hours.

[0032] Optionally, the temperature of the in situ photoreduction is any value among -16°C, -15°C, -14°C, -13°C, -12°C, -11°C, -10°C, or any range between two of them.

[0033] The photoreduction reaction of the present application is carried out at low temperature as much as possible to ensure the slow formation of ultrafine platinum nanoparticles so as to exert the chemotherapeutic effect of the platinum nanoparticles.

[0034] Optionally, the illumination time of the in situ photoreduction is selected from any value among 1.5, 1.8, 2.0, 2.2, 2.5 or any range between two values, in units of h.

[0035] Optionally, in step S2, the platinum source is selected from at least one of sodium chloroplatinite, potassium chloroplatinite, ammonium chloroplatinite, platinum tetrachloride, chloroplatinic acid and sodium chloroplatinate; preferably at least one of sodium chloroplatinite, chloroplatinic acid and sodium chloroplatinate that is soluble in both water and ethanol or methanol.

[0036] Optionally, the hole sacrificial agent in the in-situ photoreduction process is a volatile organic solvent; preferably, the hole sacrificial agent is ethanol and / or methanol.

[0037] Optionally, the product after the in-situ photoreduction is further subjected to a purification process to obtain a purified composite nanomaterial; the purification process includes vacuum rotary evaporation, ultrafiltration, washing, and vacuum freeze-drying.

[0038] Optionally, in step S1, the method for preparing the hafnium oxide / graphene quantum dot composite nanomaterial comprises:

[0039] A mixture containing a hafnium source, an organic anion and an alkaline precursor undergoes a solvent thermal reaction under closed conditions to obtain a composite nanomaterial.

[0040] The basic principles and steps of hafnium oxide / graphene quantum dot composite nanomaterials in this application are as follows:

[0041] 1) Organic anions effectively complex and protect hafnium ions, preventing hafnium ions from quickly generating precipitation such as hafnium hydroxide and hafnium oxide in neutral or alkaline solutions;

[0042] 2) Under the action of an alkaline precursor, the hafnium complex forms nano-hafnium oxide under high temperature and high pressure conditions, and at the same time, organic molecules gathered around the hafnium ions polymerize to form highly soluble graphene quantum dots, thereby obtaining a highly soluble hafnium oxide / graphene quantum dot composite nanomaterial;

[0043] 3) Purification of hafnium oxide / graphene quantum dot composite nanomaterials: The solution after the solvothermal reaction is filtered, nanofiltered, etc. to remove large particle precipitation, volatile substances, small organic molecules, inorganic salts and other impurities, and then freeze-dried to obtain pure hafnium oxide / graphene quantum dot composite nanomaterials.

[0044] Optionally, the hafnium source is selected from at least one of hafnium chloride, hafnium oxychloride and hafnium sulfate.

[0045] Optionally, the organic anion is selected from a citrate anion and / or an ethylenediaminetetraacetic acid anion.

[0046] Optionally, the alkaline precursor is selected from at least one of ammonia water, urea, thiourea and dicyandiamide; and the solvent is selected from deionized water.

[0047] Optionally, the temperature of the solvent thermal reaction is 180 to 250° C.; the time of the solvent thermal reaction is 8 to 24 hours.

[0048] Optionally, the product after the solvent thermal reaction is further subjected to a purification process to obtain a purified composite nanomaterial; the purification process includes filtration, vacuum rotary evaporation, and ultrafiltration.

[0049] The hafnium oxide / graphene quantum dot composite nanomaterial provided in the present application preferably has the following characteristics:

[0050] The composite material includes nano hafnium oxide and graphene quantum dots;

[0051] The chemical formula of the nano hafnium oxide is HfO 2-x , where 0≤x<1;

[0052] The graphene quantum dots are wrapped around the periphery of the nano-hafnium oxide. Optionally, the content of the nano-hafnium oxide in the composite nano-material is more than 45wt%.

[0053] Optionally, the nano-hafnium oxide / graphene quantum dot composite nanomaterial is observed and analyzed by high-resolution transmission electron microscopy, and the nano-hafnium oxide has a (-1 1 1) crystal plane and a lattice spacing of Nano-hafnium oxide has a (1 1 1) crystal plane and a lattice spacing of Graphene quantum dots have a (1 0 2) crystal plane and a lattice spacing of

[0054] Optionally, the particle size of the nano hafnium oxide is 2-5 nm.

[0055] Optionally, all solutes in the aqueous solution of the nano-hafnium oxide / graphene quantum dot composite nanomaterial pass through a microporous filter membrane with a pore size of 220 nm.

[0056] Optionally, the water solubility of the nano-hafnium oxide / graphene quantum dot composite nanomaterial is greater than 80 mg / mL.

[0057] Optionally, the water solubility of the nano-hafnium oxide / graphene quantum dot composite nanomaterial is 80 to 250 mg / mL.

[0058] Optionally, the graphene quantum dots contain carboxyl, hydroxyl, amino, or pyrrole.

[0059] The present application utilizes highly soluble and biocompatible graphene quantum dots (GQDs) to effectively protect nano-hafnium oxide, prevent the aggregation of nano-hafnium oxide and promote its dissolution. At the same time, GQDs also have a radiotherapy sensitization effect. Nano-hafnium oxide is protected by peripheral graphene quantum dots, and the formed nanocomposite is a water-soluble nanomaterial. The carboxyl, hydroxyl, amino and other groups in the graphene quantum dots increase the dispersibility and solubility of the nanocomposite. The purified product is evenly dispersed in a pure water solvent, with a water solubility greater than 80 mg / mL. All solutes can pass through a microporous filter membrane with a pore size of 220 nm, and there is no precipitation phenomenon after being placed for 2 months.

[0060] In a third aspect, the present application provides the use of the above-mentioned platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial or the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial obtained by the above-mentioned preparation method in the preparation of anti-tumor drugs.

[0061] Compared with the prior art, this application has the following beneficial effects:

[0062] The hafnium oxide / graphene quantum dot composite nanomaterial provided by the present application cannot decompose hydrogen peroxide, while the synthesized platinum particles / hafnium oxide / graphene quantum dot composite nanomaterial can quickly decompose hydrogen peroxide to form oxygen bubbles, indicating that the platinum nanoparticles in the material have a catalase effect, which can effectively improve the microenvironment of high concentrations of hydrogen peroxide and hypoxia in tumors, thereby enhancing the radiosensitization effect of the nanocomposite material. In addition, the synthesized hafnium oxide / graphene quantum dot composite nanomaterial has no cancer cell toxicity, while the synthesized platinum particles / hafnium oxide / graphene quantum dot composite nanomaterial has a chemotherapeutic effect. Therefore, the platinum particles / hafnium oxide / graphene quantum dot composite nanomaterial combines radiosensitization, improvement of tumor microenvironment, and chemotherapy, and is a drug for combined treatment of tumors with great application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] Figure 1 It is HfO prepared in Example 1 of the present application 2-x @TEM image of GQDs;

[0064] Figure 2 It is HfO prepared in Example 1 of the present application 2-x @Infrared spectrum of GQDs;

[0065] Figure 3 The PtNPs, HfO prepared in Example 5 of the present application 2-x @Photoreaction device diagram of GQDs;

[0066] Figure 4 The PtNPs prepared in Example 5 of the present application, HfO 2-x @Transmission electron microscopy image of GQDs. DETAILED DESCRIPTION

[0067] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0068] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0069] The test methods and instruments used in the embodiments of the present application include:

[0070] (1) Testing HfO by high temperature burning method 2-x @The content of hafnium oxide in the GQDs sample: The sample was burned in a tube furnace at 800°C, and the graphene quantum dots in the nanocomposite were converted into gas, leaving white hafnium oxide powder.

[0071] (2) Metal content determination: Avio220Max plasma emission spectrometer, used to determine PtNPs, HfO 2-x @Pt content in GQDs.

[0072] (3) Transmission electron microscopy test and analysis instrument: Tecnai G2 F20 S-TWIN TMP transmission electron microscope. The sample is dissolved in an ethanol-deionized water mixture, dropped into the carbon film, and then vacuum-dried for morphology and crystallization observation.

[0073] (4) Infrared spectrum test and analysis instrument: VERTEX70 Fourier transform infrared spectrometer, recording

[0074] Example 1 (HfO 2-x @GQDs)

[0075] HkDJ 2-x Preparation of @GQDs: Weigh 6 mmol HfOCl2 .8H2O and 18mmol citric acid were placed in a polytetrafluoroethylene liner of a reactor (volume 100 ml), 45 ml of deionized water was added, ultrasonically dissolved for 10 minutes, and then 15 ml of 30% ammonia water was added, and then hydrothermally reacted at 180°C for 10 hours. After the reaction solution was naturally cooled to room temperature, a very small amount of orange-yellow large particles were removed by suction filtration through a 200nm filter membrane. The filtrate was diluted and the nanomaterial was purified using a tangential flow nanofiltration device (3KDa dialysis bag). The aqueous solution after nanofiltration was vacuum rotary evaporated and vacuum freeze-dried to obtain 1.95 grams of light yellow solid, HfO 2-x @GQDs. HfO 2-x @GQDs water solubility is 180mg / mL.

[0076] Transmission electron microscopy confirmed that HfO 2-x @GQDs features (such as Figure 1 ): High-resolution transmission electron microscopy observed the (-1 1 1) crystal plane of monoclinic hafnium oxide (lattice spacing d is ) and (1 1 1) planes (lattice spacing d is ), in addition, the (1 0 2) crystal plane of graphene quantum (lattice spacing d is ).

[0077] Example 2 (PtNPs, HfO 2-x @GQDs)

[0078] PtNPs,HfO 2-x Preparation of GQDs: Weigh more than 1.2 g of HfO 2-x @GQDs (prepared in Example 1) and 0.35 g of sodium chloroplatinate were placed in a photoreactor with a cold trap, 40 ml of water was added, the solution was stirred, and -15°C ethanol solution was passed into the cold trap to cool the reaction solution, and then 20 ml of ethanol was added to the reaction solution. The reaction solution was irradiated with a near-ultraviolet (300-400 nm) xenon lamp light source ( Figure 2 ), the reaction solution gradually changed from brown to brown, and almost no precipitation was generated, indicating that platinum nanoparticles were gradually generated and attached to the water-soluble HfO 2-x @GQDs substrate. After 2 hours of photoreaction, stop irradiation. Remove ethanol by vacuum rotary evaporation at low temperature (40-50°C), and remove a small amount of black precipitate by ultracentrifugation (9000rpm, 4min) of the obtained aqueous solution. After that, vacuum freeze-dry the aqueous solution to obtain a brown-black solid, which was washed with ethanol several times and vacuum freeze-dried again to obtain 1.35g of brown-black solid PtNPs, HfO 2-x @GQDs. PtNPs, HfO 2-x The water solubility of @GQDs is 160 mg / mL.

[0079] The plasma emission spectroscopy test showed that PtNPs, HfO 2-x The platinum content in @GQDs is 12.62wt%.

[0080] Transmission electron microscopy confirmed that PtNPs, HfO 2-x @GQDs features( Figure 3 ): High-resolution transmission electron microscopy observed the (-1 1 1) crystal plane of hafnium oxide (lattice spacing d is ) and the (1 1 1) plane of platinum nanoparticles (lattice spacing d is ).

[0081] Example 3 (PtNPs, HfO 2-x @GQDs)

[0082] PtNPs,HfO 2-x Preparation of GQDs: Weigh more than 1.2 g of HfO 2-x @GQDs (prepared in Example 1) and 0.35 g of chloroplatinic acid ammonium were placed in a photoreactor with a cold trap, 40 ml of water was added, the solution was stirred, and -15°C ethanol solution was passed into the cold trap to cool the reaction solution, and then 20 ml of ethanol was added to the reaction solution. The reaction solution was irradiated with a near-ultraviolet (300-400nm) xenon lamp light source, and the reaction solution gradually changed from brown-yellow to brown-black, with almost no precipitation generated. After 2 hours of photoreaction, the illumination was stopped. The ethanol was removed by vacuum rotary evaporation at low temperature (40-50°C), and the obtained aqueous solution was subjected to ultracentrifugation (9000rpm, 4min) to remove a small amount of black precipitate. Afterwards, the aqueous solution was vacuum freeze-dried to obtain a brown-black solid, which was washed with ethanol several times and vacuum freeze-dried again to obtain 1.26 g of brown-black solid PtNPs, HfO 2-x @GQDs. PtNPs, HfO 2-x The water solubility of @GQDs is 180 mg / mL.

[0083] The plasma emission spectroscopy test showed that PtNPs, HfO 2-x The platinum content in @GQDs is 11.36wt%.

[0084] Transmission electron microscopy confirmed that PtNPs, HfO 2-x @GQDs features (with Figure 3 Similar): High-resolution transmission electron microscopy observed the (-1 1 1) crystal plane of hafnium oxide (lattice spacing d is ) and the (1 1 1) plane of platinum nanoparticles (lattice spacing d is ).

[0085] Example 4

[0086] In vitro cancer cell proliferation inhibition test: After different concentrations of the test substance were applied to human tumor cells (cell number was 3K) for 3 days, the absorbance value was measured using the sulforhodamine B (SRB) method to calculate the half inhibitory concentration IC 50 .

[0087] First, HfO 2-x @GQDs precursors have no ability to inhibit cancer cell proliferation, and even at high concentrations (>160μg / mL), the inhibitory power is less than 5%, indicating that HfO 2-x @GQDs have almost no cytotoxicity. Table 1 shows PtNPs, HfO 2-x @IC of GQDs chemotherapy drugs (prepared in Example 2) on various human cancer cells 50 The values, calculated based on the platinum content, were all less than 2.0 μgPt / mL, indicating that platinum nanoparticles can effectively kill various types of human cancer cells.

[0088] Table 1. PtNPs, HfO 2-x In vitro proliferation inhibition test of GQDs on different human cancer cells

[0089] Cell lines <![CDATA[IC 50 (μgPt / mL)]]> Hela 0.253±0.042 HepG2 0.876±0.094 MDA-MB-231 1.853±0.114 A549 1.236±0.065 HT29 1.146±0.073

[0090] This application is based on hafnium oxide / graphene quantum dots (HfO 2-x @GQDs) composite, platinum nanoparticles (PtNPs) were introduced by in situ photoreduction to form PtNPs, HfO 2-x @GQDs composite nanomaterials. The highly soluble and biocompatible graphene quantum dots (GQDs) in the composite nanomaterials effectively protect nano-hafnium oxide, prevent the aggregation of nano-hafnium oxide and promote its dissolution, solving the problem of drug use for clinical radiosensitization of nano-hafnium oxide. At the same time, PtNPs effectively improve the hypoxic microenvironment of tumor tissue, thereby enhancing the radiosensitization effect of nano-hafnium oxide. In addition, in the special microenvironment of the tumor (such as high acidity, high hydrogen peroxide concentration, etc.), the highly active PtNPs with surface effects are oxidized and decomposed, releasing ionic platinum or related divalent platinum complexes that are toxic to cancer cells, producing a chemotherapeutic effect. Therefore, PtNPs, HfO 2-x @GQDs composite nanomaterials combine radiotherapy sensitization, improvement of tumor microenvironment and chemotherapy. It is a promising combined tumor treatment drug and is expected to achieve a combined treatment effect of radiotherapy-chemotherapy 1+1>2.

[0091] In the present application, the hafnium oxide / graphene quantum dot composite nanomaterial cannot decompose hydrogen peroxide, while the synthesized platinum particles / hafnium oxide / graphene quantum dot composite nanomaterial can quickly decompose hydrogen peroxide to form oxygen bubbles, indicating that the platinum nanoparticles in the material have a catalase effect, which can effectively improve the microenvironment of high concentration hydrogen peroxide and hypoxia in tumors, thereby enhancing the radiotherapy sensitization effect of the nanocomposite material. In addition, the hafnium oxide / graphene quantum dot composite nanomaterial has no cancer cell toxicity, while the synthesized platinum particles / hafnium oxide / graphene quantum dot composite nanomaterial has a chemotherapeutic effect. Therefore, the platinum particles / hafnium oxide / graphene quantum dot composite nanomaterial combines radiotherapy sensitization, improvement of tumor microenvironment, and chemotherapy, and is a drug for combined treatment of tumors with great application prospects.

[0092] The above are only a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application is disclosed as above with preferred embodiments, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial, It is characterized in that The composite nanomaterial includes platinum nanoparticles, nano-hafnium oxide and graphene quantum dots; The platinum nanoparticles and the hafnium oxide nanoparticles are dispersed in the graphene quantum dots; The graphene quantum dots are wrapped around the periphery of the platinum nanoparticles; The graphene quantum dots are wrapped around the periphery of the nano-hafnium oxide.

2. The platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to claim 1, It is characterized in that The mass percentage of the platinum nanoparticles in the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial is 10wt% to 15wt%.

3. The platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to claim 1, It is characterized in that The platinum nanoparticles in the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial have a (1 1 1) crystal plane, and the lattice spacing d is Preferably, all solutes in the aqueous solution of the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial pass through a microporous filter membrane with a pore size of 220 nm; Preferably, the water solubility of the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial is 80 to 250 mg / mL; The particle size of the platinum nanoparticles in the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial is 2-8 nm.

4. A method for preparing a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to any one of claims 1 to 3, It is characterized in that The following steps are involved: S1: Obtaining hafnium oxide / graphene quantum dot composite nanomaterials; S2: subjecting a mixture containing the hafnium oxide / graphene quantum dot composite nanomaterial and a platinum source to in-situ photoreduction to obtain a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial.

5. A method for preparing a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to claim 4, It is characterized in that In step S2, the mass ratio of the hafnium oxide / graphene quantum dot composite nanomaterial to the platinum source is 3 to 4:1; Preferably, the mixing ratio of the hafnium oxide / graphene quantum dot composite nanomaterial, the platinum source and the hole sacrificial agent is (1-1.5) g: (0.3-0.4) g: (15-25) mL.

6. A method for preparing a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to claim 4, It is characterized in that In step S2, the temperature of the in-situ photoreduction is -16°C to -10°C, and the illumination time is 1.5 to 2.5 hours; Preferably, the light source for the in-situ photoreduction is selected from near-ultraviolet light of a xenon lamp with a wavelength of 300 to 400 nm.

7. The method for preparing a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to claim 4, It is characterized in that In step S2, the platinum source is selected from at least one of sodium chloroplatinite, potassium chloroplatinite, ammonium chloroplatinite, platinum tetrachloride, chloroplatinic acid and sodium chloroplatinate.

8. The method for preparing a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to claim 4, It is characterized in that In step S2, the hole sacrificial agent for the in-situ photoreduction is a volatile organic solvent; preferably, the hole sacrificial agent is ethanol and / or methanol.

9. The method for preparing a platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to claim 4, It is characterized in that In step S2, the product after the in-situ photoreduction is further subjected to a purification process to obtain a purified composite nanomaterial; the purification process includes vacuum rotary evaporation, ultrafiltration, washing, and vacuum freeze-drying.

10. Use of the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial according to any one of claims 1 to 3 or the platinum particle / hafnium oxide / graphene quantum dot composite nanomaterial obtained by the preparation method according to any one of claims 4 to 9 in the preparation of anti-tumor drugs.

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