Bismuth selenide nanoparticles as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of nano materials and nano medicine, and particularly relates to bismuth selenide nano particles and a preparation method and application thereof.The bismuth selenide nano particles are prepared from sodium selenite, bismuth nitrate (III) pentahydrate, polyvinylpyrrolidone and hydrazine hydrate, polyvinylpyrrolidone is adsorbed on the surface of bismuth selenide generated by reaction of sodium selenite and bismuth (III) nitrate pentahydrate. After photo-thermal treatment is finished, ROS can be eliminated through the bismuth selenide nano-particles so as to reduce aseptic inflammation caused by postoperative infection, side effects caused by PTT are further reduced, and the bismuth selenide nano-particles are ideal materials for treating peritumoral infection caused by tumors.

Description

Technical Field

[0001] The present invention belongs to the technical fields of nanomaterials and nanomedicine, and particularly relates to a bismuth selenide nanoparticle, a preparation method thereof and an application thereof. Background Art

[0002] Nasopharyngeal carcinoma, with the English name Nasopharyngeal Carcinoma, abbreviated as NPC, is a squamous cell carcinoma originating from the pharyngeal recess. Nasopharyngeal carcinoma is highly sensitive to ionizing radiation, and radiotherapy is currently the preferred method for the treatment of nasopharyngeal carcinoma. However, the treatment difficulties of nasopharyngeal carcinoma lie in radiotherapy tolerance and distant metastasis. 10% - 20% of patients will experience local and / or lymph node recurrence after primary treatment because the radiation dose previously provided in the first course is usually close to the tolerance limit of surrounding normal structures, and the re-radiotherapy of locally recurrent NPC is challenging. The existing treatment means are limited. Therefore, it is crucial to explore new therapies for nasopharyngeal carcinoma.

[0003] Ferroptosis is a form of cell death dependent on iron and lipid peroxidation and has become a promising strategy in tumor treatment. Inducing ferroptosis requires a large amount of ROS accumulation and depletion of glutathione GSH. Bi 3+ can coordinate with GSH to further induce ferroptosis. P53-SLC7A11-GPX4 and P62-NRF2-GPX4 interact as classical pathways of ferroptosis. Bi 3+ After NIR irradiation, it increases the production of ROS, causes DNA damage, activates the wild-type p53 gene, down-regulates SLC7A11 to inhibit the input of cystine, and at the same time down-regulates P62-NRF2 to inhibit the reduction of GSSG to GSH. Bi 3+ also coordinates with GSH, jointly leading to the depletion of GSH, causing the inactivation of the intermediate product glutathione peroxidase 4, resulting in a large accumulation of LPO. On the other hand, it disrupts heavy chain ferritin 1, causing a decrease in iron storage capacity, and an increase in free Fe 2+ in cells, ultimately forming ferroptosis.

[0004] Apoptosis is a programmed cell death process and plays a crucial role in maintaining the intracellular environment stability. Mitochondria are important sites of apoptosis. Excessive ROS can induce the opening of the mitochondrial double membrane permeability pore, release apoptosis-related factors, and cause cell apoptosis. P62-NRF2-Caspase3 is a classical pathway of apoptosis. Photothermal synergistic Bi 3+ heating increases the level of oxidative stress, inhibits the antioxidant stress effect of the P62-NRF2 axis, and the accumulation of a large amount of ROS ultimately leads to apoptosis.

[0005] The aseptic inflammation associated with PTT involves multiple biological processes, including the release of pro-inflammatory cytokines, the aggregation of inflammatory cells, and the activated cell signaling pathways. Among the factors linking PTT and adverse inflammation, the production of reactive oxygen species is crucial for inflammation activation. Therefore, antioxidant strategies have been widely used in the treatment of acute and chronic inflammatory diseases. Infection, which is one of the main complications after tumor surgery clinically, is also a problem that troubles people.

[0006] In order to overcome the problem that photothermal therapy is prone to cause the residual of reactive oxygen species and trigger aseptic inflammation, there is an urgent need to provide a product that can be used to scavenge reactive oxygen species after the end of photothermal therapy. Summary of the Invention

[0007] In order to overcome the problem that photothermal therapy is prone to cause the residual of reactive oxygen species and trigger aseptic inflammation, the present invention provides bismuth selenide nanoparticles.

[0008] The technical solution adopted by the present invention is as follows:

[0009] The present invention provides bismuth selenide nanoparticles, which are made of sodium selenite, bismuth(III) nitrate pentahydrate, polyvinylpyrrolidone, and hydrazine hydrate. Among them, polyvinylpyrrolidone is adsorbed on the surface of bismuth selenide formed by the reaction of sodium selenite and bismuth(III) nitrate pentahydrate.

[0010] The present invention provides a preparation method of the bismuth selenide nanoparticles, including the following steps:

[0011] Dissolve sodium selenite, bismuth(III) nitrate pentahydrate, and polyvinylpyrrolidone in ethylene glycol. After mixing and heating, add hydrazine hydrate. Utilize the strong reducibility of hydrazine hydrate to reduce Se 4+ in sodium selenite to Se 2+ , and Se 2+ then reacts with Bi 3+ in bismuth(III) nitrate pentahydrate to generate bismuth selenide. Polyvinylpyrrolidone is adsorbed on the surface of bismuth selenide, and through steric hindrance effect and electrostatic interaction, the bismuth selenide nanoparticles are formed.

[0012] Preferably, the ratio of sodium selenite, bismuth(III) nitrate pentahydrate, polyvinylpyrrolidone, ethylene glycol, and hydrazine hydrate is 242 mg: 452 mg: 1 g: 105 mL: 2 mL.

[0013] Preferably, the temperature to be reached for heating is 180 °C.

[0014] Preferably, nitrogen is also used for airtightness to maintain a closed environment.

[0015] The present invention also provides an application of the bismuth selenide nanoparticles, and the bismuth selenide nanoparticles are used for preparing a preparation for treating nasopharyngeal carcinoma.

[0016] Preferably, the nasopharyngeal carcinoma further comprises nasopharyngeal carcinoma cells.

[0017] Preferably, the nasopharyngeal carcinoma cells comprise at least one of FAT, CNE1, and CNE2.

[0018] Preferably, the preparation further comprises a pharmaceutically acceptable excipient.

[0019] Preferably, the pharmaceutically acceptable excipient comprises at least one of a diluent, a disintegrant, a precipitation inhibitor, a glidant, a binder, a dispersant, a suspending agent, an isotonic agent, a thickening agent, an emulsifier, a preservative, and a stabilizer.

[0020] Preferably, the diluent comprises any one of starch, lactose, sucrose, and mannitol.

[0021] Preferably, the disintegrant comprises any one of starch, microcrystalline cellulose, and low-substituted hydroxypropyl cellulose.

[0022] Preferably, the precipitation inhibitor comprises any one of sodium dodecyl sulfate, Tween-80, polyvinylpyrrolidone, and hydroxypropyl methylcellulose.

[0023] Preferably, the glidant comprises any one of cationic polyacrylamide, poly(diallyldimethylammonium chloride), and cationic starch.

[0024] Preferably, the binder comprises any one of starch paste, hydroxypropyl methylcellulose, and polyvinylpyrrolidone.

[0025] Preferably, the dispersant comprises any one of sodium dodecyl sulfate, polyvinylpyrrolidone, and sodium carboxymethylcellulose.

[0026] Preferably, the suspending agent comprises any one of gum arabic, tragacanth, sodium carboxymethylcellulose, and hydroxypropyl methylcellulose.

[0027] Preferably, the isotonic agent comprises any one of sodium chloride, glucose, and mannitol.

[0028] Preferably, the thickening agent comprises any one of gum arabic, xanthan gum, and sodium carboxymethylcellulose.

[0029] Preferably, the emulsifier comprises any one of sodium dodecyl sulfate, benzalkonium chloride, and sorbitan fatty acid esters.

[0030] Preferably, the preservative comprises any one of benzoic acid, sorbic acid, methyl p-hydroxybenzoate, and benzalkonium bromide.

[0031] Preferably, any one of the stabilizers sodium sulfite, sodium bisulfite, tocopherol, and disodium ethylenediaminetetraacetate is included.

[0032] Preferably, the pharmaceutically acceptable dosage forms of the preparation include one of tablets, capsules, granules, injections, pills, powders, ointments, and oral liquids.

[0033] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0034] The present invention provides bismuth selenide nanoparticles, which are made of sodium selenite, bismuth(III) nitrate pentahydrate, polyvinylpyrrolidone, and hydrazine hydrate. Among them, polyvinylpyrrolidone is adsorbed on the surface of bismuth selenide formed by the reaction of sodium selenite and bismuth(III) nitrate pentahydrate. The present invention is prepared from polyvinylpyrrolidone, sodium selenite, and bismuth(III) nitrate pentahydrate. After the photothermal therapy, the bismuth selenide nanoparticles of the present invention can scavenge ROS to reduce the aseptic inflammation caused by postoperative infection, and further reduce the side effects brought by PTT. The bismuth selenide nanoparticles of the present invention are ideal materials for treating peritumoral infection caused by tumors. Selenium (Se), as an important trace element, is crucial for regulating the oxidation-antioxidation balance of the human body. Therefore, in the bismuth selenide nanoparticles of the present invention, supplementing selenium can prevent the accumulation of free radical substances and reduce cell damage.

[0035] The present invention has developed bismuth selenide nanoparticles based on NIR light irradiation for the treatment of nasopharyngeal carcinoma and postoperative anti-inflammatory. The photothermal properties of bismuth selenide nanoparticles are used as an active "switch", and the interaction of photothermal and photodynamic therapy under 808 nm laser irradiation generates a large amount of ROS. Ferroptosis and apoptosis of tumor cells are induced through classical pathways such as P53-SLC7A11-GPX4, P62-NRF2-FTH1, and p62-NRF2-caspase3, enhancing the anti-tumor effect. After the photothermal and photodynamic therapies, Bi 2 Se3 can scavenge the residual ROS, thereby protecting normal cells from inflammatory damage. This anti-tumor / postoperative anti-inflammatory integrated treatment strategy solves the problems of tumor treatment and postoperative complications. It provides a new way to solve the problems of tumor drug resistance and recurrence in clinical practice. This provides an innovative example for further studying the relevant mechanisms.

[0036] The nanoparticles prepared by the one-pot method of the present invention have good ROS generation performance and excellent synergistic ability of ferroptosis / apoptosis. Through further surface modification, the stability of the material is improved, and finally a new nanomaterial with good stability and biosafety is obtained for the photothermal / photodynamic / immune synergistic treatment of tumors.

[0037] In addition, compared with the prior art, the method for preparing two-dimensional metal nanomaterials using commercial polyvinylpyrrolidone, sodium selenite, and bismuth(III) nitrate pentahydrate provided by the present invention has the following outstanding advantages: the preparation method is simple, the raw materials are inexpensive, and large-scale preparation is possible; bismuth selenide nanoparticles are obtained by a one-pot method, the preparation method is extremely simple, and purification is convenient. Moreover, it can be dispersed and stabilized in an aqueous solution after simple surface modification; the prepared two-dimensional metal nanomaterials have good photothermal / photodynamic / immune synergistic therapeutic effects, very low cytotoxicity, and the potential for clinical translational application.

[0038] Due to the continuous development of nanotechnology, the combined treatment strategy of photothermal therapy and photodynamic therapy has been widely used in anti-tumor therapy. PDT utilizes the photosensitive properties of metal reagents to interact with light sources at specific wavelengths, release energy, and generate highly reactive singlet oxygen to kill or destroy diseased cells. PTT destroys tumor cells by generating local hyperthermia using a photothermal agent under near-infrared NIR irradiation. Bismuth-based materials are often used as photothermal agents and photosensitizers due to their good heat absorption and biosecurity.

[0039] In summary, an anti-tumor and anti-inflammatory two-in-one treatment strategy is formed through the "switch" of NIR. Through the synergy of PTT and PDT, the oxidative stress ability of Bi 2 Se3 induces ferroptosis and apoptosis to kill tumors. After tumor treatment, the bismuth selenide nanoparticles described in the present invention are used for postoperative anti-inflammatory to protect surrounding tissues from ROS damage, providing new ideas for the treatment of tumors by combining PTT and PDT. Brief Description of the Drawings

[0040] Figure 1 It is a schematic diagram of the method for preparing bismuth selenide nanoparticles and their potential biological mechanisms of the present invention. A: Schematic diagram of the synthesis in Example 1; B: Schematic diagram of the treatment of Bi 2 Se 3 NPs; C: Potential biological mechanisms in the presence of NTR; D: Biological mechanisms in the absence of NTR.

[0041] Figure 2 It is a material characterization diagram of bismuth selenide nanoparticles. A: XRD spectrum of Bi 2 Se 3 NPs; B: TEM image of Bi 2 Se 3 NPs; C: SAED diagram of Bi 2 Se 3 NPs; D: From left to right are bright field image, elemental mapping of bismuth, elemental mapping of selenium, and composite image of bismuth-selenium elemental mapping; E: From left to right are total spectrum, peak-fitting image of bismuth, and peak-fitting image of selenium.

[0042] Figure 3 Photothermal characterization of bismuth selenide nanoparticles. A: Heating curves at different powers; B: Heating curves at different concentrations; C: Thermal imaging images at different concentrations (left) and different powers (right); D: Heating curves of three thermal cycles; E: Heating curve of one thermal cycle; F: DPBF experiment; G: EPR experiment; H: 100 μg / mL Bi 2 Se 3 NPs' GSH clearance rate over time.

[0043] Figure 4 Evaluation of anti-tumor ability in vitro. A: Biosafety experiment of Bi 2 Se 3 NPs on HUVEC cells; B: CCK8 experiment of cytotoxicity of Bi 2 Se 3 NPs on FAT cells under NIR irradiation; C: Confocal evaluation of cellular Fe2 + level; D: Confocal evaluation of cell viability and death level; E: Confocal evaluation of cellular ROS production level; F: Confocal evaluation of changes in mitochondrial membrane potential; G: Confocal evaluation of cellular lipid peroxidation level; H: Flow cytometry experiment for apoptosis.

[0044] Figure 5 Study on the mechanism of tumor cell cytotoxicity. A: Schematic diagram of ferroptosis / apoptosis synergy; B: Hierarchical clustering analysis among different groups; C: Upregulation / downregulation analysis; D: WB experiment; E: KEGG enrichment pathway analysis; F: GO enrichment pathway analysis.

[0045] Figure 6 Evaluation of anti-tumor ability in vivo. A: Flow chart of subcutaneous xenograft tumors; B: Treatment thermal imaging; C: Physical tumor image; D: Tumor volume curve; E: Animal growth curve; F: H&E staining, left for control group and right for experimental group; G: Immunohistochemistry; H: Immunofluorescence.

[0046] Figure 7 Evaluation of anti-inflammatory ability in vitro. A: MB experiment of Bi 2 Se 3 NPs; B: SOD enzyme activity experiment; C: H 2 O 2 decomposition experiment; D: Dissolved oxygen experiment; E: Confocal evaluation of viability and death level; F: Confocal evaluation of ROS level; G: Confocal evaluation of mitochondrial membrane potential level.

[0047] Figure 8For the evaluation of in vivo anti-inflammatory ability. A: Schematic diagram of in vivo anti-inflammation; B - G are ELISA experiments for IL-6, IL-10, IL-1β, TNF-α, ATP, and MDA indicators in sequence; H: Results of ROS experiment; I: Detection results of IL-6; J: Detection results of IL-10 and L-1β.

[0048] Figure 9 For the evaluation of biosafety. A: Hemolysis experiment; B - L are detection results of HCT, HGB, MCHC, MCH, MCV, PDW, RBC, ALT, AST, BUN, and CR in sequence; M: HE staining of main organs. Detailed implementation manners

[0049] The present invention will be further described below through specific embodiments, but it does not limit the scope of the present invention. Without departing from the spirit and scope of the present invention, modifications or substitutions can be made to the details and forms of the technical solutions of the present invention, but these modifications or substitutions all fall within the protection scope of the present invention.

[0050] The inventive concept of the present invention is as follows:

[0051] The aseptic inflammation related to PTT involves multiple biological processes, including the release of pro-inflammatory cytokines, the aggregation and activation of inflammatory cells, and the activated cell signaling pathways. Among the factors connecting PTT and adverse inflammation, the generation of reactive oxygen species is crucial for inflammation activation. Therefore, antioxidant strategies have been widely used in the treatment of acute and chronic inflammatory diseases. Infection, as one of the main complications after tumor surgery clinically, is also a problem that troubles people.

[0052] In order to overcome the problem that photothermal therapy is prone to cause the residue of reactive oxygen species and trigger aseptic inflammation, there is an urgent need to provide a product that can be used to scavenge reactive oxygen species after the end of photothermal therapy.

[0053] Based on this, the present invention provides a bismuth selenide nanoparticle, which is made of sodium selenite, bismuth(III) nitrate pentahydrate, polyvinylpyrrolidone, and hydrazine hydrate. Among them, polyvinylpyrrolidone is adsorbed on the surface of bismuth selenide generated by the reaction of sodium selenite and bismuth(III) nitrate pentahydrate.

[0054] In order to enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below with specific embodiments. In the description of the present invention, unless otherwise specified, the reagents used are commercially available, and the methods used are conventional techniques in the art.

[0055] The abbreviation list of the present invention is shown in Table 1.

[0056] Table 1 Abbreviation list

[0057]

[0058]

[0059] Example 1

[0060] A method for preparing bismuth selenide nanoparticles is as follows:

[0061] First, a mixture of 242 mg of sodium selenite, 452 mg of bismuth(III) nitrate pentahydrate, and 1 g of polyvinylpyrrolidone PVP powder was dissolved in 105 mL of ethylene glycol and magnetically stirred for 30 minutes until completely dissolved. The resulting solution was placed in a three-necked flask and heated to 180 °C under nitrogen atmosphere. Immediately, 2 mL of 80% hydrazine hydrate solution was added, and the reactants darkened, indicating the synthesis. After 30 min, it was cooled to room temperature. Subsequently, it was centrifuged at 12,000 rpm for 10 min, and the black precipitate was washed three times with a mixed solution of acetone and deionized water, and then dried in a vacuum freeze dryer to obtain the bismuth selenide nanoparticles, denoted as Bi 2 Se3NPs, which is a single-crystalline nanodisk structure composed of Bi 2 Se3. The results are as Figure 1 shown.

[0062] Example 2

[0063] An application of bismuth selenide nanoparticles is as follows:

[0064] The Bi 2 Se 3 NPs prepared in Example 1 were characterized by transmission electron microscopy to obtain micrographs, SAED images, and elemental mapping images. The Zeta size and potential of the material were analyzed using a dynamic light scattering instrument. The phase structure of the material was detected by X-ray diffraction, i.e., XRD. The elements and valence states were measured by X-ray photoelectron spectroscopy XPS. The X-ray diffraction pattern was determined by an X-ray diffractometer. The results are as Figure 2 shown. Bi 2 Se 3 NPs were successfully synthesized and had good physical properties.

[0065] The Bi 2 Se 3 NPs prepared in Example 1 were configured into solutions with different concentrations. Under 808 nm near-infrared laser irradiation, the photothermal performance of Bi 2 Se 3 NPs was investigated at different concentrations and different powers. The generation of singlet oxygen was investigated using a DPBF probe and EPR experiment, and the glutathione peroxidase GSH-Px activity was investigated using a DTNB probe. The results are as Figure 3 shown. Bi 2 Se3 NPs have good photothermal and photosensitive properties.

[0066] Configure the Bi 2 Se 3 NPs in Example 1 into a solution with a concentration of 100 μg / mL, and co-culture the solution with HUVEC and FAT nasopharyngeal carcinoma cells respectively. After different treatments, perform cell viability and death experiments to verify the in vitro cytotoxicity of the material. The results are as Figure 4 shown, indicating that Bi 2 Se 3 NPs have good in vitro anti-tumor effects. Stain with Calcein-AM / PI, DCFH, JC-1, Liperfluo, FerroOrange, Propidium iodide / Annexin V-FITC probes respectively to observe the induction of cell viability and death, ROS production, mitochondrial membrane potential changes, lipid peroxidation, ferrous ion levels and apoptosis levels by the material, as Figure 4 shown. It is proved that NIR+Bi 2 Se 3 NPs have a synergistic anti-tumor effect of ferroptosis / apoptosis in vitro.

[0067] In order to determine the differences in overall gene expression between different treatment groups, the present invention performed total RNA sequencing on FAT cells. Treat the cells with different formulations, and extract the mRNA of each group of cells with TRIzol. The quantification, purification, reverse transcription and sequencing of mRNA were completed by Personalbio Co., Ltd. The number of fragments per kilobase of transcript FPKM was calculated as a normalized value to determine the gene expression level. Subsequently, KEGG and Gene Ontology GO enrichment analyses were performed to analyze the functional pathways related to DEGs, such as Figure 5 , and the results of the enrichment analysis showed that ferroptosis / apoptosis was up-regulated. WB electrophoresis experiments can verify ferroptosis / apoptosis-related proteins at the protein level, indicating the synergistic anti-tumor effect of ferroptosis / apoptosis.

[0068] In the figure, I: Control group; II: NIR group; III: NIR+Bi 2 Se 3 NPs group

[0069] Configure the Bi 2 Se 3 NPs prepared in Example 1 into a solution, inject it subcutaneously into tumor-bearing mice on the back for treatment, and the injection volume is 10 mg / kg. Use an infrared thermal imager to analyze the treatment process of different groups. The results are as Figure 6 shown, and immunohistochemistry and fluorescence staining of corresponding indicators are performed, indicating that NIR+Bi 2Se3NPs have good therapeutic effects on solid tumors.

[0070] Use the MB probe to verify the ability of Bi 2 Se 3 NPs to scavenge ROS, use SOD kits, CAT kits and dissolved oxygen experiments to verify the activities of SOD and CAT enzymes, and prove that Bi 2 Se 3 NPs have the ability to decompose residual H 2 O 2 after surgery and finally generate harmless H 2 O and O 2 . Stain with Calcein-AM / PI, DCFH, and JC-1 probes respectively to observe the cell viability and death, ROS production, and mitochondrial membrane potential changes induced by the material as Figure 7 shown. It was proved that Bi 2 Se 3 NPs have anti-inflammatory effects in vitro.

[0071] Inject the Bi 2 Se 3 NPs solution in Example 1 subcutaneously into tumor-bearing mice with lipopolysaccharide LPS on the back and perform treatment, and the injection volume is 10 mg / kg. The results are as Figure 8 shown. After treatment, blood was taken for detection by Elisa kit, and immunohistochemistry and fluorescence staining of corresponding indicators were performed, indicating that Bi 2 Se 3 NPs have good anti-inflammatory effects in vivo.

[0072] As Figure 9 , at 7 days or 14 days after injection, the mice were euthanized for H&E staining of major organs. At the same time, complete hematological and serum biochemical examinations were performed on the blood samples of the mice. In the serum biochemical examination, blood urea nitrogen BUN and creatinine CRE are two important indicators of renal function, and aspartate aminotransferase AST and alanine aminotransferase ALT are also important indicators of liver function. Other related blood parameters are as follows: lymphocyte LYM, mean platelet volume MPV, mean platelet volume MPV, mean corpuscular hemoglobin concentration MCHC, hemoglobin HGB, platelet distribution width PDW, mean corpuscular volume MCV, hematocrit HCT, white blood cell WBC, red blood cell RBC, and mean corpuscular hemoglobin MCH.

[0073] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope recorded in this specification.

[0074] The above-described embodiments merely represent several implementation manners of the present invention. The description thereof is relatively specific and detailed, but it should not be construed as a limitation to the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all fall within the protection scope of the present invention.

Claims

1. A bismuth selenide nanoparticle, characterized in that: The bismuth selenide nanoparticles are made of sodium selenite, bismuth (III) nitrate pentahydrate, polyvinyl pyrrolidone and hydrazine hydrate, wherein the polyvinyl pyrrolidone is adsorbed on the surface of bismuth selenide generated by the reaction of sodium selenite and bismuth (III) nitrate pentahydrate.

2. The method for preparing bismuth selenide nanoparticles according to claim 1, characterized in that: The following steps are involved: Sodium selenite, bismuth (III) nitrate pentahydrate and polyvinyl pyrrolidone are dissolved in ethylene glycol, mixed and heated, and then hydrazine hydrate is added to reduce the Se of sodium selenite by using the strong reducing property of hydrazine hydrate. 4+ Reduction to Se 2+ , Se 2+ Then with Bi in bismuth nitrate (III) pentahydrate 3+ The reaction generates bismuth selenide, and polyvinyl pyrrolidone is adsorbed on the surface of the bismuth selenide to form the bismuth selenide nanoparticles through steric hindrance effect and electrostatic action.

3. The preparation method according to claim 2, characterized in that: The ratio of the sodium selenite, bismuth (III) nitrate pentahydrate, polyvinyl pyrrolidone, ethylene glycol and hydrazine hydrate is 242 mg: 452 mg: 1 g: 105 mL: 2 mL.

4. The preparation method according to claim 2, characterized in that: The heating temperature should be 180°C.

5. The preparation method according to claim 2, characterized in that: During the heating, nitrogen is also required to be sealed to maintain a closed environment.

6. The use of bismuth selenide nanoparticles as claimed in claim 1, characterized in that: The bismuth selenide nanoparticles are used for preparing a preparation for treating nasopharyngeal carcinoma.

7. The use according to claim 6, characterized in that The nasopharyngeal carcinoma also includes nasopharyngeal carcinoma cells.

8. The use according to claim 7, characterized in that The nasopharyngeal carcinoma cells include at least one of FAT, CNE1 and CNE2.

9. The method according to claim 6, characterized in that The preparation also includes pharmaceutically acceptable excipients.

10. The method according to claim 9, characterized in that The pharmaceutically acceptable excipients include at least one of a diluent, a disintegrant, a precipitation inhibitor, a glidant, a binder, a dispersant, a suspending agent, an isotonic agent, a thickener, an emulsifier, a preservative and a stabilizer.

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