Hexagonal boron nitride nano-particles camouflaged by hybrid cell membrane as well as preparation method and application of hexagonal boron nitride nano-particles

Abstract

The invention discloses a hybrid cell membrane disguised hexagonal boron nitride nano-particle as well as a preparation method and application thereof, relates to the technical field of medicines, and aims to solve the problems of poor targeting property and biocompatibility of a boron carrying agent, insufficient in-vivo stability and tumor accumulation capacity of nano-particles and the like in BNCT tumor treatment in the prior art. The composite material comprises hexagonal boron nitride nanoparticles and a hybrid cell membrane coating the peripheries of the hexagonal boron nitride nanoparticles, and the hybrid cell membrane is formed by fusing a macrophage cell membrane and a tumor cell membrane. The targeting property and biocompatibility of the boron carrying agent and the in-vivo stability and tumor accumulation capacity of nanoparticles can be effectively enhanced, and the BNCT treatment effect of glioma is improved.

Description

Technical Field

[0001] The invention relates to a hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticle and a preparation method and application thereof, belonging to the technical field of medicine. Background Art

[0002] BNCT (boron neutron capture therapy) has gradually emerged as a cutting-edge cancer treatment method in recent years. Its principle is to first deliver boron-containing drugs into tumor cells, and then use neutron irradiation to cause nuclear reactions of boron elements. The released lithium-7 nuclei and alpha particles have high energy transfer line density and a short range, which is approximately equivalent to the diameter of a cell. Therefore, the energy released by these high-energy particles in tumor cells can effectively kill tumor cells, while causing relatively little damage to surrounding normal tissues, thereby achieving efficient and precise treatment of tumors.

[0003] However, BNCT faces many challenges in practical applications. One of the key issues is how to ensure that the boron carrier can be efficiently and specifically enriched in the tumor site while also having good biocompatibility to reduce damage to normal tissues.

[0004] At present, in the field of glioma treatment, research on boron carriers in BNCT has achieved certain results. For example, currently, small molecule compounds containing boron, such as borophenylalanine (BPA), are used clinically as boron carriers. However, such small molecule compounds have many limitations. First, they have a short half-life in the blood circulation, and it is often difficult to maintain effective drug concentrations for a long time. Secondly, due to the lack of specific recognition of tumor cells, their targeted enrichment effect at the tumor site is poor, and they cannot provide enough boron elements for BNCT, which seriously affects the treatment effect.

[0005] With the booming development of nanotechnology, many nanomaterials have been widely studied and explored for tumor treatment. Hexagonal boron nitride nanoparticles have become potential excellent drug carriers due to their excellent physical and chemical properties, such as high specific surface area, high boron content and chemical inertness. However, hexagonal boron nitride nanoparticles have shortcomings in terms of stability, blood circulation time and targeting in vivo, which limits their application effect in tumor treatment.

[0006] In summary, the existing technologies in BNCT treatment of gliomas have shortcomings such as poor targeting and biocompatibility of boron carriers, insufficient in vivo stability of nanoparticles and insufficient tumor accumulation ability. Summary of the invention

[0007] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticle and its preparation method and application, which can effectively enhance the targeting and biocompatibility of the boron carrier, the in vivo stability and tumor accumulation ability of the nanoparticles, and improve the BNCT treatment effect of glioma.

[0008] To achieve the above object, the present invention is implemented by adopting the following technical solutions: In a first aspect, the present invention provides a hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticle, comprising a hexagonal boron nitride nanoparticle and a hybrid cell membrane coated on the periphery of the hexagonal boron nitride nanoparticle, wherein the hybrid cell membrane is formed by the fusion of a macrophage membrane and a tumor cell membrane.

[0009] Optionally, the particle size of the hexagonal boron nitride nanoparticles is within 100 nm, the hexagonal boron nitride nanoparticles are distributed in ultrapure water in the form of nanoparticles, and the concentration of the boron element in the ultrapure water is in the range of 0.1-10 mg / mL.

[0010] Optionally, the mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles is 1:0.1-10; and / or, the mass ratio of the macrophage membrane to the tumor cell membrane in the hybrid cell membrane is 1:0.1-10.

[0011] In a second aspect, the present invention further provides a method for preparing the hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles as described in any one of the above, comprising: Extraction of macrophage and tumor cell membranes; The macrophage membrane and the tumor cell membrane are mixed and subjected to ultrasonic treatment to obtain a hybrid cell membrane; The hybrid cell membrane is mixed with hexagonal boron nitride nanoparticles, and then subjected to ultrasonic treatment to obtain hexagonal boron nitride nanoparticles coated with the hybrid membrane; The redundant hybrid cell membrane in the hybrid membrane-coated hexagonal boron nitride nanoparticles is removed to obtain the hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles.

[0012] Furthermore, the extraction of macrophage membranes and tumor cell membranes comprises: Cultivating RAW264.7 cell line and GL261 cell line, wherein the RAW264.7 cell line is used for macrophage cell membrane, and the GL261 cell line is used for extracting tumor cell membrane; The GL261 cell line and the RAW264.7 cell line were centrifuged a, and then a membrane protein extraction buffer was added, and the cells were placed in an ice bath, and then the cells were fully lysed by homogenization. After centrifugation b, the supernatant was collected, and the supernatant was centrifuged again c, and then the precipitate was collected; The precipitate was resuspended in ultrapure water, centrifuged for d, and the precipitate was taken out, and after washing, macrophage membrane precipitate and tumor cell membrane precipitate were obtained respectively; The macrophage membrane precipitate and tumor cell membrane precipitate were resuspended with ultrapure water and stored in a refrigerator.

[0013] Furthermore, the amount of membrane protein extraction buffer added is 1 mL for every 20 to 40 million cells.

[0014] Furthermore, the centrifugation treatment a is centrifugation at 500-800 rpm for 1-5 minutes, taking the precipitate and washing it, then resuspending the precipitate with PBS, and then centrifuging it at 500-800 rpm for 1-5 minutes, repeating 2-3 times; the centrifugation treatment b is centrifugation at 2000-3000 rpm for 15-20 minutes; the centrifugation treatment c and the centrifugation treatment d are both centrifugation at 13000-15000 rpm for 25-35 minutes.

[0015] Furthermore, the ultrasonic treatment a includes ultrasonic treatment at a power of 60-90 W for 5-10 minutes in an ice bath environment; the ultrasonic treatment b includes ultrasonic treatment at a power of 60-90 W for 0.5-1 hour in an ice bath environment, and shaking the ultrasonic treatment at intervals during the ultrasonic treatment.

[0016] Furthermore, the method of removing redundant hybrid cell membranes from hybrid membrane-coated hexagonal boron nitride nanoparticles to obtain hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles comprises: The hybrid membrane-coated hexagonal boron nitride nanoparticles were transferred to a centrifuge tube and centrifuged at 3000-6000 rpm for 8-12 minutes to obtain the precipitate; Resuspend the pellet in ultrapure water and store in refrigerator.

[0017] In a third aspect, the present invention provides a drug for treating glioma by boron neutron capture, comprising any of the hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles described above.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The present invention uses hexagonal boron nitride nanoparticles as a boron carrier, which overcomes the defects of using a simple boron-containing small molecule compound as a boron carrier, significantly prolongs the half-life of the boron carrier in the blood circulation, can maintain an effective drug concentration for a long time, has a good tumor targeting enrichment effect, and provides a continuous and stable supply of boron elements for BNCT, thereby improving the treatment effect; The present invention uses a hybrid cell membrane formed by the fusion of macrophage membrane and tumor cell membrane to coat hexagonal boron nitride nanoparticles, so that the nanoparticles can more effectively penetrate tumor tissue, improve the uniformity of drug distribution inside the tumor, enhance the in vivo stability of the nanoparticles, improve the surface specificity, and be easily recognized by tumor cells, which greatly improves the targeted enrichment ability of the nanoparticles for glioma cells, ensuring that more boron elements accurately reach the tumor site and achieve effective accumulation at the tumor site; Compared with single tumor cell membrane, the hybrid cell membrane used in the present invention can increase the circulation time of nanoparticles in the body, accurately target tumors to improve tumor targeting efficiency, and effectively enrich the nanoparticles in the glioma part; The hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles of the present invention effectively reduce the immunogenicity of the nanoparticles, reduce the risk of being cleared by the immune system, prolong their circulation time in the body, and significantly reduce side effects such as immune responses induced by the nanoparticles, thereby improving the safety of treatment and the tolerance of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a TEM schematic diagram of the hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles (GM / h-BN) in Example 1 of the present invention, wherein the left side is under a 100 nm scale and the right side is under a 50 nm scale; Figure 2 Schematic diagram of particle size distribution of hexagonal boron nitride nanoparticles camouflaged by hybrid cell membranes in Example 1 of the present invention; Figure 3 It is a schematic diagram comparing the particle size and Zeta potential of the hybrid cell membrane camouflaged hexagonal boron nitride nanoparticles (GM / h-BN) and hexagonal boron nitride nanoparticles (h-BN) in Example 1 of the present invention, wherein the left side is a schematic diagram for particle size comparison, and the right side is a schematic diagram for Zeta potential comparison; Figure 4 It is a schematic diagram of the comparison of FTIR infrared spectra of the hybrid cell membrane camouflaged hexagonal boron nitride nanoparticles (GM / h-BN), hexagonal boron nitride nanoparticles (h-BN), and the hybrid cell membrane (GM) in Example 1 of the present invention; Figure 5 Schematic diagram of the particle size change trend of the hybrid cell membrane camouflaged hexagonal boron nitride nanoparticles (GM / h-BN) within 2 weeks in Example 1 of the present invention. DETAILED DESCRIPTION

[0020] The present invention will be further described below in conjunction with the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and cannot be used to limit the protection scope of the present invention. Example 1

[0021] The embodiment of the present invention provides a method for preparing hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles, comprising the following steps: 1. Cell membrane extraction 1. Cell culture: The culture medium used was DMEM high-glucose medium containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin.

[0022] Culture conditions: GL261 cell line and RAW264.7 cell line were cultured in an incubator at 37°C and 5% CO2.

[0023] When the cells were cultured to about 90% confluence in the culture dish, the cell membrane extraction operation was started.

[0024] 2. Cell membrane extraction: Tumor cell membranes were extracted from the GL261 cell line, and macrophage membranes were extracted from the RAW264.7 cell line. The specific cell membrane extraction steps include: First, collect the cells, centrifuge at 800 rpm for 5 minutes, and carefully discard the supernatant. Then wash the cells, resuspend the cell pellet in 2 ml PBS, and centrifuge at 800 rpm for 5 minutes. Repeat this process 2-3 times.

[0025] Next, add an appropriate amount of membrane protein extraction buffer containing PMSF (1 ml per 30 million cells) and incubate on ice for 15 minutes.

[0026] Afterwards, the cells were transferred to a 5 ml glass homogenizer and manually homogenized 30 times to fully lyse the cells.

[0027] Transfer the lysate to a 1.5 ml centrifuge tube, centrifuge at 3000 rpm for 15 minutes, and take the supernatant. Centrifuge the supernatant at 14000 rpm for 30 minutes, collect the precipitate, which is the cell membrane. Then resuspend the cell membrane precipitate with ultrapure water, centrifuge at 14000 rpm for 30 minutes, and take the washed cell membrane precipitate.

[0028] Finally, the cell membrane pellet was resuspended with 100 ul of ultrapure water and stored in a 4°C refrigerator for later use.

[0029] 2. Preparation of hybrid cell membrane (GM) Accurately measure macrophage cell membranes and tumor cell membranes at a mass ratio of 1:1 and place them in a 1.5 mL centrifuge tube.

[0030] The centrifuge tube was placed in an ice bath and an ultrasonic cleaner was used. The ultrasonic power was set to 60 W and the ultrasonic time was set to 5 minutes. The two cell membranes were fully mixed by ultrasonic treatment to form a hybrid cell membrane.

[0031] 3. Hybrid cell membrane coated with hexagonal boron nitride (GM / h-BN) Weigh 2 mL of hexagonal boron nitride nanoparticles (h-BN) with a boron concentration of 0.5 mg / mL, add it to the hybrid membrane solution containing about 1 mg of membrane protein, and mix thoroughly to ensure that the hybrid cell membrane is in full contact with the hexagonal boron nitride nanoparticles to obtain a mixed system, that is, the mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles in this embodiment is 1:1.

[0032] The mixed system was transferred to a 10 mL glass vial, placed in an ultrasonic cleaner, and subjected to ultrasonic treatment for 1 hour at a power of 60 W in an ice bath. During the ultrasonic process, the vial was gently shaken every 10 minutes to allow the hybrid film to be evenly coated on the surface of the hexagonal boron nitride nanoparticles to achieve the desired coating effect.

[0033] 4. Purification of samples The hybrid membrane-coated hexagonal boron nitride solution was transferred to a centrifuge tube and centrifuged at 6000 rpm for 10 minutes.

[0034] Carefully remove the supernatant, collect the precipitate, and then resuspend the precipitate with 2 mL of ultrapure water to fully remove excess cell membrane and obtain relatively pure hybrid membrane-coated hexagonal boron nitride nanoparticles. Finally, store the purified hybrid membrane-coated hexagonal boron nitride nanoparticle solution in a 4°C refrigerator for later use. Example 2

[0035] The only difference between this embodiment and embodiment 1 is that 4 mL of hexagonal boron nitride nanoparticles (h-BN) with a boron concentration of 0.5 mg / mL is weighed and added to a hybrid membrane solution containing about 1 mg of membrane protein, that is, the mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles in this embodiment is 1:2. Example 3

[0036] The only difference between this embodiment and embodiment 1 is that 8 mL of hexagonal boron nitride nanoparticles (h-BN) with a boron concentration of 0.5 mg / mL are weighed and added to a hybrid membrane solution containing about 1 mg of membrane protein, that is, the mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles in this embodiment is 1:4.

[0037] The hybrid cell membrane (GM), hexagonal boron nitride nanoparticles (h-BN), and hexagonal boron nitride nanoparticles coated with the hybrid membrane (GM / h-BN) obtained in Example 1 were subjected to property analysis.

[0038] 1. Electron microscopic observation of hexagonal boron nitride nanoparticles coated with hybrid membranes, such as Figure 1As shown, it can be clearly seen that the nanomaterial presents a regular disc-shaped structure. The TEM image clearly shows a typical "core-shell structure". The hybrid film coated on the surface has a uniform thickness of about 5nm and fits tightly to the surface of the nanoparticles without obvious wrinkles or peeling. It provides structural support for the realization of nanoparticle functions. This uniform and tight coating structure helps to protect the core of the nanoparticles, enhance their stability in complex biological environments, reduce nonspecific interactions with non-target tissues, and provide a structural basis for precise drug delivery.

[0039] 2. DLS test was performed on the hybrid membrane-coated hexagonal boron nitride nanoparticles. The results of the three repeated tests were as follows: Figure 2 and Figure 3 As shown in the figure, the hydrated particle size of the hybrid membrane-coated boron nitride nanomaterials is distributed in the range of 25 ~170 nm, with an average particle size of 59.14 nm, a polydispersity index (PDI) of 0.224, and a Zeta potential of -30.6mV. The particle size and Zeta potential are significantly changed compared with hexagonal boron nitride nanoparticles. The change in particle size is suitable for in vivo circulation and tumor penetration. The Zeta potential optimization enhances colloidal stability, prevents aggregation and precipitation, and improves storage and application stability. Compared with uncoated boron nitride nanoparticles, the particle size has increased and the distribution is more concentrated, which is attributed to the successful coating of the hybrid membrane. The stable particle size and low PDI indicate that the nanomaterial has good dispersibility in the solution and low tendency to agglomerate, which is conducive to long-term stable existence in the blood circulation after intravenous injection, increasing the probability of accumulation in the tumor site and improving the therapeutic effect.

[0040] 3. Infrared spectroscopy analysis of hybrid membrane-coated hexagonal boron nitride nanoparticles, such as Figure 4 As shown, the characteristic peaks of GM and h-BN are completely retained in GM / h-BN, indicating that the coating does not damage the chemical structure of the material, maintains the original physicochemical properties while imparting biological functions.

[0041] 4. The protein concentration was accurately measured using the BCA method. The result showed that the protein concentration of the hybrid membrane-coated hexagonal boron nitride nanoparticles was 0.196 mg / ml. This concentration data confirmed that when the cell membrane successfully coated the hexagonal boron nitride nanoparticles, the membrane protein was also retained, thus laying a solid foundation for the targeting function of the nanoparticles and greatly enhancing their application potential and value in the field of tumor treatment.

[0042] 5. Long-term monitoring of the particle size variation trend of hybrid membrane-coated hexagonal boron nitride nanoparticles, such as Figure 5 As shown, the particle size of the nanoparticles basically does not change over time, indicating that the material has good storage and application stability, is resistant to complex environments and long-term storage, and is suitable for clinical transformation.

[0043] The following is a comparative analysis of Examples 1 to 3: The DLS test was performed on Examples 2 and 3 in the same manner as in Example 1, and the results were as follows: In Example 2, when the mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles is set to 1:2, the prepared hybrid membrane-coated boron nitride nanomaterial has a hydrated particle size distribution in the range of 20 to 400 nm, an average particle size of 66.93 nm, a polydispersity index (PDI) of 0.203, and a Zeta potential measurement value of -0.262 mV. In Example 3, when the mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles is adjusted to 1:4, the corresponding hybrid membrane-coated boron nitride nanomaterial has a hydrated particle size distribution in the range of 20 to 350 nm, an average particle size of 73.27 nm, a polydispersity index (PDI) of 0.217, and a Zeta potential of -0.225 mV.

[0044] The difference between Example 1 and Examples 2 and 3 is mainly that the mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles is different. In Example 1, the mass ratio is 1:1, in Example 2 it is 1:2, and in Example 3 it is 1:4.

[0045] Therefore, it can be concluded that compared with Examples 2 and 3, Example 1 has the following advantages: (1) The particle size distribution is narrower in terms of particle size and dispersion coefficient: The hydrated particle size of the boron nitride nanomaterial coated with the hybrid membrane in Example 1 is distributed in the range of 25 to 170 nm, that in Example 2 is in the range of 20 to 400 nm, and that in Example 3 is in the range of 20 to 350 nm. By comparison, it can be seen that the particle size distribution of Example 1 is relatively narrower, which means that its particle size is more uniform and may exhibit more stable and predictable behavior during in vivo circulation and drug delivery.

[0046] Smaller average particle size: The average particle size of Example 1 is 59.14 nm, which is smaller than 66.93 nm of Example 2 and 73.27 nm of Example 3. Smaller particle size is conducive to the penetration and diffusion of nanoparticles in the body, and is easier to penetrate tissue and cell barriers, thereby increasing the probability of accumulation at the tumor site and improving the therapeutic effect.

[0047] (2) Zeta potential has a larger absolute value: the Zeta potential in Example 1 is -30.6 mV, which is greater than -0.262 mV in Example 2 and -0.225 mV in Example 3. The larger the absolute value of the Zeta potential, the higher the surface charge density of the nanoparticles and the stronger the electrostatic repulsion, thereby enhancing the colloidal stability and more effectively preventing aggregation and precipitation, which is beneficial to improving the stability of the nanoparticles during storage and application, and ensuring the quality and efficacy of the drug preparation.

[0048] The characteristics of Example 1 in terms of particle size and Zeta potential related data may enable it to have better performance in terms of in vivo circulation, tumor targeted enrichment, drug stability, etc., and is more suitable as a drug carrier for boron neutron capture therapy for glioma, and is expected to improve the treatment effect and safety.

[0049] In summary, the optimal mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles in this patent is 1:1.

[0050] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticle, characterized in that: The invention comprises hexagonal boron nitride nanoparticles and a hybrid cell membrane coated on the periphery of the hexagonal boron nitride nanoparticles, wherein the hybrid cell membrane is formed by the fusion of a macrophage cell membrane and a tumor cell membrane.

2. The hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to claim 1, characterized in that: The particle size of the hexagonal boron nitride nanoparticles is within 100 nm. The hexagonal boron nitride nanoparticles are distributed in ultrapure water in the form of nanoparticles. The concentration of the boron element in the ultrapure water is in the range of 0.1-10 mg / mL.

3. The hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to claim 1, characterized in that: The mass ratio of the hybrid cell membrane to the hexagonal boron nitride nanoparticles is 1:0.1-10; and / or the mass ratio of the macrophage membrane to the tumor cell membrane in the hybrid cell membrane is 1:0.1-10.

4. A method for preparing hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to any one of claims 1 to 3, characterized in that: include: Extraction of macrophage and tumor cell membranes; The macrophage membrane and the tumor cell membrane are mixed and subjected to ultrasonic treatment to obtain a hybrid cell membrane; The hybrid cell membrane is mixed with hexagonal boron nitride nanoparticles, and then subjected to ultrasonic treatment to obtain hexagonal boron nitride nanoparticles coated with the hybrid membrane; The redundant hybrid cell membrane in the hybrid membrane-coated hexagonal boron nitride nanoparticles is removed to obtain the hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles.

5. The method for preparing hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to claim 4, characterized in that: The method of extracting macrophage membranes and tumor cell membranes comprises: Cultivating RAW264.7 cell line and GL261 cell line, wherein the RAW264.7 cell line is used for macrophage cell membrane, and the GL261 cell line is used for extracting tumor cell membrane; The GL261 cell line and the RAW264.7 cell line were centrifuged a, and then a membrane protein extraction buffer was added, and the cells were placed in an ice bath, and then the cells were fully lysed by homogenization. After centrifugation b, the supernatant was collected, and the supernatant was centrifuged again c, and then the precipitate was collected; The precipitate was resuspended in ultrapure water, centrifuged for d, and the precipitate was taken out, and after washing, macrophage membrane precipitate and tumor cell membrane precipitate were obtained respectively; The macrophage membrane precipitate and tumor cell membrane precipitate were resuspended with ultrapure water and stored in a refrigerator.

6. The method for preparing hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to claim 5, characterized in that: The amount of membrane protein extraction buffer added is 1 mL for every 20 to 40 million cells.

7. The method for preparing hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to claim 5, characterized in that: The centrifugation treatment a is centrifugation at 500-800 rpm for 1-5 minutes, taking the precipitate and washing it, then resuspending the precipitate with PBS, and then centrifuging it at 500-800 rpm for 1-5 minutes, repeating 2-3 times; the centrifugation treatment b is centrifugation at 2000-3000 rpm for 15-20 minutes; the centrifugation treatment c and the centrifugation treatment d are both centrifugation at 13000-15000 rpm for 25-35 minutes.

8. The method for preparing hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to claim 4, characterized in that: The ultrasonic treatment a comprises ultrasonic treatment at a power of 60-90 W for 5-10 minutes in an ice bath environment; the ultrasonic treatment b comprises ultrasonic treatment at a power of 60-90 W for 0.5-1 hour in an ice bath environment, and shaking the ultrasonic treatment at intervals during the ultrasonic treatment.

9. The method for preparing hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles according to claim 4, characterized in that: The method of removing redundant hybrid cell membranes from hybrid membrane-coated hexagonal boron nitride nanoparticles to obtain hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles comprises: The hybrid membrane-coated hexagonal boron nitride nanoparticles were transferred to a centrifuge tube and centrifuged at 3000-6000 rpm for 8-12 minutes to obtain the precipitate; Resuspend the pellet in ultrapure water and store in refrigerator.

10. A drug for treating glioma by boron neutron capture, characterized in that: It comprises the hybrid cell membrane-camouflaged hexagonal boron nitride nanoparticles as described in any one of claims 1 to 3.

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