Bionic nanoparticle as well as preparation method and application thereof

Abstract

The invention provides a bionic nanoparticle and a preparation method and application thereof, and belongs to the field of biomedicine.The bionic nanoparticle comprises a shell and an anti-cancer medicine.The shell is obtained by fusing phospholipid bilayers and a tumor biofilm-target recognition agent conjugate, the anti-cancer medicine is distributed between the phospholipid bilayers and in a shell cavity, and the tumor biofilm-target recognition agent conjugate is formed by fusing the phospholipid bilayers and the tumor biofilm-target recognition agent conjugate. The target spot recognition agent is combined with the outer side of the tumor biological membrane. The bionic nanoparticle provided by the invention has excellent targeting performance, has an effect of resisting tumor cell escape and can assist T cells in killing tumor cells, and meanwhile, the anti-cancer drug carried by the bionic nanoparticle can also promote tumor cell apoptosis, so that the bionic nanoparticle has an excellent application prospect.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to a bionic nanoparticle and a preparation method and application thereof. Background Art

[0002] Immunotherapy is an important treatment option to improve the survival rate of lung cancer patients. Some patients respond well to immunotherapy and their survival time is significantly prolonged, but immunotherapy drugs have little effect on other patients. The reason is that PD-L1 on cancer cells binds to PD-1 on T cells, inhibiting T cell proliferation and the secretion of life-killing interferon-γ (IFN-γ), interleukin-2 (IL-2), etc., promoting cancer immune escape, which will reduce the efficacy of immunotherapy. Immunotherapy drugs developed based on this mechanism can induce a lasting anti-tumor response. For example, atezolizumab is a humanized PD-L1 blocker that can bind to PD-L1 on tumor cells and block its interaction with T cells and antigen-presenting cells PD-1, thereby relieving PD-1 / PD-L1-mediated immunosuppression and promoting T cells to attack tumor cells. Atezolizumab treatment doubles the patient's overall survival, improves the quality of life, and has a good safety profile. However, there are still a considerable number of patients who cannot benefit from it. Therefore, another idea of ​​blocking PD-L1 / PD-1 binding was born, that is, reducing PD-L1 in tumor cells or reducing the expression of PD-1 on T cells. However, most of the research in this field is still in the field of gene regulation of PD-L1 / PD-1 degradation, such as benzosceptrin C, which induces lysosomal degradation of PD-L1 or PD-1 and inhibits anti-tumor immune escape. However, these new drugs are still a long way from clinical use. Summary of the invention

[0003] The technical problem to be solved by the present invention is how to inhibit the immune escape of tumor cells and improve the targeting performance of immune preparations. Based on this, the present invention provides a bionic nanoparticle and a preparation method and application thereof.

[0004] The first aspect of the present invention provides a biomimetic nanoparticle, which includes a shell and an anticancer drug, wherein the shell is obtained by fusion of a phospholipid bilayer and a tumor biomembrane-target recognition agent conjugate, the anticancer drug is distributed between the phospholipid bilayers and in the shell cavity, and the target recognition agent is bound to the outside of the tumor biomembrane.

[0005] In the bionic nanoparticles provided by the present invention, the shell is composed of a phospholipid bilayer, a tumor biomembrane, and a target recognition agent. Among them, the tumor biomembrane improves the biocompatibility of the bionic nanoparticles. The present invention hybridizes the tumor cell membrane with the drug-loaded liposome, which can not only increase the biocompatibility of the nanoparticles, but also greatly improve the tumor targeting ability of the nanoparticles. The target recognition agent is used to transport the bionic nanoparticles to the location where the tumor occurs.

[0006] Preferably, the anticancer drug is selected from any one or more of artemisinin, dihydroartemisinin, artesunate, artemether, carboplatin, mitomycin, exotecan, cisplatin, vinorelbine, paclitaxel, docetaxel, vinblastine, pemetrexed, bevacizumab, gefitinib, erlotinib, icotinib, osimertinib, recombinant human endostatin, and nivolumab.

[0007] Preferably, the target recognition agent is an antibody against PD-1 or any other cancer cell-specific membrane protein.

[0008] When the target recognition agent is PD-1, PD-1 binds to PD-L1 of tumor cells, relieving PD-1 / PD-L1-mediated immunosuppression and allowing T cells to kill tumor cells.

[0009] Preferably, the phospholipid bilayer comprises phospholipids and cholesterol, wherein the phospholipids are selected from any one or more of soybean lecithin, hydrogenated soybean lecithin, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoyl lecithin, dimyristoylphosphatidylcholine, 1-palmitoyl-2-oleoyl lecithin, lauroyl lecithin, dimyristoyl lecithin, dilauroyl phosphatidylglycerol, dipalmitoylphosphatidic acid, dimyristoylphosphatidylethanolamine, dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylserine, dipalmitoylphosphatidyldiserine, brain phosphatidylserine, brain sphingomyelin, dipalmitoyl sphingomyelin, distearoyl sphingomyelin, and distearoylphosphatidylethanolamine.

[0010] Preferably, the mass proportion of cholesterol in the phospholipid bilayer is 6-10%.

[0011] Preferably, the anticancer drug accounts for 5% to 15% by mass in the bionic nanoparticles.

[0012] The second aspect of the present invention provides a method for preparing the aforementioned bionic nanoparticles, which specifically comprises the following steps: S1: combining the target recognition agent with the tumor biofilm to obtain the target recognition agent-TM; S2: dissolving phospholipids, cholesterol and anticancer drugs in an organic solvent, removing the organic solvent after mixing, obtaining a film, hydrating the film and mechanically dispersing it to obtain drug-loaded liposomes; S3: Drug-loaded liposomes and target recognition agent-TM were mixed and biomimetic nanoparticles were prepared using extrusion method.

[0013] The present invention provides an application of the aforementioned bionic nanoparticles, which includes: using the bionic nanoparticles to prepare drugs and / or diagnostic reagents for treating lung cancer.

[0014] Preferably, the lung cancer is non-small cell lung cancer.

[0015] Compared with the prior art, the present invention has the following beneficial effects: in the bionic nanoparticles provided by the present invention, the target recognition agent is used to transport the bionic nanoparticles to the tumor site. After the bionic nanoparticles arrive at the site, the bionic nanoparticles are taken into the tumor cells through the endocytosis of the tumor cells and release anticancer drugs in the tumor cells, thereby achieving the purpose of killing the tumor cells. The use of the bionic nanoparticles provided by the present invention can effectively achieve the purpose of anti-tumor cell escape at the same time. In summary, the bionic nanoparticles provided by the present invention provide a new strategy for the treatment of non-small cell lung cancer in terms of therapeutic potential and mechanism of action. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 A schematic diagram of the mechanism of action of biomimetic nanoparticles provided in a specific embodiment of the present invention; Figure 2 Characterization results of biomimetic nanoparticles provided for specific embodiments of the present invention; Figure 3 Results of the uptake of biomimetic nanoparticles by cancer cells provided in a specific embodiment of the present invention; Figure 4 The experimental results of the targeting of the bionic nanoparticles provided in the specific embodiment of the present invention are verified by in vitro experiments. DETAILED DESCRIPTION

[0017] In order to make the above-mentioned purposes, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below. It should be noted that the following embodiments are only used to illustrate the implementation method and typical parameters of the present invention, and are not used to limit the parameter range described in the present invention. Reasonable changes derived therefrom are still within the scope of protection of the claims of the present invention.

[0018] It should be noted that the endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed in this article.

[0019] Unless otherwise defined, all terms, symbols and other scientific terms used herein are intended to have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. In some cases, terms with conventionally understood meanings are defined herein for the purpose of clarification or ease of reference, and such definitions herein should not be construed as indicating significant differences from conventional understandings in the art. The technical methods described or cited herein are generally well understood by those skilled in the art and are adopted by conventional methods. Unless otherwise stated, the use of commercially available kits, reagents and instruments is carried out in accordance with the protocols and parameters given by the manufacturer.

[0020] Existing tumor immunotherapy drugs often have the defects of large side effects, poor therapeutic effects and poor prognosis. Based on this, a specific embodiment of the present invention provides a bionic nanoparticle, which includes a shell and an anticancer drug, wherein the shell is obtained by fusion of a phospholipid bilayer and a tumor biomembrane-target recognition agent conjugate, the anticancer drug is distributed between the phospholipid bilayers and in the shell cavity, and the target recognition agent is bound to the outside of the tumor biomembrane.

[0021] In the bionic nanoparticles provided by the present invention, the shell is composed of a phospholipid bilayer, a tumor biomembrane, and a target recognition agent, wherein the tumor biomembrane improves the biocompatibility of the bionic nanoparticles, and the target recognition agent is used to transport the bionic nanoparticles to the location where the tumor occurs.

[0022] In the above embodiment, the target recognition agent can be selected as PD-1 or any cancer cell-specific membrane protein antibody. When the target recognition agent is a membrane protein antibody specific to the relevant cancer cells, the bionic nanoparticles provided in the specific embodiment of the present invention can be targeted and delivered to the tumor occurrence site through the relevant antibodies. When the target recognition agent is PD-1, the bionic nanoparticles not only have the advantage of high performance in anti-tumor cell escape, but also can bind to the PD-L1 of tumor cells and block its interaction with T cells and antigen-presenting cell PD-1, thereby relieving PD-1 / PD-L1-mediated immunosuppression, promoting T cells to attack tumor cells, and improving the treatment effect.

[0023] In the above embodiment, the phospholipid bilayer includes phospholipids and cholesterol, wherein the phospholipids are selected from any one or more of soybean lecithin, hydrogenated soybean lecithin, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoyl lecithin, dimyristoylphosphatidylcholine, 1-palmitoyl-2-oleoyl lecithin, lauroyl lecithin, dimyristoyl lecithin, dilauroyl phosphatidylglycerol, dipalmitoylphosphatidic acid, dimyristoylphosphatidylethanolamine, dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylserine, dipalmitoylphosphatidyldiserine, brain phosphatidylserine, brain sphingomyelin, dipalmitoyl sphingomyelin, distearoyl sphingomyelin, and distearoylphosphatidylethanolamine.

[0024] In the above embodiment, the mass proportion of cholesterol in the phospholipid bilayer is 6-10%.

[0025] In the above embodiment, the mass proportion of the anticancer drug in the bionic nanoparticles is 5% to 15%.

[0026] Phospholipids and cholesterol are the main molecules for constructing artificial cell membranes and the main components of the plasma membranes of almost all known organisms. In water, they can spontaneously self-assemble into spherical vesicles (liposomes) with double-layer membranes. Due to the encapsulation ability of hydrophobic and hydrophilic drugs, good physical and chemical control, limited toxicity, biocompatibility and biodegradability, however, liposomes lack the complex antigens on natural cell membranes and cannot actively home to disease sites or cells. Therefore, the specific embodiment of the present invention hybridizes tumor biomembranes with liposomes to prepare tumor cell membrane hybridized biomimetic nanoparticles, so that liposomes have good targeting performance.

[0027] The mechanism of action of the bionic nanoparticles provided by the present invention is as follows Figure 1 As shown, when the bionic nanoparticles reach the site of tumor occurrence, when the target recognition agent is PD-1, PD-1 binds to the PD-L1 of the tumor cells, relieving the PD-1 / PD-L1-mediated immunosuppression, allowing T cells to kill tumor cells. At the same time, the bionic nanoparticles enter the cells through the endocytosis of tumor cells, and release the anticancer drugs located between the shells and wrapped by the shells in the tumor cells, promoting tumor cell apoptosis and further enhancing the tumor killing effect.

[0028] The biomimetic nanoparticles provided in the above embodiment enter tumor cells by cell autophagy, which involves the turnover of protein aggregates, cytoplasmic macromolecules and defective organelles. The method is to isolate the contents by forming a double-layer membrane of the autophagosome, and finally deliver the contents to the lysosome, where the "cargo" is degraded. When the autophagy signal appears, the C-terminal amino acid of microtubule-associated protein 3 (Microtubule-Associated Protein 1 Light Chain 3; LC3) is removed and activated to become LC3-I. LC3-I is catalytically connected to a phosphatidylethanolamine molecule, so that it can be inserted into the phagophore membrane and become the fixed LC3-II. LC3-II plays an important role in promoting the membrane fusion of the phagophore and the organelle to be degraded, and in identifying the organelle to be degraded.

[0029] The technical solution of the present invention is further described below through specific examples. In the following specific examples, PD-1-TM-Lipo / ART is a biomimetic nanoparticle with PD-1 as a target inhibitor and artesunate as an anticancer drug, PD-1-TM is a tumor biomembrane-target recognition agent conjugate, and Lipo-ART is a drug-loaded liposome.

[0030] Example 1

[0031] Biomimetic nanoparticle construction Construct humanized PD-1 plasmid and PD-1 overexpression plasmid, amplify the plasmid through competence, select with ampicillin, and extract the plasmid. Determine whether the plasmid sequence is correct. PD-1 overexpression plasmid and psPAX2, pMD2.G were transferred into 293T cells by Lipofectamine 3000 reagent, and fresh medium was replaced after 12 hours and cultured for 48 hours, and the supernatant was collected. Added to H1299 cells, polybrene was added for 12 hours, and fresh medium was replaced, and cultured for 72 hours. After puromycin selection, Western Blot and immunofluorescence were used to verify PD-1 protein expression.

[0032] H1299 PD-1 cells were washed three times with PBS and suspended in IB-1 solution. The mixture was then repeatedly sonicated at 60 W in an ice bath, with 2 s on and 2 s off for 10 min, and then centrifuged at low temperature (800 g, 4 °C, 10 min) to remove intact cells and divided nuclei. The supernatant was centrifuged at 10,000 g, 4 °C for 20 min, and the supernatant was ultracentrifuged at 100,000 g at 4 °C for 60 min to obtain a cell membrane precipitate. The precipitate was taken and suspended in PBS buffer to obtain PD-1-TM.

[0033] Soy lecithin (120 mg), cholesterol (12 mg), and artesunate (20 mg) were weighed and placed in an eggplant-shaped bottle, and dissolved in 30 mL of dichloromethane. Rotate on a rotary evaporator at 35 °C until the solvent is completely evaporated, leaving a uniform film. Add 10 mL of distilled water and hydrate at 60 °C, then use an ultrasonic cell crusher probe to sonicate at 250 w for 10 min. Use a dialysis bag with a molecular weight cutoff of 3500 Da for at least 24 h, and then filter with 0.22 μM to obtain Lipo-ART.

[0034] The mass ratio of Lipo-ART to PD-1-TM was Lipo-ART: PD-1-TM = 1: 0, 1: 0.125, 1: 0.25, 1: 0.5, 1: 1, 1: 2, 1: 4, and 0: 1. Finally, the mass ratio of Lipo-ART to PD-1-TM was 1: 0.5, and PD-1-TM-Lipo / ART was prepared by extrusion.

[0035] Example 2

[0036] Characterization test Morphological detection: The particle size and Zeta potential of PD-1-TM-Lipo / ART were measured by dynamic light scattering. After negative staining with 1% uranyl acetate, the morphology was observed by transmission electron microscopy.

[0037] Membrane fusion detection: Two lipophilic dyes, NBD-PE and rhodamine DHPE, were dissolved in chloroform and then evaporated in a glass vial to form a thin film. NBD-PE-labeled PD-1-TM and rhodamine DHPE-labeled liposomes were prepared and then further prepared into engineered nanoparticles. The energy transfer was detected by fluorescence and the FRET efficiency was calculated.

[0038] Stability test: PD-1-TM-Lipo / ART was incubated with 50 μg / mL trypsin to prepare trypsin-digested biomimetic nanoparticles and evaluate their stability. The trypsin-treated PD-1-TM-Lipo / ART solution was suspended in water at a concentration of 1 mg / mL and stored under anaerobic conditions at 4°C or in air at room temperature. At specific time points over 7 days, the size of the samples was measured by dynamic light scattering to detect aggregation.

[0039] Drug loading capacity and encapsulation efficiency detection: PD-1-TM-Lipo / ART was dissolved in acetonitrile, and the ART concentration was determined by HPLC and the drug loading capacity and encapsulation efficiency of ART were calculated.

[0040] Drug release assay: 1 mL of PD-1-TM-Lipo / ART was added to a dialysis bag (MWCO 8000 Da), immersed in 10 mL of release medium, and incubated at 37 °C with shaking at 120 rpm. At each preset time point, 0.3 mL of aliquots were drawn and immediately added with an equal volume of fresh release solution. The release of ART was determined by chemiluminescent microparticle method.

[0041] Transmission electron microscopy imaging was used to observe the preparation effect of PD-1-TM-Lipo / ART bionic nanoparticles; FRET was used to detect membrane fusion; dynamic light scattering was used to detect the effect of time on the particle size and Zeta potential of PD-1-TM-Lipo / ART to obtain the stability of bionic nanoparticles; high performance liquid chromatography was used to detect the encapsulation efficiency and drug loading of artesunate in PD-1-TM-Lipo / ART nanoparticles.

[0042] Figure 2A in the figure is Western Blot detection of PD-L1 expression in NSCLC cell lines. B is Western Blot detection of PD-1 expression in H1299 cells after overexpression (OE) of PD-1. C is immunofluorescence detection of PD-1 expression in wild-type H1299 and PD-1 overexpressing H1299 cells (H1299 PD-1). D is Western Blot detection of cell membrane extraction of H1299 PD-1. β-tubulin is a cytoplasmic internal reference, and Na + / K + -ATPase is the cell membrane internal reference. E is Western Blot detection of PD-1 expression in H1299 PD-1, H1299 PD-1 cell membrane (PD-1-TM) and PD-1-TM-LIPO / ART. F is transmission electron microscopy imaging of artesunate nanoparticles (NP / ART), PD-1-TM and PD-1-TM-Lipo / ART. GH is dynamic light scattering detection of particle size and Zeta potential of PD-1-TM-Lipo / ART.

[0043] By detecting the expression of PD-L1 in NSCLC cell lines A549, H1975, H1299, H23 and PC-9, Figure 2 As shown in A, H1299 has a high expression of PD-L1, which means that there are many binding sites with PD-1, so H1299 was selected as the object of cell membrane extraction. In addition, PD-1 was overexpressed in H1299 cells ( Figure 2 B and C), and extract cell membranes ( Figure 2 D in the figure). Subsequently, the prepared PD-1 overexpressed H1299 cell membrane (PD-1-TM) was coated on Lipo-ART by ultrasound at a ratio of artesunate nanoparticles (Lipo-ART): PD-1-TM = 1: 0.5, thereby obtaining engineered biomimetic nanoparticles PD-1-TM-Lipo / ART ( Figure 2 E and F in the figure). The particle size of PD-1-TM-Lipo / ART remained around 150 nm and the Zeta potential remained around 80 as the number of days increased. The results suggest that PD-1-TM-Lipo / ART has good stability ( Figure 2 G and H in the figure).

[0044] Figure 3A in the figure shows the different ratios of PD-1-TM and Lipo-ART in confocal imaging. DiD-labeled ART NPs are red; DiO-labeled PD-1-TM is green. B shows the uptake of PD-1-TM-Lipo / ART by NSCLC cells H1299 in confocal imaging. C shows the fluorescence of H1299 cells (NC) without PD-1-TM-Lipo / ART and the fluorescence of H1299 cells with PD-1-TM-Lipo / ART obtained by flow cytometry, *** P <0.001.

[0045] In order to determine the optimal ratio of PD-1-TM and ART NPs, PD-1-TM-Lipo / ART with different mass ratios were prepared. When the overlap of PD-1-TM and ART NPs in the immunofluorescence image was the best, the concentration was considered to be the optimal ratio, such as Figure 3 As shown in A, PD-1-TM-Lipo / ART was prepared by selecting Lipo-ART: PD-1-TM = 1: 0.5. After adding DiD and DiO labeled PD-1-TM-Lipo / ART to NSCLC cells for 4 h, it can be observed that the engineered bionic nanoparticles enter the cells ( Figure 3 B) and the fluorescence intensity of the cells increased significantly ( Figure 3 C), which suggests that PD-1-TM-Lipo / ART is taken up by NSCLC cells H1299.

[0046] Figure 4 A in the figure is an immunofluorescence study of PD-1-TM-Lipo / ART (DiO-labeled green) uptake by NSCLC cells H1299, normal cells HUVEC and B2B cells. B is a CCK-8 experiment to detect the growth inhibitory effect of PD-1-TM-Lipo / ART on H1299, HUVEC and B2B. C is a Western Blot experiment to detect the protein expression of PD-L1 and LC3 in H1299 cells after PD-1-TM-Lipo / ART. D is an immunofluorescence study of the co-localization of LC3-II (red) and PD-L1 (green) in H1299 cells after PD-1-TM-Lipo / ART.

[0047] In order to verify the targeting of PD-1-TM-Lipo / ART to NSCLC cells, NSCLC cells H1299, normal cells human umbilical vein epithelial cells (HUVEC) and human normal lung epithelial cells (B2B) were treated with PD-1-TM-Lipo / ART, respectively. Figure 4As shown in A, PD-1-TM-Lipo / ART is more enriched in H1299 cells after 4 hours of action. Although normal cells also show a small amount of uptake, the killing effect of PD-1-TM-Lipo / ART on H1299 cells is much greater than that on normal cells ( Figure 4 B in the figure). Western Blot results showed that PD-1-TM-Lipo / ART could reduce PD-L1 in H1299 cells and induce the increase of autophagy-related protein LC3-II ( Figure 4 C). When PD-1-TM-Lipo / ART acted on H1299 cells, immunofluorescence co-localization showed that PD-L1 and LC3-II almost overlapped ( Figure 4 D in the figure), which suggests that PD-1-TM-Lipo / ART is likely to induce PD-L1 autophagic degradation. In summary, PD-1-TM-Lipo / ART can fight against tumors and immune escape by inhibiting NSCLC cell proliferation and inducing PD-L1 autophagic degradation.

[0048] In summary, the biomimetic nanoparticle PD-1-TM-Lipo / ART provided in the specific embodiment of the present invention can inhibit NSCLC cell proliferation and induce PD-L1 autophagy degradation to fight against tumors and immune escape. It has great therapeutic potential and a clear mechanism of action, which provides a new strategy for the treatment of lung cancer.

[0049] Although the disclosure is disclosed as above, the protection scope of the disclosure is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the disclosure, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. A bionic nanoparticle, characterized in that: It includes an outer shell and an anticancer drug, wherein the outer shell is obtained by fusion of a phospholipid bilayer and a tumor biomembrane-target recognition agent conjugate, the anticancer drug is distributed between the phospholipid bilayers and in the outer shell cavity, and the target recognition agent is bound to the outer side of the tumor biomembrane.

2. The biomimetic nanoparticle according to claim 1, characterized in that: The anticancer drug is selected from any one or more of artemisinin, dihydroartemisinin, artesunate, artemether, carboplatin, mitomycin, exotecan, cisplatin, vinorelbine, paclitaxel, docetaxel, vinblastine, pemetrexed, bevacizumab, gefitinib, erlotinib, icotinib, osimertinib, recombinant human endostatin, and nivolumab.

3. The biomimetic nanoparticle according to claim 1, characterized in that: The target recognition agent is an antibody against PD-1 or any other cancer cell-specific membrane protein.

4. The biomimetic nanoparticle according to claim 1, characterized in that: The phospholipid bilayer comprises phospholipids and cholesterol, wherein the phospholipids are selected from any one or more of egg yolk lecithin, soybean lecithin, hydrogenated soybean lecithin, distearoyl phosphatidylcholine, dioleoyl lecithin, dimyristoyl phosphatidylcholine, 1-palmitoyl-2-oleoyl lecithin, lauroyl lecithin, dimyristoyl lecithin, dilauroyl phosphatidylglycerol, dipalmitoyl phosphatidic acid, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphatidylserine, dipalmitoyl phosphatidyldiserine, dipalmitoyl phosphatidylcholine, brain phosphatidylserine, brain sphingomyelin, dipalmitoyl sphingomyelin, distearoyl sphingomyelin, and distearoyl phosphatidylethanolamine.

5. The biomimetic nanoparticle according to claim 4, characterized in that: Cholesterol accounts for 6% to 10% of the mass of the phospholipid bilayer.

6. The biomimetic nanoparticle according to claim 1, characterized in that: The mass proportion of the anticancer drug in the bionic nanoparticles is 5% to 15%.

7. A method for preparing the bionic nanoparticles according to any one of claims 1 to 6, characterized in that: The following steps are involved: S1: combining the target recognition agent with the tumor biofilm to obtain the target recognition agent-TM; S2: dissolving phospholipids, cholesterol and anticancer drugs in an organic solvent, removing the organic solvent after mixing, obtaining a film, hydrating the film and mechanically dispersing it to obtain drug-loaded liposomes; S3: Drug-loaded liposomes and target recognition agent-TM were mixed and biomimetic nanoparticles were prepared using extrusion method.

8. An application of the bionic nanoparticles according to any one of claims 1 to 6, characterized in that: The application includes: using the bionic nanoparticles to prepare drugs and / or diagnostic reagents for treating lung cancer.

9. The use according to claim 8, characterized in that The lung cancer is non-small cell lung cancer.

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