Bionic nano composite material as well as preparation method and application thereof

Abstract

The invention discloses a bionic nano composite material as well as a preparation method and application thereof, and belongs to the technical field of medical materials. The bionic nano composite material comprises hollow mesoporous silicon dioxide particles; each hollow mesoporous silica particle comprises a shell layer and an internal cavity; the decitabine and the SGC-CBP30 are loaded in the inner cavity, and the inner cavity is filled with the decitabine; a plurality of mesopores are distributed in the shell layer; the hollow mesoporous silica particles are coated with a CD4 + T cell membrane. In the application of treating psoriasis, the bionic nano composite material shows excellent biocompatibility in a skin lesion microenvironment, has good selectivity to keratinocytes and Th17 cells, and is competitively combined with IL-23 to prevent the interaction between IL-23 and CD4 + T cells, so that the psoriasis treatment effect is improved, and the psoriasis treatment effect is improved. The effect of inhibiting the differentiation of CD4 + T cells to Th17 cells so as to reduce the generation of IL-17 and the proliferation of keratinocytes is achieved.

Description

Technical Field

[0001] The present application relates to a bionic nanocomposite material and a preparation method and application thereof, belonging to the technical field of medical materials. Background Art

[0002] Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes, which form thick scaly plaques on the skin surface. Psoriasis has a high recurrence rate and is difficult to cure completely, which seriously affects the life and mental health of patients. In addition, the systemic inflammation associated with psoriasis leads to a higher risk of death. Psoriasis is also associated with many complications, including joint damage, cardiovascular disease, stroke, hypertension, metabolic syndrome and chronic kidney disease.

[0003] The IL-23 / IL-17 signaling pathway is crucial in the pathogenesis of psoriasis, an inflammatory skin disease characterized by excessive proliferation of keratinocytes and infiltration of immune cells. During the development of psoriasis, dendritic cells and macrophages are recruited into the psoriasis microenvironment and synthesize IL-23 in response to various stimuli such as microbial components and stress signals. IL-23 can promote CD4 + T cells differentiate into Th17 cells, which are characterized by the production of IL-17 proinflammatory cytokines. IL-17 stimulates keratinocytes to produce antimicrobial peptides, chemokines, and other proinflammatory cytokines, including TNF-α and IL-6. This leads to the recruitment and activation of other immune cells, forming a feedback loop that perpetuates inflammation and keratinocyte proliferation. Targeting the IL-23 / IL-17 pathway is very effective in treating psoriasis. In recent years, the U.S. Food and Drug Administration (FDA) has approved a variety of inhibitors targeting the IL-23 / IL-17 signaling axis for the treatment of psoriasis. For example, monoclonal antibodies (such as Secukinumab, Ixekizumab) bind to IL-17A and prevent receptor interaction. These drugs reduce the activation and proliferation of keratinocytes by blocking IL-17, thereby reducing plaque formation and inflammation. Although IL-17 and IL-23 inhibitors have greatly advanced the treatment of psoriasis, there are still challenges in terms of safety, long-term effects, cost, accessibility, and patient compliance.

[0004] Epigenetic regulation plays a crucial role in the pathogenesis of psoriasis, affecting gene expression without changing the basic DNA sequence. Epigenetic regulation is crucial for regulating the IL-23 / IL-17 signaling pathway, and epigenetic inhibitors have emerged as a promising therapeutic approach for the treatment of psoriasis. The main types of epigenetic inhibitors include DNA methyltransferase inhibitors and histone acetyltransferase inhibitors. For example, decitabine is a DNA hypomethylating agent that can be used to treat specific types of cancer, especially acute myeloid leukemia and myelodysplastic syndrome. Decitabine inhibits DNA methyltransferases, resulting in DNA hypomethylation and affecting gene expression, which can induce cell cycle arrest and apoptosis in cancer cells. In inflammatory diseases such as arthritis, decitabine can selectively induce apoptosis of Th1 and Th17 cells. SGC-CBP30 is a small molecule compound that is a potent and selective histone acetyltransferase inhibitor. SGC-CBP30 inhibits the production of Th17 cytokines by Th17 cells and controls CD4 + Although these epigenetic drugs hold great promise for the treatment of psoriasis, they are still under investigation and not widely used. Therefore, significant challenges related to the specificity, safety, administration, and resistance of these molecular inhibitors must be addressed to characterize their therapeutic potential. Summary of the invention

[0005] In order to improve the therapeutic effect of the IL-23 / IL-17 pathway of psoriasis and improve the treatment of psoriasis, the present application provides a bionic nanocomposite material and a preparation method and application thereof. The provided bionic nanocomposite material is a simulated CD4 + Biomimetic nanoparticles of T cells loaded with dual epigenetic drugs, which effectively loaded decitabine (DAC) and SGC-CBP30 (CBP) molecules by binding to CD4 + T cell membrane, in the application of drug for the treatment of psoriasis, shows excellent biocompatibility and selectivity for keratinocytes and Th17 cells in the microenvironment of skin lesions, and competitively binds to IL-23, preventing IL-23 from binding to CD4 + T cell interactions, which inhibit CD4 + Differentiation of T cells into Th17 cells reduces IL-17 production and keratinocyte proliferation.

[0006] This application adopts the following technical solutions:

[0007] A bionic nanocomposite material, comprising hollow mesoporous silica particles;

[0008] The hollow mesoporous silica particles include a shell layer and an internal cavity;

[0009] A plurality of mesopores are distributed on the shell layer;

[0010] The internal cavity and mesopores are loaded with decitabine and SGC-CBP30;

[0011] The hollow mesoporous silica particles are coated with CD4 + T cell membrane.

[0012] The CD4 + The T cell membrane is connected to the shell surface of the hollow mesoporous silica particles through amino functional groups.

[0013] Optionally, the loading amount of decitabine in the hollow mesoporous silica particles is 0.45% to 2.2%.

[0014] Optionally, the loading amount of SGC-CBP30 in the hollow mesoporous silica particles is 0.51% to 2.5%.

[0015] Optionally, the weight ratio of decitabine to SGC-CBP30 is 1:0.2-5.

[0016] Alternatively, hollow mesoporous silica particles loaded with decitabine and SGC-CBP30 are stained with CD4 + The volume ratio of T cell membrane is 1:0.5~1.5.

[0017] Optionally, the specific surface area of ​​the hollow mesoporous silica particles is 59.6622 m 2 / g.

[0018] Optionally, the pore volume of the hollow mesoporous silica particles is 0.288417 cm 3 / g.

[0019] Optionally, the particle size of the hollow mesoporous silica particles is 92 to 104 nm.

[0020] Optionally, the CD4 + The thickness of T cell membrane is 4 to 6 nm.

[0021] Optionally, the Zeta potential of the bionic nanocomposite material is 11.7-17.1 mV.

[0022] DAC is a DNA hypomethylating drug that inhibits the proliferation of keratinocytes in a psoriasis-like inflammatory environment. In inflammatory diseases, DAC selectively induces apoptosis of Th1 and Th17 cells. The histone acetyltransferase inhibitor CBP inhibits the production of Th17 cytokines by Th17 cells and controls the expression of CD4+ T cells.

[0023] According to another aspect of the present application, a method for preparing the above-mentioned bionic nanocomposite material is provided, comprising the following steps:

[0024] S1, respectively obtain hollow mesoporous silica particles, CD4 + T cell membrane;

[0025] S2, mixing the dimethyl sulfoxide aqueous solution containing decitabine and SGC-CBP30 with the suspension containing hollow mesoporous silica particles, and stirring to obtain hollow mesoporous silica particles loaded with decitabine and SGC-CBP30;

[0026] S3, hollow mesoporous silica particles containing decitabine and SGC-CBP30 were mixed with CD4 + The mixed solution of T cell membrane is extruded to obtain the bionic nanocomposite material.

[0027] Optionally, in step S3, the mixed solution is prepared by adding HMDC nanoparticles to a PBS solution to prepare an HMDC nanoparticle solution, and then mixing the HMDC nanoparticle solution with the CD4 obtained in step S1. + The T cell membrane solutions are mixed to obtain the mixed solution.

[0028] Optionally, the concentration of the HMDC nanoparticle solution is 1 to 5 mg / mL.

[0029] Those skilled in the art can select the HMDC nanoparticle solution and the CD4 obtained in step S1 according to actual needs. + Volume ratio of T cell membrane solution.

[0030] Optionally, the HMDC nanoparticle solution is mixed with the CD4 + The volume ratio of the T cell membrane solution is 1:1.

[0031] Optionally, in step S2, the weight ratio of decitabine, SGC-CBP30, and hollow mesoporous silica particles is (0.01-1):(0.01-1):1.

[0032] Optionally, in step S2, the stirring conditions include: stirring time is 18 to 24 hours;

[0033] Optionally, in step S3, the extrusion conditions include: extrusion 25 to 35 times.

[0034] Optionally, in step S1, the preparation method of the hollow mesoporous silica particles is: using solid silica balls as a template, synthesizing hollow mesoporous microspheres by hard template etching method, mixing the hollow mesoporous microspheres with 3-aminopropyltriethoxysilane solution, stirring, so that amino functional groups are formed on the surface of the hollow mesoporous microspheres, and obtaining the hollow mesoporous silica particles;

[0035] Optionally, in step S1, the CD4 + The method for preparing T cell membrane is as follows: TM Mouse CD4 + T cell isolation kit (STEMCELL TM ) Isolation of CD4 from mouse spleen + T cells

[0036] Optionally, the CD4 + The method for preparing T cell membrane includes:

[0037] The spleen was disrupted with PBS containing 2% FBS; the cell suspension was passed through a 40 μm mesh nylon filter to remove aggregates and debris; the cells were centrifuged at 300 g for 10 min and counted at 1 × 10 8 The cells were resuspended in 500 μL of PBS containing 2% FBS and 1 mM EDTA at a concentration of cells / mL; the samples were treated with FcR blockers and transferred to 5 mL polystyrene round-bottom tubes; a protease inhibitor cocktail was added and the mixture was incubated at room temperature for 10 min; magnetic beads were then incubated with the samples and separated using a magnet; flow cytometry was performed using CD45 (FITC-anti-mouse CD45, BioLegend) and CD4 (PE-anti-mouse CD4, BioLegend) antibodies to help identify the isolated cells; the isolated CD4 + T cells were squeezed 20 times by an Avanti micro extruder (Avanti Polar Lipids, USA), and then the cell membranes were subjected to gradient centrifugation; the cells were resuspended in a lysis buffer (20 mM Tris-HCl, pH 7.4; 10 mm KCl; 10 mM MgCl2) and then centrifuged at 3200 g for 5 min. After the centrifugation was completed, the supernatant was aspirated and centrifuged at 20,000 g for 30 min at 4 ° C. The supernatant was the extracted cell membrane to obtain the CD4 + T cell membrane.

[0038] According to another aspect of the present application, there is also provided a use of the above-mentioned bionic nanocomposite material in the preparation of a drug for treating psoriasis.

[0039] The beneficial effects of this application include:

[0040] The bionic nanocomposite material provided in the present application is based on hollow mesoporous silica as a framework, loaded with two epigenetic drugs, decitabine and SGC-CBP30, and the bionic nanocomposite material binds CD4 + T cell membrane, showing excellent biocompatibility and skin absorption capacity, and is selective for keratinocytes and Th17 cells in the microenvironment of psoriasis lesions. In addition, the bionic nanocomposite material of the present application can also competitively bind to IL-23, preventing it from binding to CD4 + T cell interactions, inhibiting CD4 + T cells differentiate into Th17 cells, and inhibit the production of inflammatory cytokine IL-17 and the proliferation of keratinocytes. The cell membrane function of the bionic nanocomposite material of the present application synergizes with DNA demethylation and histone deacetylation activity to inhibit the growth of Th17 and the proliferation of keratinocytes. In the application of the bionic nanocomposite material in the treatment of psoriasis, the dual epigenetic therapy is improved by synergistically inhibiting the IL-23 / IL-17 pathway in psoriasis. Its therapeutic effect has been verified in the IMQ-induced psoriasis mouse model, and it can significantly inhibit PASI score, epidermal thickness, hyperplasia and splenomegaly. The present application provides bionic nanocomposite materials and epigenetic therapies using the materials, which can be used to enhance the treatment of psoriasis and have great clinical potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 The preparation process and characterization of HMDC4M in Example 1 of the present application: (A) Schematic diagram of HMDC4M synthesis; (B) SEM image of HMDC; (C) X-ray diffraction (XRD) analysis of HMDC; (D) Giemsa staining method to identify mouse CD4 + T cell morphology; (E) Identification of CD4 + T cell extracts; (F) Solution photos of HMDC and HMDC4M. (G) TEM images of HMDC4M; (H) Hydration particle size of HMDC and HMDC4M. (I) Zeta potential of HMDC and HMDC4M; (J) CD4 + T cells (CD4T), CD4 + SDS-PAGE images of total proteins in T cell membrane (CD4Tm), HMDC4M or HMDC; (K) Flow cytometry histogram showing the expression of cell membrane protein CD4 (CD45 gated) on HMDC4M; (L) Quantitative analysis of CD4 obtained from (J); (M) Elemental map of HMDC4M.

[0042] Figure 2For the present application, HMDC4M can selectively target Th17 cells in psoriasis for testing: (A) Schematic diagram of the preparation of fluorescently labeled HMDC4M; (B) Confocal images showing the uptake of HMDC4M by Th17 cells, keratinocytes and normal cells, with a scale bar of 50 μm; (C) Silicon content in Th17 cells, keratinocytes and normal cells treated with HMDC4M or HMDC was measured by ICP; (D) Schematic diagram of the establishment of an animal model of psoriasis for in vivo distribution studies; (E) In vivo imaging analysis of IMQ mice injected with HMDC4M at specific time points. (F) Skin penetration was detected along the Z axis using confocal laser scanning microscopy (CLSM); (G) Ex vivo imaging of important organs collected 24 hours after psoriatic mice were treated with HMDC4M; (H) Measurement of silicon content in major organs of HMDC4M-treated psoriatic mice (n=6); (I) Flow cytometry graphs showing the fluorescence signal of Cy7-labeled HMDC4M in single cells isolated from the skin of psoriatic mice; (J) Quantitative data analysis of (I) (n=6), statistical significance was determined by one-way ANOVA and Tukey's test, where *P<0.05, **P<0.01, ***P<0.001; (K) Detection of apoptosis of Th17 cells and keratinocytes induced by HMDC4M.

[0043] Figure 3 For this application CD4 + T cell membrane-encapsulated nanoparticles can neutralize IL-23 in psoriasis: (A) IL-23 clearance assay in psoriasis. Serum from psoriasis mice was collected and incubated with different concentrations of HM4M, HMS or HM4M+anti-IL-23 antibody at 37°C for 2 hours. The supernatant was obtained after centrifugation. The levels of IL-23 (B) and IL-17 (C) in serum were detected by ELISA. (D) The viability of keratinocytes after 48 hours of culture with different supernatants from part (A) was analyzed by one-way ANOVA using Tukey's test. **P<0.01.

[0044] Figure 4For the present application, HMDC4M has an inhibitory effect on IMQ-induced psoriasis dermatitis: (A) Establishment of IMQ-induced psoriasis mouse model; (B) Representative images of skin surface morphology of each group on day 8; (C) Quantification of Psoriasis Area and Severity Index (PASI) score; (D) Representative images of hematoxylin and eosin (HE) staining and proliferating cell nuclear antigen (PCNA) immunostaining of skin sections of different groups on day 8, scale bar is 100 μm; (E) Quantification of epidermal thickness based on histological staining; (F) Quantification of PCNA expression in skin tissue of each group; (G) Representative spleen images (scale bar = 0.5 cm) and HE-stained tissue sections (scale bar = 50 μm) of the designated groups; (H) Spleen weight measurement of the designated groups; Statistical analysis was performed using one-way analysis of variance and Tukey's test, where *P<0.05 and **P<0.01 indicate statistical significance.

[0045] Figure 5 The immunological mechanism of HMDC4M in the treatment of psoriasis in this application: (A) Representative images of 5mC and H3K56Ac immunostaining of skin sections in each group on day 8; scale bar = 100 μm. (B) Flow cytometry detection of Th17 cells in mouse skin; (C and D) Quantitative determination of protein expression of 5mC and H3K56Ac in skin tissues of each group; (E) Flow cytometry quantitative detection of the percentage of Th17 cells in (B); (F) Levels of IL-17 and IL-23 in the serum of psoriasis mice in each group on day 8; One-way ANOVA was performed using Tukey's test, *P<0.05, **P<0.01 (n=6).

[0046] Figure 6 (A)N for this application HMS 2 Adsorption–desorption isotherms and corresponding (B) pore size distribution.

[0047] Figure 7 The loading efficiency and loading capacity of DAC and CBP in HMDC of this application.

[0048] Figure 8 (A) XPS spectrum, (B) high-resolution C1 spectrum, (C) high-resolution N1s spectrum, (D) high-resolution O1s spectrum and (E) high-resolution Si2p spectrum of HMDC in this application.

[0049] Fig. 9 For the present application, the cell survival rate of normal primary mouse skin cells after being treated with different concentrations of HMDC4M for 48 hours.

[0050] Fig.10 The body weights of psoriasis mice in each group of the present application are shown as mean±SD (n=6).

[0051] Fig.11 The body weights of healthy mice treated with PBS or 100 μg / mL HMDC4M for 30 days are shown in the present application. The data are expressed as mean±SD (n=3).

[0052] Fig.12 Representative images of H&E staining of major organs of healthy mice treated with PBS or 100 μg / mL HMDC4M for 30 days for the present application, data are presented as mean ± SD (n = 3). Scale bar: 50 μm.

[0053] Fig.13 In vitro hemolysis test of HMDC4M for this application: (A) HMDC4M at different concentrations was incubated with 5% erythrocytes at 37°C for 48 hours, (B) the suspension was measured at 540 nm using a BioTek Epoch microplate reader. DETAILED DESCRIPTION

[0054] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0055] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0056] Unless otherwise specified, the test methods all adopt conventional methods, and the instrument settings all adopt the settings recommended by the manufacturer, including:

[0057] Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE): Separation (8%) and stacking (4%) gels were prepared by mixing Tris-HCl, bisacrylamide, SDS, TEMED and ammonium persulfate, and the total protein content of the sample was 20 μg. Gel electrophoresis was performed using a Bio-Rad Mini-Protean Tetra electrophoresis system, and the gel after electrophoresis was stained with Coomassie Brilliant Blue staining solution for 10 h, then destained with Coomassie Brilliant Blue destaining solution, and finally the image was captured using a gel imaging system.

[0058] Loading capacity and encapsulation efficiency: The loading capacity (LC) and encapsulation efficiency (EE) of DAC and CBP in HMDC4M were evaluated using high-performance liquid chromatography (HPLC) and a C18 column according to established procedures: LC (wt.%) = loaded drug mass / total nanomaterial mass × 100%; EE (wt.%) = loaded drug mass / total drug mass × 100%.

[0059] Nanomaterial characterization: The sample morphology was examined using a JEOL JSM-6700F scanning electron microscope (SEM) and a Philips-FEI Tecnai G2S-Twin transmission electron microscope (TEM) equipped with a 200 kV field emission gun. X-ray photoelectron spectroscopy (XPS) measurements were performed using an ESCALAB 250 spectrometer. Powder X-ray diffraction (PXRD) patterns were obtained using a Rigaku D-Max 2550 diffractometer with Cu Kα radiation in the range of 2° to 10°. The nitrogen adsorption-desorption isotherms at 77 K were measured using a Micromeritics 2020 analyzer. The 400-4000 cm -1 Fourier transform infrared spectroscopy (FT-IR) of the region.

[0060] Cell culture: HaCaT cells (human immortalized keratinocytes) were cultured in a 5% carbon dioxide environment at 37°C in DMEM supplemented with 10% fetal bovine serum (FBS). The culture medium was changed every 2-3 days. When the cell density reached 70-80%, they were passaged. The culture medium was then removed. The cells were rinsed one or two times with PBS before being digested with 0.25% trypsin for 2-3 minutes. Then, the trypsin was removed in time and DMEM containing 10% FBS was added to stop the digestion. Subsequently, the cells were passaged at a ratio of 1:3. Primary Th17 cells used DMEM containing 20% ​​FBS. To obtain Th17 cells, according to previous reports (Y. Song, L. Zhang, Y. Wang, M. Han, Z. Wang, N. Wang, B. Shao, R. Li, K. Cao, M. Song, Y. Du, F. Yan, Adv Mater 2023, 35, e2210895), CD4 + T was co-cultured with IL-1β (20 ng / ml), IL-6 (20 ng / ml) and IL-23 (20 ng / ml) for 72 hours. Normal single cells were isolated from mouse skin tissue according to previous reports (X. Dai, X. Li, Y. Du, M. Han, Z. Wang, Y. Wang, F. Yan, Y. Liu, Chem Eng J 2023, 459, 141426.). Skin tissue was initially homogenized in modified DMEM medium supplemented with 5% FBS using a syringe plunger. Then, the tissue was digested with Hank's balanced salt solution containing DNase I and Liberase at 37°C for 30 minutes. Cells were cultured in DMEM medium supplemented with 10% FBS for 3 days.

[0061] Cellular uptake of nanoparticles: The silicon content in cells was measured using a Perkin-Elmer NEXION 300× ICP mass spectrometer to quantitatively analyze the cell uptake of nanoparticles at different concentrations. For fluorescence detection, cells were plated at 5×10 5 The cells were seeded at a density of 100 μg / mL in a 12-well plate and cultured overnight. The next day, the old culture medium was replaced with fresh culture medium containing Cy3-labeled nanoparticles and cultured for 30 minutes. After rinsing with PBS, the cells were fixed with 4% paraformaldehyde for 15 minutes. The cell nuclei were stained with DAPI and observed using a Nikon confocal laser scanning microscope.

[0062] In vitro cytotoxicity assay: Cytotoxicity was assessed using the Cell Counting Kit-8 (CCK-8; Dojindo Molecular Technologies). Normal cells were seeded into 96-well plates, and then different concentrations of nanoparticles were added and cultured for 48 h. After 48 h of culture, CCK-8 reagent was added, and the absorbance at 450 nm was measured using a BioTek Epoch microplate reader. Cell apoptosis was assessed using Annexin V and PE staining, followed by flow cytometry analysis.

[0063] Establishment of mouse psoriasis model: Male BALB / c mice (6-8 weeks old) were obtained from Charles River and kept in a pathogen-free environment at room temperature. The Ethics Committee of Jilin University approved the study protocol, and all animal handling procedures complied with the guidelines of the Animal Care and Use Committee of Jilin University. Imiquimod (IMQ) cream (5%) was topically applied to the shaved back skin of mice to establish an IMQ-induced psoriasis-like mouse model. Approximately 62.5 mg of IMQ cream was applied to each mouse daily. Mice were monitored daily for symptoms of psoriasis, typical symptoms of which include erythema, desquamation, and skin thickening. The severity of psoriasis-like lesions was assessed using the Psoriasis Area and Severity Index (PASI) scoring system, which assesses erythema, scaling, and skin thickness. Mice were randomly divided into five groups for animal treatment: PBS group, HMS group, HM4M group, DAC+CBP group, and HMDC4M group. From day 4 to day 8, mice were treated with topical medication every day. The dose of nanoparticles was 50 μg / mL, and the doses of DAC and CBP were 1 μM and 0.5 μM, respectively, which were equivalent to the loading doses in HMDC4M.

[0064] PASI scoring criteria: (1) Erythema: 0 points for no erythema, 1 point for light red erythema, 2 points for red erythema, 3 points for dark red erythema, and 4 points for very dark erythema. (2) Scaling: 0 points for no scaling, 1 point for some lesions covered with scales, 2 points for most lesions covered with scales, 3 points for almost all lesions covered with stratified scales, and 4 points for all lesions covered with thick scales. (3) Thickness: 0 points if the lesions are level with normal skin; 1 point if the lesions are slightly raised; 2 points if the lesions are moderately raised; 3 points if the lesions are thick and obviously raised; and 4 points if the lesions are highly thickened and obviously raised. The average total score of each group was plotted as a curve.

[0065] Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining: The skin and major tissue organs of the mice were fixed in 10% neutral buffered formalin, embedded in paraffin, and cut into 5-10 μm thick sections. IHC and H&E staining were performed according to the established protocol described in the applicant's previous article (Y.Du, M.Han, K.Cao, Q.Li, J.Pang, L.Dou, S.Liu, Z.Shi, F.Yan, S.Feng, ACS Nano 2021, 15, 17689–17704.). For IHC staining, the skin sections were heated at 60°C for 30 minutes, deparaffinized in Histo-Clear for 10 minutes, dehydrated with a series of ethanol solutions (100%, 95%, and 70%), and then rinsed with PBS. All sections were microwaved at 70% power for 10 minutes in 10mM citric acid buffer (pH 6.0) to remove antigens. Endogenous peroxidase activity was blocked with 3% hydrogen peroxide for 20 minutes and then rinsed with PBS. Sections were blocked with 10% horse serum for 40 minutes to prevent nonspecific binding and then blocked with avidin and biotin for 15 minutes each. Sections were incubated overnight at 4°C with primary antibodies such as PCNA (Cell Signaling Technology, #12727), 5mC (Invitrogen, MA5-31475), and H3K56Ac (Invitrogen, MA5-32138). Samples were developed with 3,3′-diaminobenzidine (DAB), counterstained with hematoxylin, and then mounted. Stained slides were photographed and analyzed using a Nikon microscope equipped with a high-resolution condenser camera and ImageJ software.

[0066] ELISA: Serum samples were collected from psoriatic mice and the levels of IL-17 or IL-23 were quantified using a mouse ELISA kit from Invitrogen according to the manufacturer’s protocol. Absorbance readings were taken using a BioTek microplate reader.

[0067] In vivo biodistribution: Psoriasis mice were injected with different Cy7-labeled nanoparticles (50 μg / mL, 100 μl) and randomly divided into three groups (n=3). Mice were euthanized within 0 to 24 hours after administration, and their skin and vital organs (heart, liver, spleen, lung and kidney) were collected and imaged using an in vivo imaging system (IVISlumina3 system, Perkin-Elmer). Single cells in the skin were separated and filtered using a 40-micron nylon mesh filter (Corning). CD4 + T cells (CD4+IL-17+; PE-anti-mouse CD4, BioLegend; APC-IL-17A monoclonal antibody, eBioscience TM ). For quantitative analysis, the tissues were weighed and digested in aqua regia by heating (80°C) for three days. The silicon content in the samples was measured using ICP-AES (Perkin-Elmer Optima 3300DVICP spectrometer). In the skin penetration test, dorsal skin samples were collected and stored on glass slides. The depth of Cy7 in the skin was then observed along the Z axis using a confocal laser scanning microscope (CLSM).

[0068] In vivo biocompatibility study of HMDC4M: Male BALB / c mice (4-6 weeks old, n=3) were shaved on the back and treated with HMDC4M (100 μg / mL) or PBS. After 30 days, the mice were euthanized, and their major organs (heart, liver, spleen, lung and kidney) were harvested and H&E staining was performed to examine the histopathological changes (refer to K.Cao, Y.Du, X.Bao, M.Han, R.Su, J.Pang, S.Liu, Z.Shi, F.Yan, S.Feng, Small 2022, 18, 2106558.). In the red blood cell (RBCs) hemolysis test, Ficoll-Paque TM PLUS RBCs were obtained from mice. Different concentrations of HMDC4M were incubated with 5% RBCs in PBS at room temperature for 48 hours. After incubation, the suspension was centrifuged at 6000g for 20 minutes. The absorbance was measured at 540nm using a BioTek Epoch microplate reader. A 5% RBCs lysate was used as a positive control.

[0069] Statistical analysis: Unless otherwise stated in the figure legends or the main text, in vitro experiments were performed at least three times. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey post-test. All analyses were performed using GraphPad Prism 9 software. The significance threshold was set at P < 0.05, and all reported P values ​​are two-tailed.

[0070] Example 1 Preparation of biomimetic nanocomposite material (HMDC4M)

[0071] The preparation steps of biomimetic nanocomposites are as follows: Figure 1 As shown in A, the specific steps are:

[0072] Step 1, preparation of HMS particles: Synthesis of hollow mesoporous silica (HMS), hollow mesoporous silica (HMS) was synthesized by hard template etching method as a skeleton, having a hollow mesoporous structure, and can be used as a drug carrier. The specific steps are as follows: ethanol (74 mL) and ammonia solution (3.2 mL) were dissolved in deionized water (10 mL), stirred at 50 ° C for 30 min, then, 6 mL of tetraethoxysilane (TEOS) solution was added and the mixture was stirred at room temperature for another 6 h, dialyzed with a MWCO 12-14 kDa membrane and freeze-dried to obtain solid silica spheres (sSiO 2 ); 75 mg of hexadecyltrimethylammonium bromide (CTAB) was added to 37.5 mL of ethanol / water mixture with a volume ratio of 1:2 (v / v) and stirred for 30 min, and then 40 mg of sSiO 2 The template was stirred for 30 min, and then an aqueous ammonia solution (28%, 300 μL) and a TEOS solution (125 μL) were added and stirred at room temperature for 12 h to allow CTAB to form a sSiO 2 The resulting solution was dialyzed with deionized water (MWCO 12-14 kDa) and replaced 5 or 6 times a day for 3 consecutive days, and then centrifuged to obtain a product containing a mesoporous shell; the product containing a mesoporous shell (25 mg) was mixed with Na 2 CO 3 (116 mg) was added into water (5 mL) and mixed, and stirred at 50 ° C for 12 h to remove the template. After freeze-drying (EyeLA FDU-1200, -38.3 ° C, 29.5 Pa), it was added into 20 mg / mL ammonium nitrate ethanol solution and immersed at 45 ° C for 6 h. The product was washed three times with ethanol and collected by centrifugation to obtain HMS without functional groups. The HMS without functional groups (25 mg) was dispersed in ethanol (12.5 mL) and stirred for 15 min. Then 25 μL of 50% concentration of 3-aminopropyltriethoxysilane (APTES) aqueous solution was added and stirred at 45 ° C for 24 h to functionalize it with the amino groups on the surface of HMS. After that, HMS nanoparticles were obtained by dialysis and freeze-drying.

[0073] Step 2. Get CD4 + T cell membrane: using EasySep TM Mouse CD4 + T cell isolation kit (STEMCELL TM) Isolation of CD4 from mouse spleen + T cells. Briefly, spleens were disrupted with PBS containing 2% FBS. The cell suspension was passed through a 40 μm mesh nylon filter to remove aggregates and debris. Cells were centrifuged at 300 g for 10 min and counted at 1 × 10 8 The cells were resuspended in 500 μL of PBS containing 2% FBS and 1 mM EDTA at a concentration of cells / mL. The samples were treated with FcR blocker and transferred to 5 mL polystyrene round-bottom tubes. A protease inhibitor cocktail was added and the mixture was incubated at room temperature for 10 min. Subsequently, magnetic beads were incubated with the samples and separated using a magnet. Flow cytometry used CD45 (FITC-anti-mouse CD45, BioLegend) and CD4 (PE-anti-mouse CD4, BioLegend) antibodies to help identify the isolated cells. The CD4 isolated above was lysed with cell membrane lysis buffer. + T cells and squeezed 20 times through an Avanti microextruder (Avanti Polar Lipids, USA). Then, the cell membranes were subjected to gradient centrifugation. The cells were first resuspended in lysis buffer (20mM Tris-HCl, pH 7.4; 10mm KCl; 10mM MgCl2) and then centrifuged at 3200g for 5min. After centrifugation, the supernatant was aspirated and centrifuged at 20000g for 30min at 4°C. The supernatant was the extracted cell membrane to obtain CD4 + Solution of T cell membranes.

[0074] Step 3, preparation of HMDC: prepare a drug combination solution according to the concentrations of decitabine (DAC) and SGC-CBP30 (CBP) of 10 μM and 5 μM, namely, add decitabine (DAC) (HY-A0004, MedChemExpress) and SGC-CBP30 (CBP) (SML1133, Sigma-Aldrich) to 1% dimethyl sulfoxide aqueous solution to prepare a drug combination solution; add HMS nanoparticles to water to prepare a 500 μg / mL HMS suspension; mix 1 mL of the drug combination solution with 9 mL of the HMS suspension, and then stir magnetically for 24 hours to allow DAC and CBP to self-assemble in the HMS and then be co-loaded in the HMS particles to obtain HMS nanoparticles loaded with DAC and CBP molecules, which are labeled as HMDC.

[0075] Among them, in 50 μg / mL HMS solution, the loading concentrations of DAC and CBP were 1 μM and 0.5 μM, 0.228 μg / mL and 0.254 μg / mL, respectively, with a mass ratio of approximately 1:1, expressed as the same mass.

[0076] Step 4, preparation of HMDC4M: HMDC nanoparticles were added to PBS solution to prepare a 2.5 mg / mL HMDC nanoparticle solution, and then the HMDC nanoparticle solution was mixed with the CD4 obtained in step S2. + The T cell membrane solution was mixed at a volume ratio of 1:1 to obtain a mixture, and the mixture was extruded 25-35 times using an Avanti micro extruder (Avanti Polar Lipids) to allow the HMDC nanoparticles to be attached to the CD4 + The T cell membranes were packaged together and squeezed, and then the samples were washed with PBS and centrifuged at 5000 g for two rounds, each for 10 min, to obtain a biomimetic nanocomposite material, which was labeled as HMDC4M.

[0077] N of HMS prepared in step S1 2 Adsorption / desorption isotherms such as Figure 6 As shown in Figure 2, the BET specific surface area and pore volume of HMS are 59.6622 m 2 g -1 and 0.288417cm 3 g -1 .

[0078] The method of steps S1 to S4 is adopted, except that in step S3 Figure 7 DAC and CBP were co-loaded into HMS with different raw material dosage ratios as shown to test the drug loading performance of the material. The drug ratio and the corresponding drug loading amount and drug loading rate are shown in Figure 7 As shown, when the drug ratio is 0.5:0.5:1 (m / m), the maximum drug loading can reach 87.5%.

[0079] The loading concentrations of DAC and CBP were set at 1 μM and 0.5 μM (50 μg / mL of HMDC), respectively, within their respective clinically relevant dose ranges for potential clinical translation. These concentrations were optimized to maximize the loading capacity of the delivery system for effective containment in the hollow mesoporous structure of HMS. Scanning electron microscopy (SEM) of HMDC obtained in preparation step S3 showed that the morphology of HMDC was a spherical structure with a uniform particle size close to 100 nm ( Figure 1 B)

[0080] The small-angle X-ray diffraction pattern of HMDC shows a distinct diffraction peak in the range of 2-3° at 2θ, indicating the presence of mesoscopic order in the shell structure ( Figure 1 C).

[0081] Isolation of CD4 from mouse spleen + T cells, used to prepare CD4 + T cell membrane biomimetic nanocomposite. CD4+ The morphology of T cells is small and round, with dense nuclei and thin cytoplasm edges ( Figure 1 D), CD45 and CD4 are both positive ( Figure 1 E).

[0082] After coating with the cell membrane, the HMDC4M solution showed no obvious aggregation or precipitation, showing good dispersibility and stability ( Figure 1 F). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the hollow mesoporous structure of HMDC4M, with a particle size of 102±4.6nm and a cell membrane thickness of approximately 5nm ( Figure 1 G and Figure 1 H). Compared with HMDC (13.8 ± 1.2 mV), the potential of HMDC4M was reversed to -14.4 ± 2.7 mV. This is attributed to CD4 + Negative potential of T cell membrane ( Figure 1 I) Confirmation of CD4 by evaluating total protein profile by SDS-PAGE + Packaging of T cell membranes, protein profile of HMDC4M and CD4 + T cell membranes were comparable, indicating that the HMDC4M protein was fully retained ( Figure 1 J). Flow cytometry is helpful to detect the expression of surface protein CD4. Flow cytometry showed that HMDC4M expressed high levels of membrane proteins CD45 and CD4, indicating successful encapsulation of CD + T cell membrane Figure 1 K and Figure 1 L). Scanning electron microscope-energy dispersive X-ray (STEM-EDX) elemental mapping showed that there were a large number of P elements (representing cell membrane components) around HMDC4M, proving that the cell membrane was successfully coated ( Figure 1 M).

[0083] Comparative Example 1: Cell membrane-coated HMS (HM4M) without drug loading

[0084] Preparation of HMS particles and acquisition of CD4 + The steps of preparing T cell membrane are the same as S1 and S2 in Example 1. The preparation steps of HM4M are to mix HMS nanoparticles with CD4 + The mixture was mixed with the T cell membranes at a volume ratio of 1:1, and the mixture was extruded 25-35 times using an Avanti micro extruder (Avanti Polar Lipids) to allow the HMS nanoparticles to bind to the CD4 + The T cell membranes were packaged together, squeezed, and the samples were resuspended in PBS and centrifuged twice at 5000 g for 10 min each to obtain cell membrane-coated HMS, which was labeled as HM4M.

[0085] Test Example 1 is selective for keratinocytes and Th17 cells

[0086] First, fluorescent dye Cy3 or Cy7 is attached to the HMDC nanoparticles prepared in Example 1 to facilitate tracking them in vitro or in vivo ( Figure 2 A). Figure 2 B shows that Th17 cells treated with HMDC4M prepared in Example 1 showed obvious red fluorescence, while normal cells did not show obvious fluorescence intensity. Nanoparticles without cell membrane coating did not show obvious fluorescence signals in Th17 cells and normal cells. These results show that HMDC4M can specifically target Th17 cells. Strong fluorescence signals were also observed in keratinocytes treated with HMDC4M, indicating that HMDC4M has the ability to target keratinocytes. ICP quantitative experiments confirmed the cellular uptake ability of HMDC4M ( Figure 2 C). The targeting specificity of HMDC4M on Th17 cells in the psoriasis lesion microenvironment was verified by establishing a psoriasis mouse model ( Figure 2 D), Cy7-labeled HMDC4M was applied to the skin lesions and the changes in fluorescence intensity were monitored. Over time, the fluorescence intensity of HMDC4M gradually decreased, indicating that it was effectively absorbed and penetrated by the skin tissue ( Figure 2 E). Confocal laser scanning microscopy (CSLM) showed excellent skin permeability of approximately 80 μm ( Figure 2 F). In addition, the main organs of the mice were collected 24 hours later for fluorescence and ICP analysis, and the results showed that HMDC4M mainly accumulated in the liver and promoted the excretion of nanomaterials through liver metabolism ( Figure 2 G and Figure 2 H). Flow cytometry analysis of Th17 cells (CD4 + IL17 + ), and found that there was a strong Cy7 fluorescence signal in Th17 cells ( Figure 2 I and Figure 2 J). These in vivo data confirm the targeting specificity of HMDC4M for Th17 cells in the microenvironment of psoriasis lesions. The interaction between keratinocyte proliferation and Th17 cell dysregulation is a driving force for the onset and progression of psoriasis. Finally, HMDC4M can induce apoptosis of Th17 cells and keratinocytes in a dose-dependent manner ( Figure 2 K). Importantly, HMDC4M showed minimal cytotoxicity to normal cells at various concentrations, highlighting its selectivity and biocompatibility ( Fig. 9 ).

[0087] Test Example 2CD4 +T cell membrane-camouflaged nanoparticles prevent IL-23-induced IL-17 production

[0088] In psoriasis, activated dendritic cells overproduce the proinflammatory cytokine IL-23 by interacting with naive CD4 + Binding to receptors on T cells leads to CD4 + T cells differentiate into Th17 cells and keratinocyte proliferation. Once differentiated, Th17 cells proliferate and migrate to the skin, leading to the inflammatory response that is characteristic of psoriasis. They secrete proinflammatory cytokines, including IL-17 and IL-22, which propagate inflammation, recruit immune cells, and promote keratinocyte proliferation. To explore the role of CD4 + To investigate the binding affinity of T cell membrane-coated nanoparticles to IL-23, HM4M (cell membrane-coated HMS without drug loading) was prepared to eliminate the interference of the two drugs. In vitro IL-23 binding assays were performed, such as Figure 3 As shown in A, this involved incubating different nanoparticles with serum from psoriatic mice overexpressing IL-23, an approach that allowed the evaluation of IL-23 depletion and its effects on cell function and molecular dynamics. Figure 3 As shown in B, after serum incubation, HM4M showed significant efficacy in depleting IL-23. In addition, compared with cells treated with IL-23 antibody blocker or HMS, the cell viability of keratinocytes treated with HM4M was greatly reduced, and IL-23 was also significantly downregulated ( Figure 3 C and Figure 3 D), therefore, the IL-23 binding ability of HM4M is related to its CD4 + T cell membrane coating, namely CD4 + Nanoparticles disguised as T cell membranes can compete with IL-23 and prevent it from binding to CD4 + T cell interactions, suppressor CD4 + T cells differentiate into Th17 cells and inhibit the production of inflammatory cytokine IL-17 and the proliferation of keratinocytes.

[0089] Test Example 3 The therapeutic effect of HMDC4M on psoriasis in mice

[0090] A psoriasis-like mouse model was established by inducing imiquimod (IMQ) cream to verify the therapeutic effect of HMDC4M prepared in Example 1 on psoriasis lesions. The mice were randomly divided into five groups, and all treatment strategies were continued for eight days ( Figure 4 A). All mouse groups experienced negligible weight loss throughout the treatment period, suggesting that all treatment modalities had minimal adverse effects in vivo ( Fig.10On the eighth day, the PBS and HMS groups were very similar to human disease phenotypes, with a rapid increase in Psoriasis Area and Severity Index (PASI) scores, such as thickening of the stratum corneum, erythema, and scaling ( Figure 4 B and 4C). The HMS group had no significant effect on the lesion area, indicating that the nanocarrier HMS itself cannot inhibit psoriasis. No significant therapeutic effect was observed in the DAC+CPB treatment, which may be due to their insufficient targeting of the lesion site and low absorption / permeability of the skin tissue, resulting in low drug utilization. HM4M significantly reduced the PASI index on day 8 to 6.4±1.1 (P<0.05), indicating that this CD4 + T cell membrane-coated nanoparticles have a specific therapeutic effect on psoriasis. The therapeutic effect of HMDC4M was the most significant, and psoriasis lesions returned to normal, reaching a level comparable to normal skin. Psoriasis lesions were qualitatively monitored using histological methods. Histopathological analysis showed that HMDC4M could effectively reverse IMQ-induced epidermal hyperplasia, acanthosis, and hyperkeratosis ( Figure 4 D to Figure 4 F). Compared with other groups, the epidermal thickness of the HMDC4M group was significantly reduced. PCNA staining showed that HMDC4M could inhibit the level of epidermal hyperplasia, indicating that it has a stronger inhibitory effect on cell proliferation. Splenomegaly is one of the pathological characteristics of psoriasis. Compared with other groups, HMDC4M can most significantly inhibit the splenomegaly of psoriasis mice and significantly reduce the infiltration of leukocytes in the spleen ( Figure 4 G and Figure 4 H).

[0091] Normal mice were treated with high-dose HMDC4M for 30 days to evaluate the potential in vivo toxicity of HMDC4M. No significant difference in body weight was observed between the drug-treated group and the PBS group ( Fig.11 Comprehensive hematological analysis and blood biochemical data from peripheral blood showed no significant differences between the HMDC4M-treated group and the control group (as shown in Tables 1 and 2). H&E staining showed no difference between the groups ( Fig.12 After incubating red blood cells with different concentrations of HMDC4M at 37°C for 48 hours, no obvious hemolysis was observed ( Fig.13 ). These findings suggest that HMDC4M can significantly inhibit the development of psoriasis in an IMQ-induced psoriasis-like mouse model with minimal systemic toxicity.

[0092] Table 1 Blood biochemical analysis of healthy mice treated with PBS or 100 μg / mL HMDC4M 30 days after treatment (n=3)

[0093]

[0094]

[0095] Table 2 Hematological analysis of healthy mice treated with PBS or 100 μg / mL HMDC4M 30 days after treatment (n=3)

[0096] Hematological analysis PBS HMDC4M <![CDATA[WBC(×10 9 / L)]]> 8.8±1.3 8.2±1.9 <![CDATA[RBC(×10 12 / L)]]> 7.5±1.2 8.2±2.7 MCV(fl) 57.3±7.1 59.1±3.3 <![CDATA[PLT(×10 9 / L)]]> 564.6±19.3 568.6±24.2 MCH(pg) 17.6±1.2 18.1±2.2

[0097] Test Example 4: HMDC4M vs. CD4 + Regulatory mechanisms of T cells

[0098] In vitro experiments showed that CD4 + T cell membrane-coated nanoparticles can inhibit CD4 + T cells differentiate into Th17 cells, thereby inhibiting the production of inflammatory cytokine IL-17 and the proliferation of keratinocytes. + The proliferation and differentiation of T cells and the production of inflammatory cytokines by differentiated cells (such as Th17) are also regulated by epigenetic mechanisms. + T cells, intervene in T cell-mediated inflammatory diseases. CBP30 is a highly selective histone acetyltransferase inhibitor that inhibits the binding of p300 and acetylated histone H3K56 to the IL-17 gene site in Th17 cells, leading to IL-17 downregulation and inhibition of Th17 response. In psoriasis, T cells show higher levels of DNA methylation, especially in the promoter region. DNA methylation inhibitors can reduce the methylation of genes associated with psoriasis, thereby reducing CD4 + T cell differentiation and increased cell apoptosis. In addition, DNA methylation inhibitors can induce apoptosis of keratinocytes from patients with psoriasis by inhibiting the methylation of the Wnt inhibitory factor 1 (WIF1) gene. Therefore, we hypothesized that HMDC4M could be involved in the apoptosis of keratinocytes from patients with psoriasis through CD4 + The dual epigenetic drugs loaded on T cell membranes synergistically inhibited the IL-23 and IL-17 signaling pathways, thereby inhibiting psoriasis. As expected, in the IMQ-induced psoriasis-like mouse model, we observed a significant decrease in DNA methylation and H3K56Ac levels in psoriatic skin due to the dual epigenetic drugs ( Figure 5 A. Figure 5 C and Figure 5 D). HMDC4M prepared in Example 1 can significantly inhibit the expression of Th17 cells (CD4 + IL-17 + ) Figure 5 B and 5E), the secretion levels of IL-23 and IL-17 in serum were the lowest ( Figure 5 F and Figure 5 G).

[0099] 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 bionic nanocomposite material, characterized in that: The bionic nanocomposite material includes hollow mesoporous silica particles; The hollow mesoporous silica particles include a shell layer and an internal cavity; A plurality of mesopores are distributed on the shell layer; The internal cavity and mesopores are loaded with decitabine and SGC-CBP30; The hollow mesoporous silica particles are coated with CD4 + T cell membrane.

2. The biomimetic nanocomposite material according to claim 1, characterized in that: The loading amount of decitabine in the hollow mesoporous silica particles is 0.45% to 2.2%; Preferably, the loading amount of SGC-CBP30 in the hollow mesoporous silica particles is 0.51% to 2.5%.

3. The biomimetic nanocomposite material according to claim 1, characterized in that: The weight ratio of decitabine to SGC-CBP30 is 1:0.2-5.

4. The biomimetic nanocomposite material according to claim 1, characterized in that: Hollow mesoporous silica particles loaded with decitabine and SGC-CBP30 and CD4 + The volume ratio of T cell membrane is 1:0.5~1.

5.

5. The biomimetic nanocomposite material according to claim 1, characterized in that: The particle size of the hollow mesoporous silica particles is 92 to 104 nm; Preferably, the CD4 + The thickness of T cell membrane is 4 to 6 nm.

6. The biomimetic nanocomposite material according to claim 1, characterized in that: The zeta potential of the bionic nanocomposite material is 11.7-17.1 mV.

7. The method for preparing the bionic nanocomposite material according to any one of claims 1 to 6, characterized in that: The steps include: S1, respectively obtain hollow mesoporous silica particles, CD4 + T cell membrane; S2, mixing the dimethyl sulfoxide aqueous solution containing decitabine and SGC-CBP30 with the suspension containing hollow mesoporous silica particles, and stirring to obtain hollow mesoporous silica particles loaded with decitabine and SGC-CBP30; S3, hollow mesoporous silica particles containing decitabine and SGC-CBP30 were mixed with CD4 + The mixed solution of T cell membrane is extruded to obtain the bionic nanocomposite material.

8. The preparation method according to claim 7, characterized in that: In step S2, the weight ratio of decitabine, SGC-CBP30, and hollow mesoporous silica particles is (0.01-1): (0.01-1): 1; Preferably, in step S2, the stirring conditions include: stirring time is 18 to 24 hours; Preferably, in step S3, the extrusion conditions include: extrusion 25 to 35 times.

9. The preparation method according to claim 7, characterized in that: In step S1, the preparation method of the hollow mesoporous silica particles is: using solid silica balls as a template, synthesizing hollow mesoporous microspheres by hard template etching method, mixing the hollow mesoporous microspheres with 3-aminopropyltriethoxysilane solution, stirring, forming amino functional groups on the surface of the hollow mesoporous microspheres, and obtaining the hollow mesoporous silica particles; Preferably, in step S1, the CD4 + The method for preparing T cell membrane is as follows: TM Mouse CD4 + T cell isolation kit (STEMCELL TM ) Isolation of CD4 from mouse spleen + T cells.

10. Use of the bionic nanocomposite material according to any one of claims 1 to 6 in the preparation of a drug for treating psoriasis.

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