Targeted vcam1 endothelial cell self-assembled polypeptide nano-material and application thereof in xenotransplantation

Abstract

The invention provides a vcam1 endothelial cell targeting self-assembled polypeptide nano material and application thereof in xenotransplantation, and belongs to the technical field of preparation of biomedical materials. The invention relates to a self-assembled polypeptide nano material targeting VCAM1. The self-assembled polypeptide nano material is prepared from the following raw materials: polypeptide targeting VCAM1, self-assembled peptide and fatty acid, the self-assembly peptide is respectively connected with the connecting polypeptide WP1 and the fatty acid through amido bonds. The self-assembled polypeptide nanometer material targets VCAM1 through polypeptide, precise endothelial cell delivery is achieved, a layer of stable endothelial cell reconstruction protective physical barrier is formed, meanwhile, the self-assembled polypeptide nanometer material and an immunosuppressive agent are combined for use, damage of immunoreaction to endothelial cells can be effectively reduced, the integrity of the endothelial cells is maintained, and the self-assembled polypeptide nanometer material has the advantages of being high in immunosuppressive activity, high in immunosuppressive activity and the like. The immunoreaction in the organ transplantation process is inhibited, and an effective means is provided for xenogeneic organ transplantation.

Description

Technical Field

[0001] This invention belongs to the field of biomedical material preparation technology, specifically relating to a self-assembled polypeptide nanomaterial targeting vcam1 endothelial cells and its application in xenotransplantation. Background Technology

[0002] Cardiac xenotransplantation (CXTx) has emerged as a promising solution to the severe shortage of donor hearts; however, immune-mediated endothelial injury remains a key bottleneck limiting long-term graft survival. Endothelial cells (ECs), as the first interface between circulating immune cells and the transplanted organ, play a crucial role in maintaining vascular homeostasis, preventing thrombosis, and regulating immunity. Compared to allogeneic transplantation, endothelial cells in xenotransplantation face more severe challenges: in addition to classic ischemia-reperfusion injury and alloimmune responses, they must also overcome the strong innate immune activation caused by species-specific molecular incompatibility. Despite advancements in gene multiplexing technology and combined immunosuppressive strategies, complete prevention of endothelial cell injury remains unachieved, making the development of endothelial protection strategies for xenografts crucial.

[0003] Rapidly degrading endothelial cells after xenografting expose adhesion molecules such as VCAM1, triggering a pro-inflammatory cascade and recruiting innate immune cells to accelerate the rejection process. Traditional immunosuppressants such as mycophenolate mofetil (MMF) can inhibit T cell responses, but they cannot address the inherent fragility of xenograft endothelium and may even impair endothelial repair mechanisms. Summary of the Invention

[0004] In view of this, the purpose of this invention is to provide a self-assembled polypeptide nanomaterial that targets VCAM1, which can not only effectively inhibit the immune response during organ transplantation and protect endothelial cells, but also reduce the damage of the immune response to endothelial cells and maintain the integrity of endothelial cells.

[0005] This invention provides a self-assembled peptide nanomaterial targeting VCAM1, which is prepared from the following raw materials: a peptide targeting VCAM1, a self-assembled peptide, and a fatty acid;

[0006] The self-assembled peptide is linked to the polypeptide and fatty acid via amide bonds, respectively.

[0007] The amino acid sequence of the peptide targeting VCAM1 is shown in SEQ ID NO:1.

[0008] Preferably, the fatty acid includes lauric acid (C12).

[0009] Preferably, the amino acid sequence of the self-assembled peptide is shown in SEQ ID NO: 2.

[0010] Preferably, the structural formula is shown in Formula I:

[0011]

[0012] This invention provides a method for preparing the self-assembled peptide nanomaterial, which is prepared by solid-phase synthesis using peptides targeting VCAM1, self-assembled peptides, and fatty acids as raw materials.

[0013] Preferably, the molar ratio of the VCAM1-targeting peptide, the self-assembled peptide, and the fatty acid is (0.8–1.2):(0.8–1.2):(1.8–2.2).

[0014] This invention provides a composition in which the active ingredients include an immunosuppressant and the self-assembled peptide nanomaterial or the self-assembled peptide nanomaterial prepared by the preparation method;

[0015] The mass ratio of the immunosuppressant to the self-assembled peptide nanomaterial is 0.7–1.2:0.7–1.2.

[0016] This invention provides the application of the self-assembled peptide nanomaterial, the self-assembled peptide nanomaterial prepared by the preparation method, or the composition thereof in the preparation of products that inhibit immune rejection in xenotransplantation.

[0017] Preferably, the xenotransplantation includes xenotransplantation of the heart.

[0018] Preferably, the method of inhibiting immune rejection in xenotransplantation is that the self-assembled polypeptide nanomaterial targets VCAM1 in vascular endothelial cells of xenotransplanted organs, protecting endothelial cells and reducing damage caused by immune responses.

[0019] Preferably, the dosage form of the product includes injectable dry powder and / or injectable solution.

[0020] This invention provides a self-assembled peptide nanomaterial targeting VCAM1, prepared from the following raw materials: a VCAM1-targeting peptide, a self-assembled peptide, and a fatty acid; the self-assembled peptide is linked to the peptide and fatty acid respectively via amide bonds; the amino acid sequence of the VCAM1-targeting peptide is shown in SEQ ID NO:1. The self-assembled peptide nanomaterial of this invention maintains cell integrity and prevents immune cell infiltration, preserving the integrity of endothelial cells, thereby protecting vascular endothelial cells and inhibiting the immune response during xenotransplantation, providing significant support for xenotransplantation. Attached Figure Description

[0021] Figure 1 The images show the distribution of endothelial cell subsets (A) and cell proportions (B) in single-cell sequencing of myocardial tissue in Example 1.

[0022] Figure 2 This is a diagram of characteristic genes highly expressed in the four endothelial cell subsets in Example 1;

[0023] Figure 3 Immunofluorescence staining images of VCAM1 positive cells in the control group and xenograft group in Example 1;

[0024] Figure 4 The graph shows the molecular structure of WP1 in Example 2 (A) and the results of electrospray ionization mass spectrometry detection (B).

[0025] Figure 5 This is a graph showing the high-performance liquid chromatography (HPLC) detection results of WP1 in Example 2;

[0026] Figure 6 The graph shows the molecular structure of WP2 in Example 2 (A) and the results of electrospray ionization mass spectrometry detection (B).

[0027] Figure 7 This is a graph showing the high-performance liquid chromatography (HPLC) detection results of WP2 in Example 2;

[0028] Figure 8 The TEM images of WP1 and WP2 in Example 3 are shown, with a scale bar of 200 nm.

[0029] Figure 9 The images show the DLS detection data of WP1 and WP2 at different time points in Example 3.

[0030] Figure 10 The retention time curve of WP1 on the surface of HUVEC cells in Example 4;

[0031] Figure 11 This is a line graph showing the transmittance of FITC-labeled BSA in Example 4;

[0032] Figure 12 This is a CLSM diagram of the interaction between WP1 and HUVEC cells in Example 5, with a scale bar of 10 μm;

[0033] Figure 13 This is a SEM image of the interaction between WP1 and HUVEC cells in Example 5;

[0034] Figure 14 This is a flowchart of the mouse heart transplantation process involving WP1 intervention in Example 6;

[0035] Figure 15The following are the post-transplant survival curves for the control group, WP1 group, MMF group, and MMF+WP1 group in Example 6. "**" indicates a significant difference (P < 0.01).

[0036] Figure 16 The images show the hematologic and immune cell infiltration (H&E) data of myocardial tissue in the control group, WP1 group, MMF group, and MMF+WP1 group in Example 6. "**" and "***" indicate significant differences (P < 0.01 and P < 0.001, respectively). Detailed Implementation

[0037] This invention provides a self-assembled peptide nanomaterial targeting VCAM1, which is prepared from the following raw materials: a peptide targeting VCAM1, a self-assembled peptide, and a fatty acid; the self-assembled peptide is linked to the linking peptide WP1 and the fatty acid respectively via amide bonds; the preferred amino acid sequence of the peptide is shown in SEQ ID NO:1 (VHPKQHRGGSKGC).

[0038] In this invention, the VCAM1-targeting polypeptide can effectively target and bind to the VCAM1 protein in vascular endothelial cells. Experiments of this invention have demonstrated that the number of vascular endothelial cells expressing the VCAM1 protein is significantly reduced in cardiac tissue after xenograft heart transplantation. Therefore, successful xenograft organ transplantation can be achieved by protecting vascular endothelial cells expressing the VCAM1 protein.

[0039] In this invention, the fatty acid preferably includes lauric acid (C12). The fatty acid has strong hydrophobicity, providing hydrophobic groups for the target experimental molecule (WP), which is beneficial for promoting the formation of nanostructures.

[0040] In this invention, the amino acid sequence of the self-assembled peptide is preferably as shown in SEQ ID NO: 2 (FFVDF). The function of the self-assembled peptide is to connect the peptide targeting VCAM1 and the fatty acid.

[0041] In one embodiment of the present invention, when the fatty acid is lauric acid C12, the preferred structural formula of the self-assembled polypeptide nanomaterial is as shown in Formula I:

[0042]

[0043] In one embodiment of the present invention, experiments were conducted at the endothelial cell level. Results showed that the self-assembled polypeptide nanomaterial WP1, through its VCAM1-targeting polypeptide binding to VCAM1 in vascular endothelial cells, prolonged the endothelial cell half-life to 8.8 hours. Furthermore, the binding of WP1 did not affect the function of transendothelial protein channels, ensuring that endothelial cell function remained unaffected. Confocal laser scanning microscopy and scanning electron microscopy revealed that WP1 not only exhibited good binding ability to VCAM1, but also that the cell surface WP1 underwent structural transformation, i.e., the nanoparticles transformed into fibers through receptor-ligand interaction. In in vivo experiments, it effectively inhibited the immune response during organ transplantation, achieving a protective effect on endothelial cells, reducing damage to endothelial cells from the immune response, and maintaining the integrity of endothelial cells.

[0044] This invention provides a method for preparing the self-assembled peptide nanomaterial, which is prepared by solid-phase synthesis using peptide WP1, self-assembled peptide and fatty acid as raw materials.

[0045] In this invention, the preferred molar ratio of the VCAM1-targeting peptide, the self-assembled peptide, and the fatty acid is 0.8–1.2:0.8–1.2:1.8–2.2, and can be 1:1:2. This invention does not impose any particular limitation on the method for preparing the self-assembled peptide nanomaterial using the solid-phase synthesis technique; any synthesis method well-known in the art can be used. In this embodiment, the self-assembled peptide nanomaterial WP1 was synthesized by Suzhou Hanno Biotechnology Co., Ltd.

[0046] The present invention provides a composition in which the active ingredients include an immunosuppressant and the self-assembled peptide nanomaterial or the self-assembled peptide nanomaterial prepared by the preparation method; the mass ratio of the immunosuppressant to the self-assembled peptide nanomaterial is 0.7-1.2:0.7-1.2, or can be 1:1.

[0047] In this invention, the mass ratio of the immunosuppressant to the self-assembled peptide nanomaterial can be 0.8–1.2:0.8–1.2, or 1:1. The immunosuppressant is preferably mycophenolate mofetil. Compared with single-drug administration, the combined use of the immunosuppressant and the self-assembled peptide nanomaterial is more effective in protecting the integrity of endothelial cells, ensuring their tight attachment to the vascular lumen, and reducing immune cell infiltration.

[0048] This invention provides the application of the self-assembled peptide nanomaterial, the self-assembled peptide nanomaterial prepared by the preparation method, or the composition thereof in the preparation of products that inhibit immune rejection in xenotransplantation.

[0049] In this invention, the xenotransplantation preferably includes xenotransplantation of the heart. The preferred method for inhibiting immune rejection of xenotransplantation is that the self-assembled polypeptide nanomaterial targets VCAM1 in the vascular endothelial cells of the xenotransplantation organ, protecting the endothelial cells and reducing damage caused by the immune response.

[0050] In this invention, the product is preferably a pharmaceutical product. The dosage form of the pharmaceutical product preferably includes injectable dry powder and / or injectable solution. In the injection, the concentration of the self-assembled polypeptide nanomaterial is 0.8 mg / mL or higher, and can be 1 mg / mL. This invention does not impose any particular limitation on the preparation method of the product; any preparation method well-known in the art can be used.

[0051] The following detailed description, in conjunction with embodiments, illustrates a targeted VCAM1 endothelial cell self-assembly polypeptide nanomaterial provided by the present invention and its application in xenografting. However, these descriptions should not be construed as limiting the scope of protection of the present invention.

[0052] Example 1

[0053] To investigate the characteristics of endothelial cells that are easily damaged in xenotransplantation of the heart, this embodiment first constructed a large animal model of xenotransplantation from pig to macaque, and performed single-cell sequencing on the transplanted heart. The specific steps were as follows: the donor heart was transplanted into the recipient's peritoneal cavity using a xenotransplantation method. After ultrasound detection showed that the graft had lost function, the heart was harvested for single-cell sequencing of myocardial tissue and normal control myocardial tissue.

[0054] The results are as follows Figures 1-3 As shown. Among them. Figure 1 Figure (A) shows the endothelial cell clustering results in normal control and transplanted myocardial tissue, and figure (B) shows the endothelial cell proportion. Figure 2 for Figure 1 Genes highly expressed in each of the four endothelial cell groups in China. Figure 3 Immunofluorescence staining images of VCAM1 in the heart are shown for normal controls and after xenograft. Cell proportion analysis revealed that the proportion of endothelial cell subset 3 was significantly reduced after xenograft compared to the normal control group. Figure 1(B) This indicates that endothelial cell subpopulation 3 requires protection. Analysis of the gene expression characteristics of endothelial cell subpopulation 3 revealed that the highly expressed membrane protein is VCAM1. Other genes highly expressed in endothelial cell subpopulation 3 are not membrane proteins (non-membrane proteins cannot be specifically recognized and attached by nanomaterials to form nanofiber structures), or they are also highly expressed in endothelial cell subpopulations 1, 2, and 4 (making specific protection of endothelial cell subpopulation 3 impossible), and therefore were not further investigated. Compared to normal control hearts, the number of endothelial cells expressing VCAM1 was significantly reduced after xenograft heart transplantation. In conclusion, VCAM1 was selected as the target for endothelial protection for validation and subsequent preparation of targeted nanomaterials.

[0055] Example 2

[0056] A method for preparing an endothelial protective peptide

[0057] The peptide C12-FFVDF-VHPKQHRGGSKGC(WP1) and the negative control molecule C12-FFVDF-GCHPGSVKRGQHK(WP2) were prepared using solid-phase synthesis technology and synthesized by Fmoc solid-phase synthesis.

[0058] WP1 and WP2 were characterized by high-performance liquid chromatography (HPLC) and electrospray ionization (ESI) mass spectrometry, and the results are as follows: Figures 4-7 As shown. By Figures 4-7 It can be concluded that WP1 and WP2 were successfully prepared.

[0059] Example 3

[0060] To evaluate the potential of WP1 as an endothelial protective peptide, this embodiment presents a detailed analysis of the self-assembled nanostructure of WP1.

[0061] By adding the VCAM1 extracellular receptor protein (VCAM1 protein), expression was achieved in human umbilical vein endothelial cells (HUVECs, purchased from the Cell Culture Center of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences), transforming nanoparticles into nanofibers, and then culturing them at 37°C for several hours. Specifically, HUVECs in DMEM medium were co-incubated at room temperature with WP1, VCAM1 protein, and DMEM medium. The amount of VCAM1 protein added was 1 / 10 of the amount of WP1. Samples were prepared at 0, 2, and 4 hours. The co-incubation solution was used to measure the size (DLS, Nano ZS, Malvern) and perform transmission electron microscopy (Philips CM-120TEM, USA). TEM samples were stained with uranium acetate.

[0062] TEM results showed that the diameters of WP1 and WP2 were approximately 10 nm at 0 h, gradually increasing to 20 nm. Nanofiber structures with a diameter of approximately 9 nm were observed. The number of nanofibers increased within 2 h, and the nanofiber network was clearly visible after 4 h, exhibiting a wide size distribution. Figure 8 DLS measurements showed the distribution size of WP1 and WP2 aggregates. Figure 9 This study confirmed the structural transformation of WP1 from nanoparticles to nanofibers, while WP2 did not undergo a morphological transformation. These results indicate that WP1 possesses a stable nanostructure.

[0063] Example 4

[0064] Dissolve 3 mg of WP1 in 3 mL of PBS buffer, then add 1 / 10 molar of Dil (1 mL), and add an appropriate amount of triethylamine. Adjust the pH to 9.4°C and stir overnight in an ice bath. The reaction solution turns fluorescent blue. Then dialyze through a dialysis bag with a molecular weight of 1000 Diatoms, changing the water every 1 hour, for 2 days. Freeze-dry the obtained residue to obtain WP1 labeled with Dil for later use.

[0065] WP1 labeled with Dil was perfused into mouse donor hearts at a flow rate of 2 mL for transplantation experiments. Small animal fluorescence imaging was performed at different time points, and the half-life was subsequently calculated from the fluorescence signal.

[0066] The results are as follows Figure 10 As shown, by Figure 10 It can be concluded that WP1 has a half-life of up to 8.8 hours on the surface of endothelial cells.

[0067] HUVEC cells with 60%–80% confluence were treated with trypsin at a concentration of 100,000 cells / cm³. 2 The inoculation rates were respectively inoculated into TNF-α (TNF-α, purchased from Abcam, CAS: 94948-59-1, 2000 U / mL), WP1 (WP1, 50 μM), WP2 (WP2, 50 μM), and WP1+TNF (WP1, 50 μM, TNF-α 2000 U / mL) (3 μm pore size, 0.33 cm). 2 Surface area) or WP2+TNF (WP2, 50 μM, TNF-α 2000 U / mL) (3 μm pore size, 0.33 cm 2 The tissue culture inserts (3415, Corning) were incubated at 37°C and 5% CO2 for 3 hours, with a blank control group included. The tissue culture inserts were placed in 24-well plates. HUVEC cells were allowed to grow in the tissue culture inserts for 1 week before performing transendothelial protein channel experiments, with the cell culture medium changed every 2 days.

[0068] Transendothelial protein channel assays were performed using FITC-labeled BSA (A92771, Sigma). HUVEC cell monolayers cultured under different conditions were passaged for 3 hours in medium containing FITC-labeled BSA. First, the medium in both compartments was replaced with serum-free medium for 1 hour. Then, medium containing 0.5 mg / mL FITC-labeled BSA was added to the upper compartment, and medium containing 0.5 mg / mL unlabeled BSA (A-7888, Sigma) was added to the lower compartment. Over 3 hours, 100 μL aliquots were collected hourly from the lower compartment and replaced with medium containing 0.5 mg / mL unlabeled BSA. The fluorescence signal of the collected medium was recorded, and the concentration was calculated based on the FITC-labeled BSA standard curve.

[0069] The results are as follows Figure 11 As shown. By Figure 11 It can be concluded that WP1 does not affect the passage of BSA through endothelial cells.

[0070] Example 5

[0071] CLSM and SEM were used to verify the structural transformation of WP1 on the cell surface, and the steps were as follows:

[0072] HUVEC cells were cultured in glass dishes for 12 hours. WP1 (50 μM) was incubated with cells in DMEM at 37°C for 6 or 12 hours, with AC16 cells as a control. For confocal laser scanning microscopy (CLSM, LSM 800, ZEISS), samples were fixed with glutaraldehyde (4%) for 10 minutes, washed three times with PBS, and examined using a 405 nm laser and a 40× immersion objective.

[0073] To further verify the binding of WP1 to VCAM1, this invention used a rabbit anti-VCAM1 (Abcam, USA) monoclonal antibody (Sigma-Aldrich, USA) to detect the extracellular domain of VCAM1 on the surface of HUVECs. Specifically, the rabbit anti-VCAM1 monoclonal antibody was co-incubated with the aforementioned HUVEC cells bound to WP1 in DMEM medium at 5% CO2 and 37°C. For scanning electron microscopy (SEM, Philips XL30 TMP, FEI, Hillsborough), the cells were fixed overnight with glutaraldehyde (4%) and then gold-plated for 2 minutes. Figure 13 As shown in the figure, the first three icons have a ruler of 20μm, and the last icon has a ruler of 5μm.

[0074] Depend on Figure 12 and Figure 13It can be concluded that WP1 has a good binding ability with VCAM1, and that WP1 on the cell surface can achieve structural transformation.

[0075] Example 6

[0076] To further evaluate the protective effect of WP1 on endothelial cells (ECs) in vivo, four mouse heart transplantation (HTx) models were constructed in this embodiment: control group, WP1 group, MMF group and MMF+WP1 group.

[0077] Control group: 2 mL of PBS solution was infused into the donor heart via the inferior vena cava;

[0078] WP1 group: 2 mL of PBS solution containing WP1 was perfused into the donor heart via the inferior vena cava. The final concentration of WP1 in the PBS solution was 1 mg / mL.

[0079] Mycophenolate mofetil (MMF) group: 2 mL of PBS solution containing MMF was perfused into the donor heart via the inferior vena cava. The final concentration of MMF in the PBS solution was 1 mg / mL.

[0080] MMF+WP1 group: 2 mL of PBS solution containing WP1 and MMF was perfused into the donor heart via the inferior vena cava. The final concentration of WP1 in the PBS solution was 1 mg / mL, and the final concentration of MMF in the PBS solution was 1 mg / mL.

[0081] The mouse heart transplantation protocol was based on the cervical heterotopic transplantation model (J Vis Exp. 2014 Oct12; (92):e50753). In short, a mouse heterotopic heart transplantation model was constructed using BALB / c (H-2d) and C57BL / 6 (H-2b) mice (6-8 weeks old). C57BL / 6 mice were anesthetized and placed supine. After preparing the skin, layers were incised to expose and release the left external jugular vein and common carotid artery. The vessels were then cut, slid onto specially designed cannulas, and secured with sutures. Under deep anesthesia, the thoracic cavity of the BALB / c mice was opened, and the ascending aorta and pulmonary trunk of sufficient length were cut. The remaining vessels were ligated and cut sequentially, and the heart was removed. The donor heart was placed in the recipient's neck, and the aorta was connected to the common carotid artery, and the pulmonary trunk to the external jugular vein, all with sutures. The skin was then sutured, and the mice were placed in a warm environment for recovery. All model mice were housed in an SPF environment with ample food and water. Flowchart as follows: Figure 14 As shown.

[0082] Survival was monitored in all groups by visual inspection and palpation. Kaplan-Meier analysis was performed to compare the protective effect of WP1 on heart grafts. Results showed that the median survival time in the WP1 and WP1+MMF groups was 12.1 days and 27 days, respectively. Compared with the control group, the WP1 group showed an increased graft survival time (in... Figure 15 In the diagram, PBS represents the control group.

[0083] To further evaluate the protective effect of WP1+MMF on endothelial cells, mouse heart grafts were obtained from the control group, WP1 group, MMF group, and WP1+MMF group 3 days after surgery. The first 3 days are the period of most severe endothelial injury after heart transplantation, and early endothelial protection is crucial for heart grafts. Routine HE pathological examination was performed, and staining for T cell and macrophage surface markers CD3 (ZA-0503, zsbio) and CD68 (ZM-0060, zsbio) was performed to assess endothelial integrity and the degree of myocardial inflammatory infiltration. In the control group, significant endothelial swelling and detachment were observed due to IRI and immune damage, while the endothelium in the WP1+MMF group remained intact and tightly attached to the vascular lumen. Simultaneously, the WP1+MMF group showed less immune cell infiltration than the control group. Figure 16 ).

[0084] As can be seen from the above embodiments, the endothelial protective peptide material of the present invention can effectively inhibit the immune response during organ transplantation, thereby protecting endothelial cells, reducing the damage of the immune response to endothelial cells, and maintaining the integrity of endothelial cells.

[0085] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A self-assembled peptide nanomaterial targeting VCAM1, characterized in that, It is prepared from the following raw materials: peptides targeting VCAM1, self-assembled peptides, and fatty acids; The self-assembled peptide is linked to the polypeptide and fatty acid via amide bonds, respectively. The amino acid sequence of the peptide targeting VCAM1 is shown in SEQ ID NO:

1.

2. The self-assembled polypeptide nanomaterial according to claim 1, characterized in that, The fatty acid includes lauric acid C12; The amino acid sequence of the self-assembled peptide is shown in SEQ ID NO:

2.

3. The self-assembled polypeptide nanomaterial according to claim 1, characterized in that, The structural formula is shown in Formula I:

4. A method for preparing the self-assembled polypeptide nanomaterial according to any one of claims 1 to 3, characterized in that, It was prepared by solid-phase synthesis using peptides targeting VCAM1, self-assembled peptides, and fatty acids as raw materials.

5. The preparation method according to claim 4, characterized in that, The molar ratio of the peptide targeting VCAM1, the self-assembled peptide, and the fatty acid is (0.8–1.2):(0.8–1.2):(1.8–2.2).

6. A composition, characterized in that, The active ingredients include immunosuppressants and the self-assembled polypeptide nanomaterials according to any one of claims 1 to 4 or the self-assembled polypeptide nanomaterials prepared by the preparation method according to claim 4 or 5; The mass ratio of the immunosuppressant to the self-assembled peptide nanomaterial is 0.7–1.2:0.7–1.

2.

7. The use of the self-assembled polypeptide nanomaterial according to any one of claims 1 to 3, the self-assembled polypeptide nanomaterial prepared by the preparation method according to claim 4 or 5, or the composition according to claim 6 in the preparation of a product that inhibits immune rejection in xenotransplantation.

8. The application according to claim 7, characterized in that, Xenotransplantation includes xenotransplantation of the heart.

9. The application according to claim 7, characterized in that, The method of inhibiting immune rejection in xenotransplantation is that the self-assembled polypeptide nanomaterial targets VCAM1 in vascular endothelial cells of xenotransplanted organs, protecting endothelial cells and reducing damage caused by immune responses.

10. The application according to any one of claims 7 to 9, characterized in that, The dosage forms of the product include injectable dry powder and / or injectable solution.

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