Self-assembled polypeptide, self-assembled polypeptide nano-material as well as preparation method and application of self-assembled polypeptide nano-material

Abstract

The invention discloses a self-assembled polypeptide, a self-assembled polypeptide nano-material as well as a preparation method and application of the self-assembled polypeptide nano-material. The sequence of the self-assembled polypeptide is SRNLIDK [C14] ATGPAK [C14] DILNRS. The preparation method of the self-assembled polypeptide nano material comprises the following steps: dissolving self-assembled polypeptide in deionized water or a PBS (Phosphate Buffer Solution), and incubating; adding a hydrophobic anti-fibrosis drug solution into the incubated solution, and carrying out ultrasonic treatment; and then incubating to form a nano spherical skin-core structure of the self-assembled polypeptide coated hydrophobic anti-fibrosis drug. The self-assembled polypeptide nano material can be applied to preparation of medicines for resisting organ or tissue fibrosis. A plurality of PDGFR beta binding sites exist in the self-assembled polypeptide and can be specifically bound with PDGFR beta protein, so that it is guaranteed that the entrapped anti-fibrosis medicine is bound to activated hepatic stellate cells with high expression of PDGFR beta in a targeted mode, meanwhile, the polypeptide modifies an FAP-alpha response sequence, and the anti-fibrosis medicine can be responsively and specifically released in an FAP-alpha high expression area.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials, and specifically relates to a self-assembling polypeptide, a self-assembling polypeptide nanomaterial, and a preparation method and application thereof. Background Art

[0002] Liver fibrosis is the terminal stage of many chronic liver diseases and may develop into liver failure or even liver cancer. Quiescent hepatic stellate cells differentiate into activated hepatic stellate cells (aHSCs), which then transdifferentiate into myofibroblasts, producing profibrotic cytokines and excessive extracellular matrix, which is the main cause of liver fibrosis. Currently, there are no FDA-approved drugs for patients with liver fibrosis. In addition, the literature "TANG R, LI R, LI H, et al. Design of Hepatic Targeted Drug Delivery Systems for Natural Products: Insights into Nomenclature Revision of Nonalcoholic Fatty Liver Disease [J]. ACS Nano, 2021, 15 (11): 17016-46." points out that anti-fibrotic drugs lack tissue, organ and cell targeting. Various problems arising in the clinical treatment of liver fibrosis urgently need to improve the clinical efficacy of drugs, or develop new fibrosis treatment drugs and treatment strategies. Self-assembling peptide nanomaterials refer to biomaterials in which peptide molecules of a specific sequence spontaneously assemble to form nanostructures under the action of non-covalent bonds. Existing research data has not reported any research on how self-assembling peptide nanomaterials can alleviate liver fibrosis by targeting proteins overexpressed in aHSCs. Summary of the invention

[0003] In view of the deficiencies in the prior art, the technical problem to be solved by the present invention is to provide a self-assembling polypeptide, a self-assembling polypeptide nanomaterial, and a preparation method and application thereof.

[0004] The technical solution of the present invention to solve the technical problem of the self-assembling polypeptide is to provide a self-assembling polypeptide, characterized in that the sequence of the self-assembling polypeptide is SRNLIDK[C 14 ]ATGPAK[C 14 ]DILNRS.

[0005] The technical solution of the present invention to solve the technical problem of the preparation method is to provide a method for preparing a self-assembling polypeptide nanomaterial, characterized in that the method comprises the following steps:

[0006] Step 1, dissolving the self-assembling polypeptide according to any one of claims 1 to 3 in deionized water or PBS solution to obtain a self-assembling polypeptide solution;

[0007] Step 2, incubating the self-assembling polypeptide solution obtained in step 1, during which the self-assembling polypeptide forms a fiber network structure, thereby obtaining an incubated self-assembling polypeptide solution;

[0008] Step 3, adding the hydrophobic anti-fibrosis drug solution to the incubated self-assembling polypeptide solution obtained in step 2, and subjecting the solution to ultrasonic treatment to break the fiber network structure and evenly wrap the hydrophobic anti-fibrosis drug molecules; and then incubating to form a self-assembling polypeptide nanomaterial with a nano-spherical skin-core structure in which the hydrophobic anti-fibrosis drug is wrapped by the self-assembling polypeptide.

[0009] The technical solution of the present invention to solve the technical problem of the self-assembling polypeptide nanomaterial is to provide a self-assembling polypeptide nanomaterial prepared by the preparation method of the self-assembling polypeptide nanomaterial.

[0010] The technical solution of the present invention to solve the application technical problem is to provide an application of the self-assembling polypeptide nanomaterial in the preparation of drugs against organ or tissue fibrosis.

[0011] Compared with the prior art, the present invention has the following beneficial effects:

[0012] (1) The present invention provides a self-assembling polypeptide having multiple PDGFRβ binding sites in its sequence, which can specifically bind to the PDGFRβ protein, thereby ensuring that the encapsulated anti-fibrosis drug is targeted to the activated hepatic stellate cells (PDGFRβ) that highly express PDGFRβ. + At the same time, the polypeptide modifies the FAP-α response sequence, which can make the anti-fibrosis drug responsive and specific in the FAP-α high expression area, thereby enhancing the accumulation and retention of anti-fibrosis drugs in fibrotic tissues, and can significantly reduce the mRNA expression and protein content of type I collagen, type III collagen, fibronectin, and α-SMA, thereby enhancing the anti-fibrosis effect of the drug.

[0013] (2) The present invention provides a self-assembling polypeptide nanomaterial, which is formed by encapsulating a hydrophobic anti-fibrosis drug in a peptide nanoshell in the form of self-assembly of a self-assembling polypeptide. The self-assembling nanomaterial is a nanoscale self-assembling nanoparticle with a spherical structure and good biocompatibility. The nanoparticle can be used as a carrier material for anti-fibrosis drugs, and can deliver the anti-fibrosis drugs to fibrotic areas in a targeted manner, and prolong the accumulation and retention of the anti-fibrosis drugs in the fibrotic areas, thereby improving the therapeutic effect of the anti-fibrosis drugs on fibrotic tissues. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 is a transmission electron microscopy image of the self-assembling polypeptide after incubation of the present invention;

[0015] Figure 2 It is a transmission electron microscope image of the self-assembling polypeptide nanomaterial of the present invention;

[0016] Figure 3 This is a graph showing the effect of the self-assembling polypeptide nanomaterials containing different concentrations of PFD on the cell activity of LX-2;

[0017] Figure 4 This is a diagram showing the effect of the self-assembling polypeptide nanomaterial of the present invention on the uptake of anti-fibrosis drugs by LX-2 cells;

[0018] Figure 5 This is a diagram showing the effect of the self-assembling polypeptide nanomaterial of the present invention on the activation of LX-2 cells;

[0019] Figure 6 These are HE staining, Masson staining, and Sirius red staining pictures of liver tissues of mice in different experimental groups of the present invention;

[0020] Figure 7 These are pictures of immunohistochemical staining (α-SMA and Fibronectin) of liver tissues of mice in different experimental groups of the present invention;

[0021] Figure 8 The diagram is a graph of mRNA levels of fibrosis marker proteins α-SMA, fibronectin, type I collagen, and type III collagen in liver tissues of mice in different experimental groups of the present invention;

[0022] Fig. 9 The diagram is a result of immunoblotting of the levels of fibrosis marker proteins α-SMA, fibronectin, and type I collagen and type III collagen in the liver tissues of mice in different experimental groups of the present invention. DETAILED DESCRIPTION

[0023] The specific embodiments of the present invention are given below. The specific embodiments are only used to further illustrate the present invention in detail and do not limit the protection scope of the present invention.

[0024] The present invention provides a self-assembling polypeptide (named as FERPep), characterized in that the sequence of the self-assembling polypeptide is SRNLIDK[C 14 ]ATGPAK[C 14 ]DILNRS.

[0025] Preferably, the structural formula of the self-assembling polypeptide is:

[0026]

[0027] Preferably, the self-assembling polypeptide is an amphipathic polypeptide comprising two SRNLID amino acid sequences, two C14 hydrocarbon tails and a FAP-α responsive sequence (ie, ATGPA amino acid sequence), the SRNLID sequence being a PDGFRβ binding site; the two SRNLID sequences are connected via the FAP-α responsive sequence.

[0028] The present invention also provides a method for preparing a self-assembling polypeptide nanomaterial (hereinafter referred to as the method), characterized in that the method comprises the following steps:

[0029] Step 1, dissolving the self-assembling polypeptide in deionized water or PBS solution to obtain a self-assembling polypeptide solution;

[0030] Preferably, in step 1, the dissolution process is: ultrasonically dissolve the polypeptide completely at a power of 150 to 200 W (preferably 150 W) for 15 to 20 min (preferably 15 min).

[0031] Preferably, in step 1, the concentration of the self-assembling polypeptide solution is 100 μg / mL to 1 mg / mL.

[0032] Preferably, in step 1, the concentration of the PBS solution is preferably 0.1 mol / L.

[0033] Step 2, incubating the self-assembling polypeptide solution obtained in step 1, during which the self-assembling polypeptide forms a fiber network structure, thereby obtaining an incubated self-assembling polypeptide solution;

[0034] Preferably, in step 2, the incubation temperature is 30-37° C. (preferably 37° C.), and the incubation time is 24-48 h (preferably 24 h).

[0035] Step 3, adding the hydrophobic anti-fibrosis drug solution to the incubated self-assembling polypeptide solution obtained in step 2, and subjecting the solution to ultrasonic treatment to break the fiber network structure and evenly wrap the hydrophobic anti-fibrosis drug molecules; and then incubating to form a nano-spherical skin-core structure of the self-assembling polypeptide wrapping the hydrophobic anti-fibrosis drug, i.e., a self-assembling polypeptide nanomaterial.

[0036] Preferably, in step 3, the concentration of the hydrophobic anti-fibrosis drug solution is 100 μM to 1 mM (preferably 100 μM), and the solvent is preferably PMSO; the volume ratio of the hydrophobic anti-fibrosis drug solution to the incubated self-assembling polypeptide solution is 1:100 to 500.

[0037] Preferably, in step 3, the hydrophobic anti-fibrotic drug is pirfenidone or nintedanib.

[0038] Preferably, in step 3, the ultrasonic process is: ultrasonication at a power of 150 to 200 W for 15 to 20 min.

[0039] Preferably, in step 3, the incubation temperature is 30-37° C., and the incubation time is 24-48 h.

[0040] The present invention also provides a self-assembling polypeptide nano material prepared by the preparation method of the self-assembling polypeptide nano material.

[0041] The present invention also provides an application of the self-assembling polypeptide nanomaterial in preparing drugs for resisting organ or tissue fibrosis.

[0042] Preferably, the organ or tissue fibrosis is liver fibrosis, kidney fibrosis or myocardial fibrosis.

[0043] Embodiment 1:

[0044] The preparation method of the self-assembling polypeptide nanomaterial comprises the following steps:

[0045] (1) Add 100 μg of self-assembling polypeptide FERPep into 1000 μL of sterile deionized water, and sonicate at a power of 150 W for 15 min to completely dissolve the polypeptide to obtain a self-assembling polypeptide solution;

[0046] (2) incubating the self-assembling polypeptide solution at 37° C. for 24 hours, during which the self-assembling polypeptide forms a fiber network structure, thereby obtaining a self-assembling polypeptide solution after incubation;

[0047] (3) Add 5 μL of 100 μM pirfenidone solution to the incubated self-assembled polypeptide solution obtained in step 2, and ultrasonicate at 150 W for 15 min to break the fiber network structure and evenly wrap the pirfenidone molecules; then incubate at 37° C. for 24 h to form a self-assembled polypeptide nanomaterial with a nano-spherical skin-core structure in which the self-assembled polypeptide wraps the pirfenidone (named PFD@ns).

[0048] Depend on Figure 1 It can be seen that the self-assembling polypeptide can self-assemble into long fibers after incubation, and can form a fiber network structure. Figure 2 It can be seen that the self-assembled polypeptide nanomaterials present a nanoscale spherical structure. Figure 1 and Figure 2 It can be seen that after the addition of hydrophobic anti-fibrotic drugs, the network nanostructure is transformed into nanospheres, and the nanospheres can specifically react with FAP-α protein, and FAP-α protein degrades the spherical nanoparticles into a network structure.

[0049] Embodiment 2:

[0050] In order to study the biocompatibility of self-assembling polypeptide nanomaterials, Example 2 conducted a CCK-8 cell proliferation experiment to test the biocompatibility of self-assembling polypeptide nanomaterials with human hepatic stellate cells (LX-2) in order to determine cell viability. The specific operation process is as follows:

[0051] (1) LX-2 cells were seeded into a 96-well plate, with approximately 5 × 103 cells per well; the 96-well plate was then placed in a CO2 incubator for 24 h;

[0052] (2) Add different concentrations of pirfenidone solution (100 nM, 200 nM) and self-assembled peptide nanomaterials containing different concentrations of pirfenidone (100 nM, 200 nM) into a 96-well plate, and then place the 96-well plate in a CO2 incubator for 24 h; set up 3 replicate wells for each concentration; and use complete medium as the control group;

[0053] (3) Add 10 μL of CCK-8 solution to each well of a 96-well plate; gently shake the plate to mix the solution thoroughly, and then place the plate in a CO2 incubator and incubate for 2 h;

[0054] (4) Take the 96-well plate out of the incubator, protect it from light, measure the optical density OD value of each well at 450 nm, and calculate the cell survival rate.

[0055] Results: Figure 3 As shown, compared with cells cultured with complete culture medium alone, the self-assembling polypeptide nanomaterials containing 100 nM and 200 nM pirfenidone had no significant effect on cell activity, demonstrating that the self-assembling polypeptide nanomaterials have good biocompatibility.

[0056] Embodiment 3:

[0057] Verification: Self-assembled peptide nanomaterials enhanced the uptake of anti-fibrotic drugs by LX-2 cells.

[0058] (1) The experiment was divided into three groups: normal group (Control, DMEM complete medium only), TGF-β1 group, and TGF-β1+PDGFRβ antibody group (TGF-β1+iAb).

[0059] (2) Move the 24-well plate to the clean bench, place the slides in the plate, and inoculate LX-2 cells into the plate, with approximately 2 × 104 cells per well; then incubate the 24-well plate in a CO2 incubator for 24 h;

[0060] (3) 10 ng / ml TGF-β was added to the TGF-β1 group and TGF-β1+iAb group to induce LX-2 cell activation, and then the 24-well plates were cultured in a cell CO2 incubator for 48 h;

[0061] (4) FITC-labeled self-assembling peptide nanomaterials were added to the TGF-β1 group and the TGF-β1+iAb group, and PDGFRβ antibody was added to the TGF-β1+iAb group at the same time, and incubated at 37°C for 2 h;

[0062] (5) Move the 24-well plate to a clean bench and rinse with PBS solution three times;

[0063] (6) Add DID cell membrane staining solution into the wells, stain at 37°C for 20 min, and rinse twice with PBS solution;

[0064] (7) Take out the slide from the well plate, add an appropriate amount of DAPI to cover the slide, and observe under a confocal microscope.

[0065] result: Figure 4 The results showed that compared with the normal group, the activated LX-2 cells uptake FERPep significantly more, proving that the self-assembled peptide nanomaterials increased the uptake of anti-fibrotic drugs by LX-2 cells. After adding PDGFRβ antibody, the uptake of FERPep by activated LX-2 cells decreased significantly, proving that PDGFRβ can competitively inhibit the specific binding of FERpep and PDGFRβ, indirectly indicating that PDGFRβ is the specific binding target of FERpep.

[0066] Embodiment 4:

[0067] In order to study the anti-fibrosis effect of self-assembled peptide nanomaterials in vitro, a cell immunofluorescence experiment was performed to investigate the inhibition of LX-2 cell activation by self-assembled peptide nanomaterials. The specific operation process is as follows:

[0068] The experiment was divided into 5 groups: normal group (Control), TGF-β1 group, the self-assembling polypeptide solution obtained after incubation in step (2) of Example 1 (Peptide group), PFD (pirfenidone) group, and PFD@ns group.

[0069] (1) LX-2 cells were seeded into a 24-well plate, with approximately 2 × 104 cells per well. The plate was placed in a cell culture incubator and cultured for 24 h.

[0070] (2) Except for the normal group, each group was induced with 10 ng / mL TGF-β1 for 48 h;

[0071] (3) 100 μM PFD solution was added to the PFD group, and 100 μM PFD-containing self-assembled peptide nanomaterials were added to the PFD@ns group, and incubated at 37°C for 24 h;

[0072] (4) Move the 24-well plate to a clean bench, rinse twice with PBS solution, and add 1 ml of tissue cell fixative to each well for 20 min;

[0073] (5) Remove the fixative and wash three times with PBS;

[0074] (6) 0.5% TritonX-100 solution was used to permeabilize the membrane for 15 min and then blocked with goat serum for 45 min;

[0075] (7) Add 150 μl of fibronectin primary antibody to each well and incubate at 4°C overnight; wash three times with PBS;

[0076] (8) Add 150 μl of secondary antibody and phalloidin solution to each well and incubate at room temperature in the dark for 2 h;

[0077] (9) Wash three times with PBS, mount the slides with DAPI, and take confocal photos;

[0078] result: Figure 5 The results showed that by immunofluorescence staining of LX-2 cells, TGF-β1 could induce LX-2 cell activation, and the expression of F-actin and Fibronectin increased significantly. Both PFD and PFD@ns groups could inhibit the activation of LX-2 cells, and the expression of Fibronectin and F-actin in the PFD@ns group was lower than that in the simple PFD group, indicating that the PFD@ns group had a stronger inhibitory effect on the activation of LX-2 cells.

[0079] Embodiment 5:

[0080] In order to study the anti-fibrosis effect of self-assembled peptide nanomaterials in vivo, CCl4 was used to induce liver fibrosis in mice, and HE staining, MSAAON staining, Sirius red staining, immunohistochemical staining, real-time fluorescence quantitative PCR experiments and Western Blot experiments were performed. The specific operation process is as follows:

[0081] 1. CCl4 induces liver fibrosis in mice:

[0082] (1) 25 8-week-old SPF male C57BL / 6 mice were divided into a normal group (Control), a blank control group (Untreated), the self-assembled peptide solution obtained in step (2) of Example 1 (Peptide group), a PFD group, and a PFD@ns group, with 5 mice in each group; except for the normal group, each group was intraperitoneally injected with a 25% CCl4 solution at a dose of 1 ml / kg, twice a week for 4 weeks; the blank control group was injected with an equal volume of normal saline;

[0083] (2) After CCl4 administration for 4 weeks, mice in the PFD group were given 10 mg / kg of PFD via the tail vein, and mice in the PFD@ns group were given self-assembled peptide nanomaterials containing 10 mg / kg of PFD via the tail vein, twice a week for 4 consecutive weeks;

[0084] (3) The peptide group and the normal group were treated with the same dose of peptide and saline via the tail vein twice a week for 4 weeks.

[0085] 2. Liver HE staining, Masson staining and Sirius red staining:

[0086] The liver tissues of mice were taken for paraffin sections, and the sections were stained with HE, Masson and Sirius red according to the standard procedures. The areas of liver fibrosis were counted after taking pictures with an optical microscope.

[0087] 3. Immunohistochemical staining of liver fibronectin and α-SMA:

[0088] The liver tissues of mice were taken for paraffin sections, and the liver fibronectin and α-SMA staining were performed according to the standard immunohistochemical staining method. The positive areas of liver fibronectin and α-SMA in each group were counted after taking pictures under an optical microscope.

[0089] 4. Real-time fluorescence quantitative PCR experiment:

[0090] Total RNA of the tissue was extracted using Trizol reagent. After total RNA was reverse transcribed into cDNA, RT-PCR analysis was performed using SYBR GreenMaster to quantify the expression of related genes α-SMA, type I collagen, type III collagen, and fibronectin.

[0091] 5. Western Blot experiment:

[0092] Fresh liver tissues were obtained from mice in each group, and total liver protein was extracted. After gel electrophoresis and electrotransfer, the bands were exposed using the Tanon imaging system, and the expression of α-SMA, type I collagen, type III collagen, and fibronectin in each group was quantitatively analyzed using Image J software.

[0093] Results: By Figure 6 The results of HE, Masson and Sirius red staining of mouse liver tissue showed that self-assembled polypeptide nanomaterials could reduce the area of ​​liver fibrosis in mice.

[0094] Depend on Figure 7 The immunohistochemical results showed that self-assembling peptide nanomaterials could significantly reduce the expression of α-SMA and Fibronectin in mouse liver.

[0095] Depend on Figure 8 The results of real-time fluorescence quantitative PCR experiments showed that compared with the mice in the fibrosis group, the mice in the simple peptide treatment group, and the mice in the simple PFD group, the expression of fibrosis-related factors was significantly downregulated after treatment with self-assembled peptide nanomaterials.

[0096] Depend on Fig. 9 Western Blot experiments demonstrated at the protein level that self-assembled polypeptide nanomaterials significantly reduced the expression levels of type I collagen, type III collagen, fibronectin and α-SMA.

[0097] From the above examples, it can be seen that a self-assembling polypeptide nanomaterial of the present invention can specifically bind to PDGFRβ protein, can responsively release anti-fibrosis drugs in FAP-α high expression areas, can improve the targeting of anti-fibrosis drugs in fibrotic tissues and prolong the retention time, can significantly reduce the mRNA expression and protein content of type I collagen, type III collagen, fibronectin, and α-SMA, and thus improve the therapeutic effect of anti-fibrosis drugs on fibrotic tissues. The self-assembling polypeptide nanomaterial of the present invention is used to treat mice with liver fibrosis, which can significantly reduce the degree of liver fibrosis in mice.

[0098] The self-assembling polypeptide nanomaterials encapsulating pirfenidone of the present invention were intravenously injected to treat mice with liver fibrosis, and the repair of fibrotic liver tissue was observed. After injection into fibrotic mice, firstly, because there is an SRNLID sequence in the self-assembling polypeptide sequence, which is a PDGFRβ binding site, the drug can be targeted and delivered to activated hepatic stellate cells that highly express PDGFRβ. Secondly, the self-assembling polypeptide nanomaterial is modified with a FAP-α response sequence, which can specifically release anti-fibrotic drugs in FAP-α high-expression areas, prolong the retention rate of anti-fibrotic drugs in fibrotic tissues, and significantly reduce the mRNA expression and protein expression of type I collagen, type III collagen, fibronectin, and α-SMA, thereby increasing the targeting of anti-fibrotic drugs and thus their anti-fibrotic effects. The self-assembling polypeptide nanomaterial has good biocompatibility, targeting and therapeutic effects, and can be used safely.

[0099] Any matters not described in the present invention are applicable to the prior art.

Claims

1. A self-assembling polypeptide, characterized in that The sequence of the self-assembling polypeptide is SRNLIDK[C 14 ]ATGPAK[C 14 ]DILNRS.

2. The self-assembling polypeptide according to claim 1, characterized in that The structural formula of the self-assembling polypeptide is:

3. The self-assembling polypeptide according to claim 1, characterized in that The self-assembling polypeptide comprises two SRNLID sequences, two C14 hydrocarbon tails and a FAP-α responsive sequence, wherein the SRNLID sequence is a PDGFRβ binding site; and the two SRNLID sequences are connected via the FAP-α responsive sequence.

4. A method for preparing a self-assembling polypeptide nanomaterial, characterized in that: The method comprises the following steps: Step 1, dissolving the self-assembling polypeptide according to any one of claims 1 to 3 in deionized water or PBS solution to obtain a self-assembling polypeptide solution; Step 2, incubating the self-assembling polypeptide solution obtained in step 1, during which the self-assembling polypeptide forms a fiber network structure, thereby obtaining a self-assembling polypeptide solution after incubation; Step 3, adding the hydrophobic anti-fibrosis drug solution to the incubated self-assembling polypeptide solution obtained in step 2, and subjecting the solution to ultrasonic treatment to break the fiber network structure and evenly wrap the hydrophobic anti-fibrosis drug molecules; and then incubating to form a self-assembling polypeptide nanomaterial with a nano-spherical skin-core structure in which the hydrophobic anti-fibrosis drug is wrapped by the self-assembling polypeptide.

5. The method for preparing the self-assembling polypeptide nanomaterial according to claim 4, characterized in that: In step 1, the dissolution process is: ultrasonication at a power of 150 to 200 W for 15 to 20 minutes to completely dissolve the polypeptide; In step 1, the concentration of the self-assembling polypeptide solution is 100 μg / mL to 1 mg / mL; In step 1, the concentration of the PBS solution is 0.1 mol / L.

6. The method for preparing the self-assembling polypeptide nanomaterial according to claim 4, characterized in that: In step 2, the incubation temperature is 30-37° C., and the incubation time is 24-48 h.

7. The method for preparing the self-assembling polypeptide nanomaterial according to claim 4, characterized in that: In step 3, the concentration of the hydrophobic anti-fibrosis drug solution is 100 μM to 1 mM; the volume ratio of the hydrophobic anti-fibrosis drug solution to the incubated self-assembling polypeptide solution is 1:100 to 500; In step 3, the hydrophobic anti-fibrotic drug is pirfenidone or nintedanib; In step 3, the ultrasonic process is: ultrasonication at a power of 150 to 200 W for 15 to 20 minutes; In step 3, the incubation temperature is 30-37° C., and the incubation time is 24-48 hours.

8. A self-assembling polypeptide nanomaterial prepared by the method for preparing a self-assembling polypeptide nanomaterial according to any one of claims 4 to 7.

9. Use of the self-assembling polypeptide nanomaterial according to claim 8 in the preparation of drugs for resisting organ or tissue fibrosis.

10. The use according to claim 9, characterized in that: The organ or tissue fibrosis is liver fibrosis, kidney fibrosis or myocardial fibrosis.

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