Anti-protein adhesion polypeptide nanomaterial, preparation method and application thereof

Abstract

This invention provides an anti-protein adhesion peptide nanomaterial, its preparation method, and its application. The anti-protein adhesion peptide nanomaterial comprises a nanomaterial substrate and an anti-protein adhesion peptide modified on the nanomaterial substrate. The anti-protein adhesion peptide has any one or at least two combinations of the amino acid sequences selected from SEQ ID NO: 1-8. This invention creatively discovers that peptide nanomaterials prepared from the anti-protein adhesion peptide having any one or at least two combinations of the amino acid sequences selected from SEQ ID NO: 1-8 as a raw material exhibit excellent anti-protein adhesion activity. Furthermore, due to the enhanced anti-adhesion activity, the peptide nanomaterial has a longer blood circulation half-life and also possesses higher biocompatibility. The anti-protein adhesion peptide nanomaterial of this invention provides a new option for biological anti-protein adhesion materials.

Description

Technical Field

[0001] This invention belongs to the field of nanomaterials, specifically relating to an anti-protein adhesion polypeptide nanomaterial, its preparation method, and its application. Background Technology

[0002] A tumor is a new growth formed by the proliferation of local tissue cells under the influence of various tumorigenic factors. Tumor nanomaterials (NMs) are often considered promising drug delivery carriers in multifunctional therapeutics. However, the clinical application of these nanomaterials is hindered by low bioavailability, poor serum stability, and limited blood half-life. When tumor nanomaterials are intravenously injected into the body, they inevitably adsorb proteins, forming protein coronas. Protein coronas can unexpectedly alter the surface properties of NMs, leading to a reduction in the blood circulation half-life and changes in the biodistribution of tumor nanomaterials.

[0003] CN105131087A discloses a Vibrio mimicryl OmpU adhesin protein-binding peptide with adhesion antagonistic activity, a polypeptide composition, and their applications. SEQ ID NO:1-3 are all 12 peptides, and the Vibrio mimicryl OmpU adhesin protein-binding peptide is composed of the amino acid sequence SEQ ID NO:1. The polypeptide composition consists of three polypeptides: SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, with a mass ratio of 1:1:1 for the polypeptides shown in SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3. The OmpU adhesin protein-binding peptide and its polypeptide composition with adhesion antagonistic activity in this invention can not only specifically bind to OmpU adhesin protein but also effectively inhibit Vibrio mimicryl from adhering to and colonizing the intestinal mucosa surface through this adhesin, thereby reducing the virulence of Vibrio mimicryl. Adhesion antagonists made from OmpU adhesive protein-binding peptides and their polypeptide compositions, which have adhesion antagonistic activity, can effectively prevent and treat fish ascites caused by Vibrio mimicus.

[0004] CN112795030A discloses a drug-loaded anti-adhesion contact lens hydrogel material and its preparation method. This invention relates to the field of polymer hydrogel technology, and particularly to a drug-loaded anti-adhesion contact lens hydrogel material and its preparation method. The drug-loaded anti-adhesion contact lens hydrogel material is formed by copolymerizing hydroxyethyl methacrylate, acrylic acid, zwitterionic monomers, and hydrophobic monomers, and then loading the drug onto the copolymer. The drug-loaded anti-adhesion contact lens hydrogel material of this invention has good light transmittance, a certain drug loading capacity and can achieve sustained drug release, stable dehydration-replenishment performance, high water content and stable water retention rate, and excellent anti-protein and anti-bacterial adhesion properties. The preparation method is simple, efficient, and environmentally friendly, requiring no special equipment, and is easy to industrialize.

[0005] Currently, researchers have developed various methods to prepare nanomaterials that can resist protein crown formation. Polyethylene glycol (PEG), zwitterionic choline (PC), and peptides have been used to prevent protein adhesion to nanomaterials, but all have certain shortcomings. Therefore, exploring novel anti-protein adhesion materials is of great significance. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide an anti-protein adhesion polypeptide nanomaterial, its preparation method, and its application.

[0007] To achieve this objective, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides an anti-protein adhesion peptide nanomaterial, the anti-protein adhesion peptide nanomaterial comprising:

[0009] The nano-substrate material and the anti-protein adhesion peptide modified on the nano-substrate material, wherein the anti-protein adhesion peptide has any one or a combination of at least two of the amino acid sequences shown in SEQ ID NO: 1-8.

[0010] The combination of at least two includes the combination of SEQ ID NO:1 and SEQ ID NO:2, the combination of SEQ ID NO:1 and SEQ ID NO:3, the combination of SEQ ID NO:3 and SEQ ID NO:5, etc. Any other combination can be selected, and will not be described in detail here.

[0011] The amino acid sequences shown in SEQ ID NO: 1-8 are as follows:

[0012] (1)THDYGAV (SEQ ID NO: 1);

[0013] (2) HNAGYDV (SEQ ID NO: 2);

[0014] (3) VGAYIAP (SEQ ID NO: 3);

[0015] (4) WTIQAQP (SEQ ID NO: 4);

[0016] (5) PGFVQQP (SEQ ID NO: 5);

[0017] (6) VWVQAQP (SEQ ID NO: 6);

[0018] (7) KWQQAQP (SEQ ID NO: 7);

[0019] (8)GPDEWYY(SEQ ID NO: 8).

[0020] This invention creatively discovers that peptide nanomaterials prepared from the anti-protein adhesion peptides having any one or at least two combinations of the amino acid sequences shown in SEQ ID NO: 1-8 possess excellent anti-protein adhesion properties. Furthermore, due to the enhanced anti-adhesion effect, the peptide nanomaterials exhibit a longer blood circulation half-life and higher biocompatibility. The anti-protein adhesion peptide nanomaterials of this invention provide a new option for biological anti-protein adhesion materials.

[0021] Preferably, the nanomaterial substrate includes any one or a combination of at least two of metal nanoparticles, magnetic nanoparticles, or inorganic nanoparticles; the combination of at least two includes: a combination of metal nanoparticles and magnetic nanoparticles, a combination of magnetic nanoparticles and inorganic nanoparticles, or a combination of inorganic nanoparticles and metal nanoparticles, etc. Other combinations are also possible and will not be described in detail here.

[0022] Preferably, the metal nanoparticles include gold nanorods.

[0023] The nanomaterial substrate described in this invention can be a nanomaterial known to those skilled in the art, such as gold nanorods.

[0024] Preferably, the anti-protein adhesion peptide nanomaterial is further modified with PEG.

[0025] Preferably, the molecular weight of the PEG is 1000-8000.

[0026] The specific values ​​in the range of 1000-8000 can be selected from 1000, 2000, 3000, 4000, 5000, 6000, 7000 or 8000, etc. Other specific point values ​​within the above range can also be selected, which will not be elaborated here.

[0027] When the anti-protein adhesion peptide nanomaterial of the present invention is modified with PEG, the composite anti-protein adhesion peptide nanomaterial has a stronger anti-adhesion effect and a longer blood circulation half-life. In particular, when the molecular weight of PEG is selected between 1000-8000, the effects in these two aspects are even better. Moreover, when the anti-protein adhesion peptide nanomaterial containing PEG is applied to mice, it will not cause organ damage to the mice, and has high biosafety.

[0028] Preferably, the anti-protein adhesion peptide nanomaterial contains 0.1-0.5 parts of anti-protein adhesion peptide per unit mass of nanomaterial substrate.

[0029] The specific values ​​in the range of 0.1-0.5 can be 0.1, 0.2, 0.3, 0.4, or 0.5. Other specific values ​​within the range of the above values ​​can also be selected, and will not be elaborated on here.

[0030] When the grafting rate of the anti-protein adhesion peptide nanomaterial of the present invention is 0.1-0.5 parts per unit mass of nano-substrate material containing the anti-protein adhesion peptide, the anti-protein adhesion nanomaterial has a stronger anti-adhesion effect.

[0031] In a second aspect, the present invention provides a method for preparing anti-protein adhesion polypeptide nanomaterials as described in the first aspect, the preparation method comprising the following steps:

[0032] (1) Pretreatment of nanomaterials to obtain spare nano-substrate materials;

[0033] The anti-protein adhesion peptide was pretreated to prepare a ready-to-use anti-protein adhesion peptide.

[0034] (2) Mix the prepared nano-substrate material and the prepared anti-protein adhesion peptide in step (1), centrifuge, add water and incubate to obtain the anti-protein adhesion peptide nanomaterial.

[0035] The preparation method of the anti-protein adhesion peptide nanomaterials involved in this invention is simple to operate and suitable for industrial scale-up.

[0036] Preferably, the method for pretreating nanomaterials in step (1) includes:

[0037] A seed-mediated method was used to prepare a standby nano-substrate material with a surface containing a bilayer of hexadecyltrimethylammonium bromide.

[0038] Preferably, the method for pretreating the anti-protein adhesion peptide in step (1) includes:

[0039] The C-terminus of the anti-protein adhesion peptide was modified with a cysteine ​​SH functional group to prepare a ready-to-use anti-protein adhesion peptide.

[0040] The nanomaterials described in this invention can be pretreated to obtain a spare nano-substrate material with a surface containing a bilayer of hexadecyltrimethylammonium bromide. After the C-terminus of the anti-protein adhesion peptide is modified with a cysteine ​​SH functional group, the spare nanomaterials can be bound to the spare anti-protein adhesion peptide through a ligand exchange reaction to obtain the anti-protein adhesion peptide nanomaterials.

[0041] Preferably, stirring is performed during the mixing process in step (2).

[0042] Preferably, the stirring temperature is 20-38℃ and the stirring time is 8-16h.

[0043] The specific values ​​in the 20-38℃ range can be 20℃, 22℃, 24℃, 26℃, 28℃, 30℃, 32℃, 34℃, 36℃, or 38℃.

[0044] The specific values ​​in the 8-16h range can be 8h, 10h, 12h, 14h, or 16h, etc.

[0045] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0046] Preferably, the centrifugation speed in step (2) is 10,000-14,000 rpm, and the centrifugation time is 10-30 min.

[0047] The specific value in the 10000-14000rpm range can be selected from 10000rpm, 11000rpm, 12000rpm, 13000rpm, or 14000rpm, etc.

[0048] The specific values ​​in the 10-30 min range can be selected as 10 min, 14 min, 18 min, 22 min, 26 min, or 30 min, etc.

[0049] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0050] Preferably, the incubation time in step (2) is 8-24 hours and the incubation temperature is 2-8℃.

[0051] The specific values ​​in the 8-24h range can be selected as 8h, 10h, 12h, 14h, 16h, 18h, 20h, 22h, or 24h, etc.

[0052] The specific values ​​in the 2-8℃ range can be 2℃, 4℃, 6℃ or 8℃.

[0053] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0054] Thirdly, the present invention provides a pharmaceutical composition, wherein the raw materials for preparing the pharmaceutical composition include the anti-protein adhesion polypeptide nanomaterials as described in the first aspect.

[0055] Fourthly, the present invention provides the use of the anti-protein adhesion polypeptide nanomaterial as described in the first aspect, the preparation method as described in the second aspect, or the pharmaceutical composition as described in the third aspect in the preparation of an anti-protein adhesion device.

[0056] Fifthly, the present invention provides the use of the anti-protein adhesion polypeptide nanomaterials as described in the first aspect, the preparation method as described in the second aspect, or the pharmaceutical composition as described in the third aspect in the preparation of anti-protein adhesion tumor drugs.

[0057] Compared with the prior art, the present invention has the following beneficial effects:

[0058] 1. This invention creatively discovers that peptide nanomaterials prepared from the anti-protein adhesion peptide having any one or at least two combinations of the amino acid sequences shown in SEQ ID NO: 1-8 possess excellent anti-protein adhesion properties. Furthermore, due to the enhanced anti-adhesion effect, the peptide nanomaterials exhibit a longer blood circulation half-life and higher biocompatibility. The anti-protein adhesion peptide nanomaterials of this invention provide a new option for biological anti-protein adhesion materials.

[0059] 2. The method for preparing anti-protein adhesion peptide nanomaterials involved in this invention is simple to operate and suitable for industrial scale-up. Attached Figure Description

[0060] Figure 1 The images shown are TEM images from Example 2, where a is a TEM image of the nanomaterial GNRs; b is a TEM image of the nanomaterial GNRs after co-incubation with the protein; c is a TEM image of the nanomaterial GNRs-PEG2000 after co-incubation with the protein; d is a TEM image of the nanomaterial GNRs-SEQ ID NO: 1 after co-incubation with the protein; and e is a TEM image of the nanomaterial GNRs-PEG2000-SEQ ID NO: 1 after co-incubation with the protein. Detailed Implementation

[0061] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0062] The processes, conditions, reagents, and experimental methods used in implementing this invention, except as specifically mentioned below, are all common knowledge and general knowledge in the field, and this invention does not have any particular limitations. Experimental methods in the embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer.

[0063] Unless otherwise stated, all technical terms and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. However, in the event of any conflict, the specification containing the definitions shall prevail.

[0064] The PEG2000 used in the following examples is a product purchased from Solarbio, with product number P8190.

[0065] Example 1

[0066] Synthetic anti-protein adhesion peptide nanomaterials

[0067] 1. Preparation of anti-protein adhesion peptides (AAPs): The anti-protein adhesion peptides were manually synthesized according to the amino acid sequences in Table 1 using the standard Fmoc chemical solid-phase peptide synthesis method.

[0068] Table 1

[0069] name amino acid sequence SEQ ID NO: 1 THDYGAV SEQ ID NO: 2 HNAGYDV SEQ ID NO: 3 VGAYIAP SEQ ID NO: 4 WTIQAQP SEQ ID NO: 5 PGFVQQP SEQ ID NO: 6 VWVQAQP SEQ ID NO: 7 KWQQAQP SEQ ID NO: 8 GPDEWYY

[0070] 2. Preparation of anti-protein adhesion peptide nanomaterials:

[0071] (1) Preparation of gold nanorods GNR modified with hexadecyltrimethylammonium bromide (CTAB) using seed-mediated method: 7.5 mL of 0.1 M CTAB was mixed with 100 μL of 24 mM tetrachloroauric acid (HAuCl4), and deionized water was added to dilute to 9.4 mL;

[0072] Subsequently, under strong magnetic stirring, 0.6 mL of pre-cooled NaBH4 (0.01 M) was added on ice. The solution color immediately changed from bright yellow to brown, indicating Au seed formation. A growth medium was prepared by mixing CTAB (100 mL, 0.1 M), HAuCl4 (2.04 mL, 4 mM), AgNO3 (1.05 mL, 10 mM), and ascorbic acid AA (552 μL, 0.1 M). 120 μL of Au seed solution was added to this medium. After 12 h, AA (55.2 μL, 0.1 M) was added to the mixture, and AA (55.2 μL, 0.1 M) was added again after 40 min. The reaction mixture was then allowed to react for 24 h. After the reaction was complete, the mixture was centrifuged at 12000 rpm for 5 min. The precipitate was washed twice with water and resuspended in 50 mL of deionized water to obtain gold nanorods (GNRs) modified with hexadecyltrimethylammonium bromide (CTAB).

[0073] (2) Centrifuge 1 mL of 5 nM gold nanorods (GNRs) modified with hexadecyltrimethylammonium bromide (CTAB) at 14000 rpm for 15 min, wash 3 times with PBS buffer to remove residual CTAB, and dilute to 1 mL with PBS buffer.

[0074] (3) Obtaining anti-protein adhesion peptide nanomaterials through ligand exchange reaction: 1 mg of each of the eight C-terminal cysteine ​​SH-functionalized anti-protein adhesion peptides AAP were added to the solution in (2), stirred at 25°C for 12 h, centrifuged at 14000 rpm for 15 min to remove excess AAP, washed with PBS buffer, and repeated 3 times to obtain anti-protein adhesion peptide nanomaterials GNRs-APPs (of which GNRs-AAPs include GNRs-SEQ ID NO: 1-8);

[0075] GNRs-PEG2000 was prepared by replacing the C-terminal functionalized AAPs with SH-functionalized PEG2000.

[0076] Eight C-terminal cysteine ​​SH-functionalized anti-protein adhesion peptides (AAPs) were mixed with GNRs-PEG2000, with the molar concentration of AAP being one-tenth that of GNRs-PEG2000. The pH was adjusted to 9 with triethylamine, and the mixture was incubated at 4°C for 12 hours to prepare GNRs-PEG2000-AAPs (GNRs-PEG2000-AAPs include GNRs-PEG2000-SEQ ID NO: 1-8).

[0077] Cy5-NHS-labeled anti-protein adhesion peptide nanomaterials were prepared for subsequent experiments. The concentrations of Cy5-NHS and Cy5-PEG2000-SH were one-tenth of the molar concentrations of AAPs and PEG2000-SH, respectively. After adjusting the pH to 9 with triethylamine, the nanomaterials were incubated at 4°C for 12 hours to obtain Cy5-NHS-labeled anti-protein adhesion peptide nanomaterials.

[0078] Example 2

[0079] Anti-protein adhesion test

[0080] The anti-protein adhesion effect of the anti-protein adhesion peptide nanomaterials was evaluated using a BCA protein concentration assay kit and transmission electron microscopy (TEM).

[0081] (1) Place GNRs-PEG2000-AAPs, GNRs-AAPs, GNRs-PEG2000 and GNRs in 1mM BSA solution, incubate at 37℃ for 4h, centrifuge at 4000rpm for 3min, take the precipitate and dilute to 200μL with PBS buffer to obtain the sample to be tested.

[0082] (2) Prepare a protein standard curve and test samples according to the instructions of the BCA protein concentration assay kit. Then, use an ELISA reader to detect the absorbance of the test samples at 562 nm. Calculate the protein concentration and protein concentration difference rate based on the standard curve. Protein concentration difference rate (%) = (protein concentration of each group / protein concentration corresponding to the GNRs group) × 100%.

[0083] (3) The TEM images of the test samples were characterized using a Tecnai G2 20STWIN at an accelerating voltage of 200 kV. The test samples prepared in step (1) were diluted with deionized water to 5 nM, and 10 μL of each sample was dropped onto a copper grid. After standing for 5 min, the liquid was wiped dry with filter paper. Subsequently, the copper grid was stained with uranium acetate solution for 40 s, washed with 10 μL of deionized water, blotted dry, and dried at 25 °C. After complete drying, the samples were placed in the Tecnai G2 20STWIN instrument for detection. Figure 1 TEM images of the GNRs group, GNRs-PEG2000 group, GNRs-SEQ ID NO: 1 group, and GNRs-PEG2000-SEQ ID NO: 1 group are given.

[0084] Table 2

[0085]

[0086]

[0087] As shown in Table 2, the protein concentration difference rate of the 8 groups corresponding to GNRs-AAPs is less than 100%, indicating that the anti-protein adhesion peptide nanomaterials of the present invention have a stronger anti-protein adhesion effect compared with GNRs alone. The protein concentration difference rate of the 8 groups contained in GNRs-AAPs-PEG2000 is even lower than that of the 8 groups contained in GNRs-AAPs, and also lower than that of the GNRs-PEG2000 group, indicating that the anti-protein adhesion peptides and PEG2000 can synergistically enhance the anti-protein adhesion effect of the peptide nanomaterials.

[0088] Depend on Figure 1 As shown in the transmission electron microscopy images, after GNRs are incubated with proteins, their surfaces are surrounded by a lighter-colored substance, which is the protein crown formed by the adhesion protein. After GNRs-PEG2000 is incubated with proteins, the surface of the nanomaterial is rough, while the surfaces of GNRs-AAPs and GNRs-AAPs-PEG2000 nanomaterials are smooth and no protein crown is observed. This indicates that the anti-protein adhesion peptides described in this invention can achieve a good anti-protein adhesion effect.

[0089] Example 3

[0090] Half-life of anti-protein adhesion nanomaterials

[0091] 150 μL of 150 μM solutions of GNRs-AAPs-PEG2000, GNRs-AAPs, GNRs-PEG2000, and GNRs were intravenously injected into 6-week-old female BALB / c mice (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., including normal control mice injected with 150 μL of physiological saline). Five mice were in each group. At 5 min, 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h post-injection, 20 μL of venous blood was collected from the tail and added to 50 mL of PBS buffer containing 15 mg / mL LEDTA. The mixture was centrifuged at 3000 rpm for 10 min at 4°C to remove blood cells. The supernatant plasma was collected and its absorbance was measured at 650 nm using an ELISA reader. Based on the absorbance value and the standard curve of GNRs concentration-absorbance value, the concentration of GNRs in the sample is calculated, and then the half-life difference rate of the sample in blood circulation is obtained. Half-life difference rate = (half-life of each group / half-life of the corresponding GNRs group) × 100%.

[0092] Table 3

[0093] name Half-life difference rate (%) GNRs 100 GNRs-PEG2000 124 GNRs-SEQ ID NO: 1 177 GNRs-SEQ ID NO: 2 153 GNRs-SEQ ID NO: 3 142 GNRs-SEQ ID NO: 4 126 GNRs-SEQ ID NO: 5 183 GNRs-SEQ ID NO: 6 133 GNRs-SEQ ID NO: 7 131 GNRs-SEQ ID NO: 8 144 GNRs-PEG2000-SEQ ID NO: 1 185 GNRs-PEG2000-SEQ ID NO: 2 168 GNRs-PEG2000-SEQ ID NO: 3 167 GNRs-PEG2000-SEQ ID NO: 4 165 GNRs-PEG2000-SEQ ID NO: 5 199 GNRs-PEG2000-SEQ ID NO: 6 181 GNRs-PEG2000-SEQ ID NO: 7 142 GNRs-PEG2000-SEQ ID NO: 8 193

[0094] As shown in Table 3, the half-life difference rate of the 8 groups corresponding to GNRs-AAPs is higher than that of the GNRs group, indicating that the anti-protein adhesion peptide nanomaterials of the present invention have a longer half-life in blood circulation compared with GNRs alone. In addition, the half-life difference rate of the 8 groups contained in GNRs-AAPs-PEG2000 is higher than that of the 8 groups contained in GNRs-AAPs, and also higher than that of the GNRs-PEG2000 group, indicating that the anti-protein adhesion peptides and PEG2000 can synergistically enhance the anti-protein adhesion effect of the peptide nanomaterials, thereby enhancing the blood circulation half-life of the composite material.

[0095] Example 4

[0096] Biosafety testing

[0097] (1) 150 μL of 150 μM GNRs-AAPs-PEG2000, GNRs-AAPs, GNRs-PEG2000 and GNRs solutions were intravenously injected into 6-week-old BALB / c female mice, with 5 mice in each group. In addition, 5 normal control mice were injected with 150 μL of physiological saline.

[0098] (2) Seventy-two hours after intravenous injection, blood was collected from the tail vein of mice. The mice were then euthanized, and their heart, liver, spleen, lungs, kidneys, pancreas, brain, and muscle tissues were dissected. These tissues were fixed in 4% paraformaldehyde-PBS buffer for 12 hours, then embedded in paraffin and sectioned. The sections were stained using hematoxylin-eosin staining. Blood was allowed to stand at 25°C for 10 minutes, and the supernatant was used to detect biochemical indicators using a Hitachi 7100 fully automated biochemical analyzer: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, blood urea nitrogen, and serum creatinine.

[0099] Table 4

[0100]

[0101]

[0102] Tissue sections prepared from the heart, liver, spleen, lungs, kidneys, pancreas, brain, and muscle tissues of mice showed that the structures of each organ in each group of mice were intact, the cells were of normal size and morphology, and were neatly arranged, with no cell degeneration, necrosis, or inflammatory cell infiltration observed.

[0103] As shown in Table 4, the values ​​of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and serum creatinine in mice in the GNRs-AAPs-PEG2000 group, GNRs-AAPs group, GNRs-PEG2000 group, and GNRs group were similar to those in the normal control group and were within the normal range. This indicates that the anti-protein adhesion polypeptide nanomaterials described in this invention have high biological safety and will not cause damage to the function and morphology of the heart, liver, kidneys, spleen, lungs, pancreas, brain, and muscles.

[0104] The applicant declares that the present invention is illustrated by the above embodiments, but the present invention is not limited to the above process steps, that is, it does not mean that the present invention must rely on the above process steps to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions of the raw materials used in the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0105] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0106] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A polypeptide nanomaterial with anti-protein adhesion properties, characterized in that, The anti-protein adhesion peptide nanomaterials include: The nano-substrate material and the anti-protein adhesion peptide modified on the nano-substrate material, wherein the amino acid sequence of the anti-protein adhesion peptide is SEQ ID NO: 6 or 8; The anti-protein adhesion polypeptide nanomaterial is also modified with PEG. The molecular weight of the PEG is 2000; The anti-protein adhesion peptide nanomaterial has an anti-protein adhesion peptide grafting rate of 0.1-0.5 parts per unit mass of nano-substrate material. The nanomaterial substrate is gold nanorods.

2. A pharmaceutical composition, characterized in that, The raw materials for preparing the pharmaceutical composition include the anti-protein adhesion polypeptide nanomaterials as described in claim 1.

3. The use of an anti-protein adhesion polypeptide nanomaterial as described in claim 1 or a pharmaceutical composition as described in claim 2 in the preparation of an anti-protein adhesion device.

4. The use of an anti-protein adhesion polypeptide nanomaterial as described in claim 1 or a pharmaceutical composition as described in claim 2 in the preparation of an anti-protein adhesion tumor drug.

Images