Targeted Tie2 amphiphilic molecule, targeted Tie2 polypeptide self-assembled nano-drug as well as preparation method and application of targeted Tie2 amphiphilic molecule and targeted Tie2 polypeptide self-assembled nano-drug

Abstract

The invention discloses an amphiphilic polypeptide drug carrier targeting Tie2 and a polypeptide nano-drug targeting Tie2 protein, and belongs to the field of biological medicine. The drug carrier is a spherical nano particle formed by self-assembly of an amphiphilic molecule DSPE-PEG-PH1 (DP1) targeted by Tie2, and the amphiphilic molecule DSPE-PEG-PH1 (DP1) targeted by Tie2 is a spherical nano particle. The polypeptide self-assembled nano-drug comprises a hydrophobic anti-tumor drug and a drug carrier coating the drug, meanwhile, the invention also discloses a preparation method and application thereof, amphiphilic polypeptide and a hydrophobic drug are dissolved in an organic phase, are uniformly mixed under an ultrasonic condition and then are dispersed into a water phase to obtain the Tie2-targeted polypeptide self-assembled nano-drug (DEP1), so that the in-vivo circulation time of the drug can be prolonged, efficient targeting of a breast tumor part can be realized, and the application range of the drug is widened. Growth of mouse breast tumors is remarkably inhibited, anti-tumor immunity is promoted, and an effective novel method is provided for treating the breast cancer.

Description

Technical Field

[0001] The present invention belongs to the technical field of polypeptide nanomaterials, and particularly relates to an amphiphilic molecule targeting Tie2, a polypeptide self-assembly nanomedicine targeting Tie2, and a preparation method and application thereof. Background Art

[0002] So far, the commonly used cancer treatment methods in clinical practice mainly include: surgery, radiotherapy and chemotherapy, among which chemotherapy is the most important comprehensive method in the process of cancer treatment. However, most chemical drugs used to treat cancer have disadvantages such as poor solubility and short half-life. Moreover, after directly entering the body, chemotherapy drugs are mainly distributed in normal tissues, and only a small part (2-5%) can act on tumor tissues, showing the characteristics of poor targeting.

[0003] Current studies have confirmed that tumor growth depends not only on the proliferation of tumor cells, but also on the environment in which they are located, namely the tumor microenvironment. The main members of the tiny blood vessels that constitute the main source of oxygen and nutrients for solid tumors are endothelial cells, which play an important role in promoting the metastasis of tumor cells and regulating the migration of immune cells. In addition, macrophages, as the main component of immune infiltration in cancer, are an indispensable element in the tumor microenvironment. In solid tumors represented by breast cancer, angiogenesis involving endothelial cells and inflammatory states mediated by macrophages can affect the development of solid tumors. A number of preclinical studies have confirmed that EP4 antagonists may indirectly affect the occurrence, development and metastasis of tumors by affecting endothelial cell angiogenesis and macrophage phenotypic transformation.

[0004] In recent years, self-assembling peptide nanomaterials have been widely studied and applied in the fields of nanotechnology and medical nanomaterials. Studies have found that self-assembly can improve the targeting, aggregation and stability of drug molecules, thereby significantly improving the efficacy of drugs. Peptide self-assembly refers to a type of molecular aggregate or supramolecular structure with a clear structure, stable structure and certain physical and chemical properties formed by the spontaneous combination of amino acid residues through non-covalent bond interactions under appropriate conditions. Non-covalent bond interactions include hydrogen bonds, electrostatic interactions, van der Waals forces and π-π stacking effects.

[0005] As a highly conserved receptor tyrosine kinase, Tie2 is highly expressed in vascular endothelial cells, tumor-associated macrophages and tumor cells, and is widely involved in tumor angiogenesis. It has always been the main research focus of tumor microenvironment therapy. Summary of the invention

[0006] The purpose of the present invention is to provide a peptide amphiphilic drug carrier targeting Tie2, a peptide self-assembly nanodrug targeting Tie2, and a preparation method and application thereof. The peptide amphiphilic drug carrier targeting Tie2 provided by the present invention can effectively prolong the half-life of the drug, and can specifically target the tumor site, so that the drug can be efficiently delivered to the tumor site, which not only improves the efficacy of the anti-tumor drug, but also reduces its toxic side effects.

[0007] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical scheme:

[0008] In a first aspect, the present invention provides a polypeptide amphiphilic drug carrier targeting Tie2, wherein the drug carrier is a spherical nanoparticle formed by self-assembly of amphiphilic molecules, wherein the amphiphilic molecules are DSPE-PEG-PH1, which is a targeting peptide PH1 of Tie2 connected by DSPE-PEG through an amide bond.

[0009] As a further preferred embodiment of the present invention, the chemical structure of the DSPE-PEG-PH1 is as shown in Formula 1:

[0010]

[0011] As a further preferred embodiment of the present invention, the sequence of the targeting peptide PH1 is shown as SEQ ID NO.1.

[0012] In a second aspect, the present invention also discloses a peptide self-assembled nanomedicine targeting Tie2 prepared using the amphiphilic drug carrier, wherein the peptide self-assembled nanomedicine comprises a hydrophobic anti-tumor drug and a drug carrier coated on the outside of the hydrophobic anti-tumor drug, and the hydrophobic anti-tumor drug is encapsulated in the hydrophobic interior of the amphiphilic drug carrier.

[0013] As a further preferred embodiment of the present invention, the hydrophobic anti-tumor drug is Palupiprant (E7046).

[0014] In a third aspect, the present invention further discloses a method for preparing the Tie2-targeting polypeptide self-assembly nanomedicine, comprising the following steps:

[0015] (1) adding the Tie2-targeting amphiphilic polypeptide DSPE-PEG-PH1 and the hydrophobic anti-tumor drug E7046 to the organic phase in sequence and mixing them to obtain a drug mixture; the mixing mass ratio of the amphiphilic polypeptide molecule to the hydrophobic anti-tumor drug is 1:(0.5-0.6);

[0016] (2) The organic phase of step (1) is dispersed in the aqueous phase, ultrasonicated at 60-100W for 10-15min, and allowed to stand at room temperature for 30-40min to obtain the nanomedicine of the present invention.

[0017] As a further preferred embodiment of the present invention, in step (2), the aqueous phase is deionized water or a phosphate buffer with a pH of 7.4.

[0018] As a further preferred embodiment of the present invention, in step (1), the organic phase is dimethyl sulfoxide.

[0019] As a further preferred embodiment of the present invention, the amphiphilic polypeptide molecule DSPE-PEG-PH1 in step (1) is prepared by the following steps:

[0020] (a) 5 mg DSPE-PEG2000-mal 1.22 μmol and 1.6 mg PH1 were mixed and the solvent was removed by rotary evaporation, and then 5 mL water was added to resuspend the mixture to obtain a resuspended solution;

[0021] (b) The resuspended solution of step (a) was transferred to a dialysis bag with a molecular weight cut-off of 3500 Da, and the white powder obtained by dialysis and drying was DSPE-PEG-PH1. In this step, the dialysis time was 3 days, and the purpose of dialysis was to remove the unreacted PH1.

[0022] In a fourth aspect, the present invention further discloses the use of the polypeptide amphiphilic drug carrier in the preparation of tumor immunotherapy drugs or tumor targeting imaging agents.

[0023] As further preferred embodiment of the present invention, the tumor is breast cancer.

[0024] The overall inventive concept of the present invention is as follows:

[0025] Current studies have confirmed that tumor growth depends not only on the proliferation of tumor cells, but also on the tumor microenvironment in which they are located. The main members of the tiny blood vessels that constitute the main source of oxygen and nutrients for solid tumors are endothelial cells, which play an important role in promoting the metastasis of tumor cells and regulating the migration of immune cells. In addition, macrophages, as the main component of immune infiltration in cancer, are an indispensable element in the tumor microenvironment. In solid tumors represented by breast cancer, endothelial cell-involved angiogenesis and macrophage-mediated inflammatory states can affect the development of solid tumors. Several preclinical studies have confirmed that EP4 antagonists may indirectly affect the occurrence, development and metastasis of tumors by affecting endothelial cell angiogenesis and macrophage phenotypic transformation.

[0026] The inventors found that Tie2 is highly expressed in vascular endothelial cells and macrophages in the tumor microenvironment, participates in tumor angiogenesis, and affects the tumor immune microenvironment. Therefore, the inventors believe that the tumor microenvironment can be improved by delivering anti-tumor drugs by targeting Tie2. Based on this, the present invention provides an amphiphilic molecule targeting Tie2 and a polypeptide self-assembled nanomedicine targeting Tie2. The amphiphilic molecule and the hydrophobic anti-tumor drug self-assemble to form nanoparticles under ultrasonic conditions, in order to utilize the specific targeting of the amphiphilic molecule to deliver the anti-tumor drug, effectively improve the half-life, stability and bioavailability of the nanomedicine in the body, and develop a new dosage form of anti-tumor drug for the current biomedicine field.

[0027] In the present invention, the particle size of the Tie2-targeting polypeptide self-assembled nanomedicine is 160-200 nm, which is relatively small, and is conducive to the endocytosis of endothelial cells and macrophages in the tumor microenvironment, and has in vivo stability and is not easily degraded.

[0028] Compared with the prior art, the present invention has the following technical effects:

[0029] One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0030] The present invention is simple and easy to operate. The prepared amphiphilic molecule DSPE-PEG-PH1 targeting Tie2 can be assembled under ultrasonic conditions to form a highly ordered nanostructure, which not only retains the ability of PH1 to target Tie2-positive cells, but also has in vivo stability, effectively improving the half-life, stability and bioavailability of the polypeptide in vivo. In addition, the nanostructure can be used as a drug carrier to extend the half-life of the drug, and can efficiently deliver the drug to the tumor site, so that the anti-tumor drug is specifically released in the tumor microenvironment, effectively improving the targeting and half-life of the anti-tumor drug in vivo. Finally, the present invention preferably uses the above polypeptide nanostructure to deliver the hydrophobic anti-tumor drug EP4 antagonist Palupiprant (E7046), which indirectly achieves the anti-tumor effect by inhibiting endothelial cell angiogenesis, enhancing anti-tumor immunity, etc., and highlights the synergistic effect of targeting Tie2-specific cells to antagonize EP4 activity in the treatment of breast cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0032] Figure 1The biological transmission electron microscope image of the prepared peptide nanomedicine under physiological conditions;

[0033] Figure 2 Verify the tumor targeting of fluorescent targeting compounds DP4@Cy5 and DP1@Cy5 to cells and vectors;

[0034] Figure 3 The results of different treatments verifying the effects of different treatments on the in vitro migration and tube-forming ability of endothelial cells and the phenotype of macrophages;

[0035] Figure 4 The tumor growth curves of breast cancer EO771 tumor-bearing mice during the treatment cycle and the statistical graph of tumor weight after treatment were shown;

[0036] Figure 5 The expression of angiogenesis and CD8 in tumor tissues of mice in each group after treatment + Statistical chart of changes in T cells;

[0037] Figure 6 It shows the weight changes of mice in each group during the treatment period, serum biochemical indexes and HE staining images of isolated organs after the treatment period;

[0038] Figure 7 It is the structural formula of the amphiphilic molecule in the prepared nanomedicine. DETAILED DESCRIPTION

[0039] The present invention will be described in detail below in conjunction with specific implementations and examples, and the advantages and various effects of the present invention will be more clearly presented. It should be understood by those skilled in the art that these specific implementations and examples are used to illustrate the present invention, rather than to limit the present invention.

[0040] The amphiphilic polypeptide molecule DSPE-PEG-PH1 described in the present invention is prepared by the following steps:

[0041] (a) 5 mg DSPE-PEG2000-mal 1.22 μmol and 1.6 mg PH1 were mixed and the solvent was removed by rotary evaporation, and then 5 mL water was added to resuspend the mixture to obtain a resuspended solution;

[0042] (b) The resuspended solution of step (a) was transferred to a dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed for 3 days. The liquid in the dialysis bag was freeze-dried to obtain a white powder, which was DSPE-PEG-PH1.

[0043] Example 1

[0044] In this example, the polypeptide nanomedicine of the present invention is prepared by the following method:

[0045] (1) The amphiphilic molecule DP1 (structural formula: Figure 7 ), hydrophobic anti-tumor drug E7046 is sequentially added to the organic phase dimethyl sulfoxide to obtain a drug mixture; the mixing mass ratio of the amphiphilic molecule to the hydrophobic anti-tumor drug is 1:0.5 (in other embodiments, the mixing mass ratio can also be 1:0.6);

[0046] (2) The drug mixture of step (1) is dispersed in a phosphate buffer solution of pH 7.4, ultrasonicated at 80W for 12min, and allowed to stand at room temperature for 35min, thereby obtaining the nanomedicine of the present invention, which is named DEP1. In other embodiments, the organic phase of step (1) is dispersed in the aqueous phase, ultrasonicated at 60-100W for 10-15min, and allowed to stand at room temperature for 30-40min, and the effect of the invention can be achieved.

[0047] The morphology and particle size of the obtained nanodrug (DEP1) were characterized by transmission electron microscopy and laser particle size analyzer. The peptide PH4 (SHHSTSQPATNK) screened by phage was used as a control peptide, and a peptide nanodrug without targeting Tie2 function (named DEP4) was designed by the same method as a control. The results are as follows Figure 1 shown.

[0048] from Figure 1 It can be seen that the prepared nanomedicines DEP1 and DEP4 are spherical and the particle size is relatively uniform.

[0049] Example 2

[0050] The purpose of this example is to verify the targeting affinity of the nanomedicine prepared in Example 1 to Tie2 protein in vitro and in vivo.

[0051] First, the amphiphilic peptides (DP1, DP4) and DSPE-PEG-Cy5 (excitation light 650nm, emission light 670nm) were taken in a mass ratio of 9:1, each dissolved in 10μL dimethyl sulfoxide, and added to PBS for 30min of ultrasonication after complete dissolution. The nanomedicines DP4@Cy5 and DP1@Cy5 were obtained by standing at room temperature.

[0052] Secondly, vascular endothelial cells (HUVECs) and macrophages (RAW246.7) that highly express Tie2 were cultured at 2.5×10 4 The cells were seeded at a density of 100 cells / well in a 6-well plate. After the cells formed a confluent monolayer, the targeting probe DP1@Cy5, the control probe DP4@Cy5 and the solvent control (PBS) were added to the cells. One hour after the addition of the drugs, the drug uptake by the cells was detected by flow cytometry. The results are shown in Figure 2 A and Figure 2As shown in B, the signal intensity of the targeted probe DP1@Cy5-treated group in endothelial cells and macrophages was significantly higher than that of the control probe DP4@Cy5-treated group.

[0053] In addition, a certain amount of tumor cells EO771 were subcutaneously injected into the right hind limb of C57 / BL6 female mice to establish a subcutaneous tumor model of breast cancer. 3 The mice were randomly divided into three groups: PBS group, DP4@Cy5 group, and DP1@Cy5 group. The targeting probe DP1@Cy5 and the control probe DP4@Cy5 were injected into the subcutaneous breast cancer tumor-bearing mice through the tail vein at a dose of 10 mg / kg. The in vivo and in vitro fluorescence intensity was observed on a small animal in vivo imaging device 12h and 24h after the injection of the fluorescent probe, and photos were taken.

[0054] The results are as follows Figure 2 C and Figure 2 As shown in D, both the targeting probe DP1@Cy5 and the control probe DP4@Cy5 are highly enriched in the tumor site, and the fluorescence intensity of the targeting probe DP1@Cy5 is significantly higher than that of the control probe DP4@Cy5 group. This shows that the targeted nanodrug DEP1 prepared in Example 1 can target the vascular endothelial cells and macrophages that highly express Tie2 in the tumor microenvironment, effectively improving the half-life, stability and bioavailability of the nanodrug in vivo.

[0055] Example 3

[0056] The purpose of this example is to verify the regulatory effect of the nanomedicine prepared in Example 1 on endothelial cells (HUVECs) and macrophages (RAW246.7) in vitro.

[0057] First, HUVECs were cultured at 2.5x10 4 The cells were inoculated at a density of cells / well in a 6-well plate. After the cells formed a confluent monolayer, a 1 mL sterile pipette tip was used to perpendicularly scratch two parallel wounds. The wounds were washed with PBS three times, and then treated with PBS, PH1, E7046, DEP4, and DEP1 in sequence. Pictures were taken under a bright field microscope, recorded as 0 h and the position of the picture was marked. The cells were placed in a cell culture incubator and cultured for 12 h. After 12 h, pictures were taken at the same position and compared with the scratch width at 0 h. The scratch width reflects the effect of different treatments on the migration ability of HUVEC cells. ImageJ software was used to calculate the changes in scratch width before and after different treatments. The results are shown in the figure. Figure 3As shown in A, after treatment with the anti-tumor drug E7046, the control peptide DEP4, and the targeting peptide DEP1, the scratch width was significantly greater than that of the PBS group, and there was a significant statistical difference compared with the PBS group. This shows that E7046, DEP4 and DEP1 can significantly inhibit the migration of HUVEC cells. Similarly, Matrigel basement membrane matrix gel (50 μL / well) was applied to a 96-well culture plate and polymerized at 37°C for 30 minutes. HUVECs were inoculated on the Matrigel surface, and the nanodrug prepared in Example 1 was added and incubated for 4 hours. The tubule structure was imaged using a bright field microscope. The results are shown in Figure 2. Figure 3 As shown in B, the DEP4 and DEP1 treatment groups can significantly inhibit the formation of tubules. This indicates that the nanomedicine prepared in Example 1 can inhibit angiogenesis by inhibiting the migration and tubule formation of vascular endothelial cells.

[0058] Secondly, RAW246.7 is converted to 2.5x10 4 The cells were seeded in a 6-well plate at a density of 100 cells / well. When the cell density reached 80%, PBS, PH1, E7046, DEP4, and DEP1 were added for treatment. After 12 hours, M1 (CD45 + F4 / 80 + MHC-II + ) and M2 (CD45 + F4 / 80 + CD206 + ) were labeled with macrophage-specific antibodies and analyzed by flow cytometry. Figure 3 C and Figure 3 As shown in D: DEP1 can significantly increase the proportion of macrophages tumor immunity M1 type and reduce the proportion of tumor immunity inhibition M2 type. This shows that the nanomedicine prepared in Example 1 can affect tumor immunity by regulating macrophage phenotypic differentiation.

[0059] Example 4

[0060] The purpose of this example is to verify the in vivo anti-tumor effect of the nanomedicine prepared in Example 1.

[0061] First, a certain amount of tumor cells EO771 were injected subcutaneously into the right hind limb of C57 / BL6 female mice to establish a subcutaneous tumor model of breast cancer. When the tumor volume reached 100-200mm 3 The mice were randomly divided into 5 groups: PBS, PH1, E7046, DEP4, and DEP1. The drugs were administered every other day for a total of 6 times. During the entire treatment experiment, the tumor volume of the mice was monitored every 2 days. The tumor volume calculation formula was: tumor volume (mm 3 )=0.5×width 2 (mm2 )×length (mm), such as Figure 4 As shown in A, the DEP1 group had a significant inhibitory effect on tumor growth compared with the other groups. After the treatment cycle, the mice were euthanized, the mice were dissected, and the tumors were removed and weighed. Figure 4 As shown in B, consistent with the in vitro measurement results, the tumor weight of mice treated with DEP1 was the smallest (average tumor weight: 1.48 g), and the tumor in the PBS group grew rapidly (average tumor weight: 2.8 g).

[0062] Example 5

[0063] The purpose of this example is to verify the potential anti-tumor mechanism of the nanomedicine prepared in Example 1.

[0064] Similar to Example 4, after the treatment cycle, tumor tissue was taken for embedding and sectioning. Figure 5 As shown in A, vascular endothelial cells (CD31 + ) ratio was significantly lower than that of the other groups, indicating that the targeted nanomedicine DEP1 can significantly inhibit angiogenesis in tumor tissues. In addition, flow cytometry was performed on the tumor tissues of the above groups to determine the CD8 + T cells (CD3 + CD8+) changes, such as Figure 5 As shown in B, CD8 + T cells were significantly higher than those in the other groups, indicating that the targeted nanomedicine DEP1 can promote the proliferation of CD8 + T cell infiltration, thereby inhibiting tumor growth.

[0065] Example 6

[0066] The purpose of this experimental example is to verify the in vivo safety evaluation of the nanomedicine prepared in Example 1.

[0067] As in Example 3, the weight changes of mice were monitored every 2 days during the treatment period. Figure 6 As shown in A, the results show that the nanomedicine has no significant effect on the body weight of mice. After the treatment cycle, the serum of mice was taken to measure serum biochemical indicators, such as Figure 6 As shown in B, the results show that the nanomedicine has no significant effect on mouse liver function (ALT, AST), kidney function (CREA, BUN), etc. In addition, tumor tissues and mouse organs were removed, and HE staining was performed on sections of important organs such as the heart (Heart, H), liver (Liver, Li), spleen (Heart, H), lung (Lung, L), and kidney (Kidney, K). Figure 6As shown, the results show that the nano drug has no effect on the heart, liver, spleen, lung, kidney, etc. of mice. The above results show that the nano drug prepared by the present invention has good safety in vivo.

[0068] The above is only a preferred embodiment of the present invention, and does not limit the present invention in other forms. Any person skilled in the art can use the above disclosed technical content to change or modify it into an equivalent embodiment with equivalent changes. However, any simple modification, equivalent change and modification made to the above embodiment according to the technical essence of the present invention without departing from the technical solution of the present invention still belongs to the protection scope of the technical solution of the present invention.

Claims

1. A polypeptide amphiphilic drug carrier targeting Tie2, characterized in that: The drug carrier is a spherical nanoparticle formed by self-assembly of amphiphilic molecules, and the amphiphilic molecules are DSPE-PEG-PH1, which is a targeting peptide PH1 to which DSPE-PEG is connected to Tie2 via an amide bond.

2. The amphiphilic polypeptide drug carrier targeting Tie2 according to claim 1, characterized in that: The chemical structure of the DSPE-PEG-PH1 is shown in Formula 1:

3. The Tie2-targeting polypeptide amphiphilic drug carrier according to claim 1, characterized in that: The sequence of the targeting peptide PH1 is shown in SEQ ID NO.

1.

4. A polypeptide self-assembly nanomedicine targeting Tie2 prepared by using the amphiphilic drug carrier according to claim 1 or 2, characterized in that: The polypeptide self-assembled nano drug comprises a hydrophobic anti-tumor drug and a drug carrier coated on the outside of the hydrophobic anti-tumor drug, and the hydrophobic anti-tumor drug is contained in the hydrophobic interior of the amphiphilic drug carrier.

5. The polypeptide self-assembly nanomedicine targeting Tie2 according to claim 3, characterized in that: The hydrophobic anti-tumor drug is Palupiprant (E7046).

6. The method for preparing the peptide self-assembly nanomedicine targeting Tie2 according to claim 3, characterized in that: The following steps are involved: (1) dissolving the amphiphilic polypeptide molecule DSPE-PEG-PH1 and the hydrophobic drug E7046 in an organic phase to obtain a drug mixture; the mixing mass ratio of the amphiphilic polypeptide molecule to the hydrophobic anti-tumor drug is 1:(0.5-0.6); (2) The drug mixture of step (1) is dispersed in the aqueous phase, ultrasonicated at 60-100W for 10-15min, and allowed to stand at room temperature for 30-40min to obtain the nano drug of the present invention.

7. The method for preparing the peptide self-assembly nanomedicine targeting Tie2 according to claim 5, characterized in that: In step (2), the aqueous phase is deionized water or a phosphate buffer solution with a pH of 7.

4.

8. The method for preparing the peptide self-assembly nanomedicine targeting Tie2 according to claim 5, characterized in that: In step (1), the organic phase is dimethyl sulfoxide.

9. The method for preparing the peptide self-assembly nanomedicine targeting Tie2 according to claim 5, characterized in that: In step (1), the amphiphilic polypeptide molecule DSPE-PEG-PH1 is prepared by the following steps: (a) 5 mg DSPE-PEG2000-mal 1.22 μmol and 1.6 mg PH1 were mixed and the solvent was removed by rotary evaporation, and then 5 mL water was added to resuspend the mixture to obtain a resuspended solution; (b) The resuspended solution was transferred to a dialysis bag with a molecular weight cutoff of 3500 Da, and the white powder obtained after dialysis and drying was DSPE-PEG-PH1.

10. Use of the polypeptide amphiphilic drug carrier according to claim 1 or 2 in the preparation of tumor immunotherapy drugs or tumor targeting imaging agents.

11. The use according to claim 8, characterized in that: Application of nanomedicine in the treatment of breast cancer.

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