CN113307883A - Targeting polypeptide with anti-tumor and anti-angiogenesis effects - Google Patents
Targeting polypeptide with anti-tumor and anti-angiogenesis effects Download PDFInfo
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
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Abstract
The invention discloses a targeted polypeptide with anti-tumor and anti-angiogenesis functions, which is formed by combining a fluorescence unit, namely Bispyrene (BP), with an aggregation luminescence effect, an amino acid sequence capable of self-assembling into beta-sheet nano fibers and an amino acid sequence capable of targeted recognition of CD105 protein. The targeting polypeptide can target and identify the CD105 protein specifically expressed on the tumor stem cell membrane, self-assemble and destruct on the surface of the tumor stem cell to form stable water-insoluble nanofiber, adhere to the surface of the tumor stem cell and destroy the tumor stem cell, and further play a role in inhibiting the proliferation and metastasis of the tumor. The targeting polypeptide can also target tumor angiogenesis simultaneously, generate in-situ self-assembly aggregation on the cell surface, generate J-type aggregation emission fluorescence signals and form nano fibers, block gaps among endothelial cells, reduce the permeability of the tumor angiogenesis, inhibit angiogenesis, and finally play a role in inhibiting tumor proliferation and metastasis.
Description
Technical Field
The invention relates to the technical field of biology, in particular to a targeting polypeptide with anti-tumor and anti-angiogenesis functions.
Background
Renal cancer occupies the first ten malignant tumors in developed countries, accounting for 3.7% of all new cancer cases. Worldwide incidence rates continue to rise and prognosis is poor. Renal clear cell carcinoma is the most common type of carcinoma, accounting for approximately 80% of all cases, with high vascular density and high metastatic characteristics, with metastasis occurring in approximately 30% of patients at the time of diagnosis. Kidney cancer has become a prominent problem endangering human health.
The tumor stem cells are a cell subset with high malignancy degree in the tumor, have extremely strong metastatic capacity, can promote the tumor cells to generate distant metastasis in a paracrine mode, and are regarded as an initiating factor of tumor metastasis at present. Meanwhile, in the aspect of tumor angiogenesis, because endothelial cells are rapidly proliferated, the development of tumor blood vessels is not mature, and the gaps among the endothelial cells are relatively large, so that the tumor cells can easily enter blood circulation through the blood vessels to further play a role in tumor metastasis. The high permeability of the tumor's new blood vessels opens the door for tumor metastasis. Therefore, the simultaneous inhibition of renal cancer stem cells and tumor vessels has great significance for antagonizing the proliferation and metastasis of renal cancer.
CD105 is specifically and highly expressed on the endothelial cell membranes of renal cancer stem cells and new blood vessels, and is a common biomarker of tumor new blood vessels and renal cancer stem cells. Therefore, the invention constructs a polypeptide which can be targeted and identified and combined with CD105 and is named as TDS (transformed double-inhibited system), wherein the TDS has a targeting effect on renal cancer stem cells and tumor vascular endothelial cells, can form water-insoluble nanofibers through allosteric and living body self-assembly to be retained outside cell membranes for a long time, and has double effects of resisting tumors and inhibiting angiogenesis.
Disclosure of Invention
The invention aims to provide a targeting polypeptide with anti-tumor effect and anti-angiogenesis effect.
In order to achieve the purpose, the invention adopts the following technical means:
the invention relates to a targeting polypeptide (named TDS) capable of recognizing and combining CD105 protein to form water-insoluble nanofiber, which consists of the following three parts:
1) an amino acid sequence which can be self-assembled into beta-sheet nano fibers, wherein the amino acid sequence is shown as SEQ ID NO.1 (FFVLK); a FFVLK peptidyl sequence derived from amyloid beta, water-insoluble nanofibers that can self-assemble into β -sheet secondary structures due to hydrogen bond interactions;
2) an amino acid sequence for identifying the CD105 protein in a targeted way, wherein the amino acid sequence is shown as SEQ ID NO.2 (AHKHVHHVPVRL); a sequence that can target recognition of the CD105 protein, which acts as a target head in TDS, specifically binds to the target CD 105;
3) the fluorescent unit is Bispyrene (BP). Bispyrene is a typical AIE effect (aggregation induced emission) fluorescent molecule and can be used for observing TDS aggregation, self-assembly and allosteric processes.
Wherein, preferably, the polypeptide has a structure shown as the following formula:
the targeting polypeptide TDS can target and identify CD105 protein on a tumor stem cell membrane, self-assemble and destruct on the surface of a tumor stem cell to form stable water-insoluble nanofiber, adhere to the surface of the tumor stem cell and destroy the tumor stem cell, and further play a role in inhibiting the proliferation and metastasis of tumors. Experiments prove that the sternness of the renal cancer stem cells is inhibited by 68 +/-9.3% by the TDS of the targeting polypeptide. The metastasis and infiltration capacity of the renal cancer stem cells are respectively inhibited by 55.5 +/-1.8 percent and 62.7 +/-7.2 percent; on the other hand, the TDS can identify CD105 protein on the tumor neogenesis vascular endothelial cell membrane in a targeted way, and the nano fiber which is stable in water insolubility is formed by allosteric and living body self-assembly on the surface of the vascular endothelial cell and is adhered and encapsulated on the surface of the vascular endothelial cell, so that the density of the tumor blood vessel with strong permeability is enhanced, and the tumor cell is prevented from generating cancer metastasis by penetrating the endothelial cell. Meanwhile, in vivo and in vitro experiments also prove that the double-targeting polypeptide TDS has stronger anti-angiogenesis effect. Experimental data show that the targeting polypeptide TDS reduces the permeability of vascular endothelial cells by 33.0 +/-4.7 percent and inhibits angiogenesis by 38 +/-4.0 percent. Therefore, the targeting polypeptide TDS of the invention can play an anticancer role through two aspects of tumor resistance and tumor angiogenesis resistance.
Furthermore, the invention also provides application of the targeting polypeptide in preparing an anti-tumor medicament, wherein the tumor is a tumor with a CD105 membrane surface marker.
Wherein, preferably, the tumor comprises renal cancer, oral cancer and ovarian cancer. More preferably, the tumor is renal cancer.
Preferably, the targeting polypeptide has the effects of resisting tumor cell proliferation and metastasis.
Furthermore, the invention also provides the application of the targeting polypeptide in preparing a medicament for inhibiting tumor angiogenesis, and when the targeting polypeptide is used for inhibiting tumor angiogenesis, the targeted tumor can be a tumor with a CD105 membrane surface marker or a tumor without the CD105 membrane surface marker.
Preferably, the targeting polypeptide has the effects of reducing the permeability of tumor neovessels and inhibiting tumor angiogenesis.
Wherein, preferably, the tumor comprises renal cancer, oral cancer and ovarian cancer. More preferably, the tumor is renal cancer.
Compared with the prior art, the invention has the beneficial effects that:
the targeting polypeptide (named TDS) is formed by combining a fluorescent unit dipyrene (BP) with an aggregated luminescence effect, an amino acid sequence capable of self-assembling into beta-sheet nano fibers and an amino acid sequence capable of identifying CD105 protein in a targeted mode. TDS can be allosterically and self-assembled on the surface of tumor stem cells and tumor vascular endothelial cells to wrap the cells. The deformable target inhibition system (TDS) can be combined with tumor stem cells and tumor neovascularization in a targeted manner at the same time, and can be automatically assembled and gathered on the cell surface in situ to generate J-type gathering and emission fluorescence signals, form nanofibers to kill the tumor stem cells, block gaps among endothelial cells, reduce the permeability of the tumor blood vessels, inhibit angiogenesis and finally play a role in inhibiting tumor proliferation and metastasis.
In addition, the invention focuses on the practical problem of clinical transformation application, and human-derived peptide molecules are used as materials for design and construction, so that the TDS has strong biological safety and great clinical application potential.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed to be used in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without inventive exercise.
FIG. 1 shows the molecular structures of polypeptide TDS and polypeptide TDS-C of control group;
a) is a molecular structure pattern diagram of TDS, b) is a molecular structure pattern diagram of TDS-C;
FIG. 2 shows that polypeptide TDS can be destructurized and self-assembled in CD105 protein water solution to form hydrophobic nanofibers;
a) performing transmission electron microscope examination for TDS solution 0h and 12h after CD105 protein is added; b) the TDS-C solution is subjected to transmission electron microscopy at 0h and 12h after CD105 protein is added, and the scale is as follows: 50 nm;
FIG. 3 is a confocal microscope image and ThT fluorescence detection of polypeptide TDS and TDS-C incubated with renal Cancer Stem Cells (CSCs) and vascular endothelial cell membranes;
a) confocal microscopy images and ThT fluorescence detection after co-incubation of TDS and TDS-C with HUVEC cells, b) confocal microscopy images and ThT fluorescence detection after co-incubation of TDS and TDS-C with CSCs cells, scale: 20 μm;
FIG. 4 shows the killing effect and biological safety of polypeptide TDS on renal Cancer Stem Cells (CSCs) and vascular endothelial cells;
a) killing effect of TDS and TDS-C on CSCs cells, b) killing effect of TDS and TDS-C on HUVEC cells, C) toxicity of TDS and TDS-C on mouse major organs, scale: 100 μm;
FIG. 5 shows the ability of polypeptide TDS to inhibit the balling, migration and infiltration of renal cancer stem cells;
a) for influence and quantitative analysis of TDS and TDS-C on the balling capacity of the renal cancer stem cells, a ruler: 50 μm; b) for the influence and quantitative analysis of TDS and TDS-C on the migration capacity of the renal cancer stem cells, a ruler: 20 μm; c is the influence and quantitative analysis of TDS and TDS-C on the invasion capacity of the renal cancer stem cells, and the scale is as follows: 20 μm; compared with TDS-C, TDS is obtained,*P<0.05，**P<0.01；
FIG. 6 shows the effect of polypeptide TDS and TDS-C on vascular endothelial cell permeability and vascular mimicry formation;
a) influence of TDS and TDS-C on vascular endothelial cell permeability, b) influence of TDS and TDS-C on vascular mimicry formation and quantitative analysis, scale: 20 μm; compared with TDS-C, TDS is obtained,*P<0.05，**P<0.01；
FIG. 7 shows the in vivo distribution and metabolism of polypeptide TDS;
FIG. 8 shows the results of co-localization of polypeptide TDS and TDS-C with tumor blood vessels and inhibition of tumor angiogenesis;
a) is the co-localization of TDS and TDS-C with mouse tumor vessels, b) is the inhibition of TDS and TDS-C to mouse tumor vessels, scale: 100 μm;
FIG. 9 shows the inhibition of tumor growth by polypeptide TDS and TDS-C in vivo;
a) effect of TDS and TDS-C on mouse tumor proliferation, b) quantification of mouse tumor weight, C) quantification of mouse tumor volume, d) effect of TDS and TDS-C on mouse tumor metastasis.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in a stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification. The description and examples are intended to be illustrative only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including, but not limited to.
The invention will be further described with reference to the following examples, which are to be understood as being illustrative only and in no way limiting.
Example 1 preparation of targeting Polypeptides and molecular Structure
1. Preparation of targeting polypeptide TDS (BP-FFVLK-AHKHVHHVPVRL)
Can recognize and combine with CD105 protein to form water-insoluble nanofiber, the targeting polypeptide is composed of the following three parts:
1) an amino acid sequence which can be self-assembled into beta-sheet nano fibers, wherein the amino acid sequence is shown as SEQ ID NO.1 (FFVLK); a FFVLK peptidyl sequence derived from amyloid beta, water-insoluble nanofibers that can self-assemble into β -sheet secondary structures due to hydrogen bond interactions;
2) an amino acid sequence for identifying the CD105 protein in a targeted way, wherein the amino acid sequence is shown as SEQ ID NO.2 (AHKHVHHVPVRL); a sequence that can target recognition of the CD105 protein, which acts as a target head in TDS, specifically binds to the target CD 105;
3) the fluorescent unit is Bispyrene (BP). To observe the process of TDS aggregation, self-assembly, and allosterism, we selected bi-pyrene molecules as fluorescent signal molecules, bi-pyrene being a typical AIE effect (aggregation induced emission) fluorescent molecule.
2. Non-allosteric self-assembled control polypeptide TDS-C (BP-AHKHVHHVPVRL):
both TDS and TDS-C were prepared by solid phase synthesis.
The molecular structure pattern of polypeptide TDS and TDS-C is shown in FIG. 1.
Example 2 allosteric, self-assembly of Water-insoluble nanofibers following binding of a targeting polypeptide to CD105
CD105 reagent was added to the TDS and TDS-C polypeptide solutions and the TDS and TDS-C polypeptide solution samples were observed using transmission electron microscopy at 0 hours and 12 hours, respectively. The results are shown in FIG. 2. From this result, it can be seen that polypeptide TDS was allosteric and self-assembled in CD105 protein aqueous solution to form hydrophobic nanofibers, while TDS-C was not allosteric and self-assembled in CD105 protein aqueous solution to form hydrophobic nanofibers.
Example 3 cell assay
1. Method of administration
Dissolving TDS and TDS-C polypeptide in DMSO solvent to prepare polypeptide nano material solution with solution concentration of 4 mM. The experimental cells with good state and logarithmic growth are adopted and randomly divided into TDS, TDS-C and PBS (phosphate buffer solution) groups, the TDS, TDS-C and PBS solutions are slowly dripped into a culture medium at the concentration of 100 mu M, and the influence of the TDS, TDS-C and PBS solutions on the cell survival state is verified respectively.
2. The polypeptide generates fiber transition on the surfaces of vascular endothelial cells and renal cancer stem cells
HEK293 (human embryonic kidney cells), renal cancer stem cells of human tumors, HUVEC (human umbilical vein vascular endothelial cells) were cultured at 105/mL in culture dishes for 12 hours. TDS, TDS-C and PBS solutions were incubated with the cells at 37 ℃ for 12 hours and 24 hours, and then washed 3 times with PBS for laser scanning confocal microscopy measurements. The samples were examined under a 405nm laser using a 40 x immersion objective. Meanwhile, 104 cells were cultured in a 96-well plate for 12 hours, and then added with TDS, TDS-C or PBS solution and cultured for 24 hours. Three washes were performed with PBS. Thioflavin t (tht) was then added for 30 min and washed three times with PBS. The fluorescence intensity was measured under a fluorescent microplate reader.
The results are shown in FIG. 3. From this result, it can be seen that the polypeptide TDS can recognize aggregates on the surfaces of renal Cancer Stem Cells (CSCs) and vascular endothelial cell membranes.
Example 4 killing effect and biosafety of targeting polypeptides on vascular endothelial cells and renal cancer stem cells:
1. the cell administration method comprises the following steps:
the same as in example 3.
2. Renal cancer stem cell procurement of human tumors:
the human clear cell carcinoma tissue specimen is cut into 1mm3The cubic block is enzymolyzed into single cells. CD105+ cells were then isolated using anti-CD 105 antibody-coupled magnetic beads. CD105+ cells were cultured in CCRCC stem cell culture medium. Finally, the cells were incubated at 37 ℃ with 5% CO2And a cell culture box with saturated humidity.
3. The killing effect and the biological safety of the polypeptide on vascular endothelial cells and renal cancer stem cells are as follows:
HEK293 (human embryonic kidney cells), human tumor-derived renal cancer stem cells, and HUVECs (human umbilical vein vascular endothelial cells) which are in good state and grow logarithmically are added into a 96-well plate at a rate of 8 × 103 cells per well and in a total volume of 100 μ l, and placed in a 37-degree incubator, after 24 hours, the cells are randomly divided into TDS, TDS-C, and PBS groups, TDS-C, and PBS solutions are added at concentrations of 10 μ M, 20 μ M, 50 μ M, 100 μ M, and 200 μ M, respectively, and placed in a 37-degree incubator, after 24 hours, the culture medium is discarded, the prepared CCK-8 solution is added, and the incubator is placed in a 37-degree incubator for 1-4 hours, and the absorbance is measured. Three groups of mice were given TDS and TDS-C, PBS once every 2 days, intravenously 7 times, and were taken out, organ specimens were examined by H & E staining.
The results are shown in FIG. 4. From the results, the TDS has killing effect on the human tumor-derived renal cancer stem cells and HUVEC, and H & E staining examination results of organ specimens show that no significant difference exists among three groups of mice, which indicates that the TDS and the TDS-C have biological safety.
Example 5 inhibition of Balling, infiltration, migration of renal cancer Stem cells by targeting Polypeptides
1. Cell administration method
The same as in example 3.
2. Human tumor renal cancer stem cell harvesting
The same as in example 4.
3. Inhibition effect of targeted polypeptide on renal cancer stem cell balling, infiltration and migration
The human tumor renal cancer stem cells which are in good state and grow logarithmically are placed in a DMEM/F12 culture medium containing 20ng/mL EGF, 20ng/mLbFGF and B27 to be cultured for 7-10 days to obtain tumor stem cell spheres, the cell spheres are collected by a gravity method, and enzymolysis is carried out for 10-15min to obtain single tumor stem cells. Then, the cells are paved in a low-viscosity six-well plate at a density of 5000 cells per well for stem cell culture, TDS-C and PBS solution are added every two days, and the number of cell balls larger than 50nm is counted after 7 days. In migration and invasion experiments, the upper chamber of a Transwell (8 μm pore size, polycarbonate filter, 6.5 mm diameter; corning) was coated or uncoated with matrigel (BD bioscience, Franklin lake, N.J., USA) to verify invasion and migration of cells, respectively. The cells were placed in culture medium containing TDS, TDS-C or PBS solution, respectively. 1mL of DMEM/F12 medium containing 50ng/mL of Epidermal Growth Factor (EGF) was placed in the lower chamber. After incubation at 37 ℃ for 48h, the lower layer of invaded cells was counted by staining.
The results are shown in fig. 5, and it can be seen from the results that polypeptide TDS has a function of significantly inhibiting proliferation, migration, and infiltration of renal cancer stem cells.
Example 6 inhibition of vascular endothelial permeability and angiogenesis by targeting polypeptides.
The cell administration method was as in example 3. Adopting human umbilical vein endothelial cells HUVEC which are in good state and grow logarithmically, adding 50 mu L of matrigel into a Transwell upper chamber paved in advance according to the cell concentration of each hole 104, placing the Transwell upper chamber into an incubator at 37 ℃ for incubation, after the cells are fused into a single layer, washing the Transwell upper chamber and the Transwell lower chamber by PBS, sucking out the PBS, respectively adding culture solution containing TDS-C, TDS and PBS solution into the upper chamber, incubating the incubator for 24h, sucking out the upper chamber liquid, washing the upper chamber by PBS, adding 200 mu L of FITC-Dextran (fluorescein isothiocyanate-Dextran) into the upper chamber, adding 200 mu L of PBS solution into the lower chamber, incubating the incubator for 3h, taking 100 mu L of each of the upper chamber and the lower chamber, placing the upper chamber and the lower chamber into a 96-well plate, and detecting the permeability of the endothelial cells by a fluorescence microplate reader. Meanwhile, human umbilical vein endothelial cells HUVEC which are in good state and grow logarithmically are adopted, the cell concentration of each hole 104 is added into a 96-hole plate paved with 50 mu L matrigel in advance, the cells are randomly divided into TDS, TDS-C and PBS groups, TDS-C and PBS solutions are respectively added at the concentration of 100 mu M, the TDS, TDS-C and PBS solutions are placed in a 37-degree incubator, and the cells are photographed and observed after 24 hours and are subjected to statistical analysis by using image J.
The results are shown in FIG. 6. From this result, it can be seen that the polypeptide TDS can decrease vascular endothelial cell permeability and inhibit the proliferation thereof.
Example 7 targeting polypeptide distribution, metabolism in mice.
Balb/c nude mice are adopted in the experiment, and tumor tissue cells of a patient with metastatic renal cancer are inoculated on the right shoulder of the mice. When the tumor volume reaches 50mm3Mice were injected with 100. mu.L of TDS (400. mu.M/mouse), TDS-C (400. mu.M/mouse), PBS (400. mu.M/mouse), respectively, by intravenous infusion. 1,12,24,4 after injectionFluorescence imaging of mice was monitored for 8 hours using a multispectral fluorescent in vivo small animal imaging system.
The results are shown in FIG. 7. From the results, the TDS polypeptide is mainly distributed around the tumor tissues, which shows that the TDS polypeptide has good targeting property and can be metabolized by the body.
Example 8, co-localization of the targeting polypeptide with mouse tumor vessels and inhibition of tumor angiogenesis.
Balb/c nude mice are adopted in the experiment, and tumor tissue cells of a patient with metastatic renal cancer are inoculated on the right shoulder of the mice. When the tumor volume reaches 50mm3Mice were injected with 100. mu.L of TDS (400. mu.M/mouse), TDS-C (400. mu.M/mouse), PBS (400. mu.M/mouse), respectively, by intravenous infusion. And taking the tumor for immunofluorescence and immune group detection 12 hours after injection, and verifying the co-localization of the targeting polypeptide and the tumor blood vessel of the mouse and the inhibition effect on the tumor blood vessel.
The results are shown in FIG. 8. From this result, it can be seen that the polypeptide TDS can co-localize with tumor blood vessels and inhibit tumor angiogenesis.
Example 9 targeting Polypeptides in mice to inhibit tumor growth and Lung metastasis
Balb/c nude mice are adopted in the experiment, and tumor tissue cells of a patient with metastatic renal cancer are inoculated on the right shoulder of the mice. When the tumor volume reaches 50mm3Mice were injected with 100. mu.L of TDS (400. mu.M/mouse), TDS-C (400. mu.M/mouse), PBS (400. mu.M/mouse) by intravenous infusion once every 2 days, and administered intravenously 7 times. During the experiment, tumor volume and body weight were measured every 2 days. Taking out the specimen, and performing immunohistochemistry and lung metastasis determination.
The results are shown in FIG. 9. From this result, it can be seen that the polypeptide TDS is capable of inhibiting tumor proliferation as well as angiogenesis and metastasis in vivo.
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.
Sequence listing
<110> Harbin university of medicine
<120> a targeting polypeptide with anti-tumor and anti-angiogenesis effects
<130> KLPI190478
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 5
<212> PRT
<213> artificial sequence
<400> 1
Phe Phe Val Leu Lys
1 5
<210> 2
<211> 12
<212> PRT
<213> artificial sequence
<400> 2
Ala His Lys His Val His His Val Pro Val Arg Leu
1 5 10
Claims (10)
1. A targeting polypeptide, wherein the polypeptide is targeted to recognize and combine with CD105 protein to form water-insoluble nanofiber, and the targeting polypeptide is composed of the following three parts:
1) an amino acid sequence which can be self-assembled into beta-sheet nano-fiber is shown as SEQ ID NO. 1;
2) the amino acid sequence of the targeting recognition CD105 protein is shown as SEQ ID NO. 2;
3) the fluorescent unit is Bispyrene (BP).
2. The targeting polypeptide of claim 1, wherein said polypeptide has the structure of formula:
3. the use of the targeting polypeptide of claim 1 or 2 in the preparation of an anti-tumor medicament, wherein said tumor is a tumor having a CD105 membrane surface marker.
4. The use of claim 3, wherein the neoplasm comprises renal cancer, oral cancer, ovarian cancer.
5. The use according to claim 4, wherein the neoplasm is renal cancer.
6. The use of any one of claims 3 to 5, wherein the targeting polypeptide has an anti-tumour cell proliferation, metastasis effect.
7. The use of the targeting polypeptide of claim 1 or 2 in the preparation of a medicament for inhibiting tumor angiogenesis.
8. The use of claim 7, wherein the targeting polypeptide has the effects of decreasing the permeability of tumor neovasculature and inhibiting tumor angiogenesis.
9. The use according to claim 7 or 8, wherein the neoplasm comprises renal cancer, oral cancer, ovarian cancer.
10. The use according to claim 9, wherein the neoplasm is renal cancer.
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