CN107903307A - A kind of high-affinity EDB FN targeting proteins peptides and its application - Google Patents
A kind of high-affinity EDB FN targeting proteins peptides and its application Download PDFInfo
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- CN107903307A CN107903307A CN201710966956.0A CN201710966956A CN107903307A CN 107903307 A CN107903307 A CN 107903307A CN 201710966956 A CN201710966956 A CN 201710966956A CN 107903307 A CN107903307 A CN 107903307A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
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Abstract
The present invention relates to a kind of target short peptide A16 of fibronectin EDB hypospecificities, its amino acid sequence is ATYRLFQGVEVV.The EDB FN albumen of target short peptide A16 energy specific recognition tumor cells expression of the present invention, it is high to the affinity of EDB FN, the functional molecular with diagnosis or therapeutic activity can be carried to tumour cell, performance diagnoses or therapeutic effect.
Description
Technical field
The invention belongs to molecular biology and immunological technique field, and in particular to phage display peptide library technology and restructuring
Expression technology, more particularly to a kind of screening, identification, preparation and the application of high-affinity EDB-FN targeting proteins peptides.
Background technology
It is well known that malignant tumour is in a unique microenvironment, promote growth, the diverging of tumour cell
With transfer.High expression that would generally be abnormal in tumor extracellular matrix and the relevant albumen of tumour, wherein, fibronectin
(fibronectin) it is one of most important albumen in tumor extracellular matrix, the process of the generation, growth in tumour and transfer
In play a crucial role.In addition, found in long-term scientific research, an important hypotype extradomain- of fibronectin
B fibronectin (EDB-FN) become the tumour that medical field is generally acknowledged in the growth course height correlation with tumour in patient body
Occur and Epithelial and stromal differentiation important biomolecule marker.EDB albumen has very high expression in the most of tumours of human body, including
Breast cancer, lung cancer, liver cancer, colorectal cancer, prostate cancer, head and neck cancer and lymthoma, glioma and melanoma etc..
So the marker that EDB is a great development prospect is checked, diagnoses and treated for the accurate of tumour.
Small peptide has the physiology course of human body (hormone, neurotransmitter, growth factor, ion-channel ligands and anti-infective)
Important effect.At present, the natural polypeptides being confirmed is more than 7000.Usual small peptide can be used as cell surface receptor high
The signaling molecule of compatibility, can trigger cell internal effect.Since pharmacological action of the small peptide with temptation and cost are low
Feature, a kind of new small peptide targeted drug and tumour are precisely imaged the popular research direction for becoming field of medicaments.Should
The dodecapeptide that being obtained with small peptide screening technique with EDB albumen there is height to combine power has broad application prospects.
Display technique of bacteriophage is a kind of polypeptide display technique of fast high-flux, using display technique of bacteriophage,
The screening high affine targeting antibodies and functional polypeptide of energy fast high-flux.Currently with the method for random synthesis, can incite somebody to action
Up to 109 different polypeptide sequences are shown to phage surface, it is established that the peptide library of one big storage capacity, by optimal screening side
Method is possible to filter out the short peptide molecules of different demands.Short peptide molecules are smaller to be easy to wear film, but usually affinity is relatively low, particularly
The frequent phenomenon of missing the target when carrying other molecules.The target polypeptide of high-affinity can be obtained, except being subject to screening technique
Condition and parameter influence beyond, be heavily dependent on enchancement factor.In addition, short peptide molecules structure is relatively easy, as
Specificity is not generally also high when targeting label, and specificity deficiency also have impact on application of the small peptide as targeted molecular.
The content of the invention
To solve the above problems, the present invention obtains one by repeatedly carrying out repeated screening to phage random peptide library
There is specific target tropism, the dodecapeptide of high affinity to EDB-FN albumen, and demonstrate it and carry diagnostic flag specific target
To the function of the tumour cell of expression EDB-FN.
On the one hand, a kind of EDB-FN targeting proteins peptide A16, its amino acid sequence such as SEQ ID NO:Shown in 1.
EDB-FN targeting proteins peptide of the present invention can also be in SEQ ID NO:Further pass through amino acid on the basis of 1
Substitution, missing, addition derive, preferably in SEQ ID NO:The substitution of 1,2,3 amino acid is carried out on the basis of 1, lacks, add
Add, such as conservation of amino acids substitution is carried out on 1 site.
Second aspect, the present invention provide a kind of conjugate, include targeting moiety and Functional portions, it is characterised in that described
Targeting moiety is the targeting peptides A16.
Conjugate of the present invention, it is characterised in that the targeting peptides containing one or more copies in the conjugate
A16。
Conjugate of the present invention, it is characterised in that the Functional portions include being selected from by diagnostic flag, chemotherapeutic
The group of thing, bioactive molecule composition.
Conjugate of the present invention, it is characterised in that can be directly connected to or between each component of the conjugate by connecing
Head connection, such as between the Functional portions and the targeting moiety, between the multiple Functional portions, the multiple target
To being directly connected between part or connected by connector.
The preferably peptide bond that is directly connected to is directly connected to；Connector such as (GGS) n of connector connection, (GGGS) n,
(GGGGS) n, wherein n are 2-6.
The third aspect, the present invention provide a kind of nucleic acid, it is encoded：
(1) EDB-FN targeting proteins peptide A16 of the present invention；Or
(2) conjugate of the present invention.
Nucleic acid of the present invention both include be adapted to procaryotic cell expression, by protokaryon codon optimization nucleic acid (such as
Use e. coli codon etc.), also include be adapted to eukaryotic cell expression, by eucaryon codon optimization nucleic acid (such as
Use yeast codons, mammalian cell codon etc.).
Nucleic acid of the present invention can be ribonucleic acid (RNA), or DNA (DNA).
Fourth aspect, the present invention provide a kind of nucleic acid construct, and it includes code nucleic acid of the present invention.
In nucleic acid construct of the present invention, the code nucleic acid is operably connected to promoter downstream, and contains
Protokaryon and/or eucaryon replication initiation sequence.
Nucleic acid construct of the present invention can be expression cassette, operator, plasmid, clay, virus/phage vector etc..
5th aspect, the present invention provide a kind of host cell, it includes encoding gene of the present invention or include the present invention
The nucleic acid construct；
Host of the present invention can express EDB-FN targeting proteins peptide A16 or of the present invention of the present invention and include
The conjugate of EDB-FN targeting proteins peptides A16.
Host of the present invention, can be the common host of genetic engineering field, including prokaryotic hosts, eucaryon host.Institute
State prokaryotic hosts and include but not limited to Escherichia coli, the eucaryon host includes but not limited to yeast (Pichia pastoris, wine brewing ferment
It is female), insect cell, mammalian cell, plant cell etc..
6th aspect, the present invention provide a kind of production EDB-FN targeting proteins peptide A16 or described and include EDB-FN eggs
The method of the conjugate of white targeting peptides A16, including：
(1) recombinant host cell of the present invention is prepared；
(2) host cell of incubation step (1) under the suitable conditions, makes its propagation；
(3) state of host cell and quantity reach when meeting production requirement, in suitable recombinant production EDB-FN protein targets
Host cell is cultivated under conditions of to peptide A16 or its conjugate；
(4) fraction comprising EDB-FN targeting proteins peptide A16 or conjugate is isolated and purified from host cell product.
7th aspect, the present invention provide the EDB-FN targeting proteins peptide A16 conjugates or the purposes of its conjugate, it is used
In the kit for preparing detection or diagnosis EDB-FN albumen.
The purposes of EDB-FN targeting proteins peptide A16 conjugates of the present invention or its conjugate, can be also used for preparation and examines
The medicine of relevant tumour is expressed in disconnected or treatment with EDB-FN abnormal proteins；It is described relevant swollen with the expression of EDB-FN abnormal proteins
Knurl include breast cancer, lung cancer, liver cancer, colorectal cancer, prostate cancer, head and neck cancer and lymthoma, glioma and
Melanoma.
Compared with prior art, technical scheme has the following advantages：
(1) molecule is smaller, is easy to deliver.EDB-FN targeting proteins peptide A16 of the present invention only has the length of 12 amino acid
Degree, easily delivering and distribution, so as to which the tumour cell for expressing EDB-FN albumen is detected and is followed the trail of, and did not caused
Quick reaction, be not easy to be removed by patients immune system.Overcome the prior art and difficult, Yi Yin is delivered using antibody molecule as targeting agent
Play allergic reaction, the duration short technical problem being quickly eliminated.
(2) affinity is high, is not easy to miss the target.EDB-FN targeting proteins peptide A16 of the present invention is by repeatedly to bacteriophage
Random peptide library progress repeated screening acquisition has EDB-FN albumen specific target tropism, the dodecapeptide of high affinity.Power
Learn test result indicates that, the Kd values of the A16 and EDB-FN of recombination expression have reached 1.92 × 10-7。
(3) better tolerance, not easy in inactivation.What EDB-FN targeting proteins peptide A16 of the present invention was simulated by linear structure
Mode realizes the combination to tumour cell EDB-FN, and the dependence to space conformation is relatively low, so as to be resistant to other functional activities point
Son is conjugated, and can be located at optional position such as N-terminal, C-terminal, the centre of conjugate.In addition, the EDB-FN targeting proteins peptides of the present invention
A16 can be used with multi-copy in tandem, so as to further increase targeting and reliability.
(4) specificity is high, can identify and with reference to the tumour cell of expression EDB-FN.The present invention is shown by phage random
Peptide library selection to EDB-FN targeting proteins peptides A16 can specifically bind expression EDB-FN U87 cells, without with reference to EDB-
The 293T cells of FN feminine genders.
Brief description of the drawings
By reading the detailed description of hereafter preferred embodiment, it is various other the advantages of and benefit it is common for this area
Technical staff will be clear understanding.Attached drawing is only used for showing the purpose of preferred embodiment, and is not considered as to the present invention
Limitation.In the accompanying drawings：
Fig. 1：PHAGE-ELISA result of the tests.
Abscissa 1-12 is the positive colony of picking,
Positive is positive control,
Negative is negative control,
Ordinate is 450nm absorbances,
The result shows that the 1st, 3,6,9, No. 11 clone is higher to the affinity of EDB-FN albumen, the external source being inserted into clone 1
12 peptides are A16.
Fig. 2：The combination power schematic diagram of dodecapeptide A16 and the EDB-FN albumen of recombination expression.
Three curves represent A16 concentration and dissociate schematic diagram as the combination of 80 μ g/mL, 40 μ g/mL and 20 μ g/mL respectively, survey
Obtaining combination power of the A16 to EDB-FN albumen is：Kd=1.92 × 10-7。
Fig. 3：The Cell immunofluorescence proof diagrams of dodecapeptide A16.
U87 cells are the positive cell of high expression EDB-FN albumen, and 293T cells are the negative cells of EDB-FN albumen, are tied
Fruit shows that A16 small peptides can specifically bind the EDB-FN albumen of cell surface, for the 293T cells of EDB-FN protein negatives
Do not combine then.
Embodiment
The illustrative embodiments of the disclosure are more fully described below with reference to accompanying drawings.Although this public affairs is shown in attached drawing
The illustrative embodiments opened, it being understood, however, that may be realized in various forms the disclosure without the reality that should be illustrated here
The mode of applying is limited.Conversely, there is provided these embodiments are to be able to be best understood from the disclosure, and can be by this public affairs
The scope opened completely is communicated to those skilled in the art.
The screening of embodiment one, EDB-FN targeting proteins peptides
This method is mixed and screened with dodecapeptide storehouse (NEB companies) using the restructuring EDB-FN albumen of immobilization, step
It is as follows：
1. Prokaryotic expression, purification EDB-FN albumen
The plasmid of the pGEX-4T-3-EDB-FN built is transferred in the expression bacterial strain of BL21,16 DEG C of inductions of IPTG
Expressing protein, GST column purification albumen, obtains the restructuring EDB-FN albumen that purity is more than 90%.
The screening of the bacteriophage dodecapeptide of 2.EDB albumen, step are as follows：
(1) method for using solid-phase screening, is diluted to 30-100ug/uL, coating arrives elisa plate by EDB albumen with 1xPBS
On bar, 100uL is added per hole, 4 DEG C are coated with overnight；
(2) PBS is washed three times, the skim milk of 300uL 4% is added per hole, when 37 DEG C of closings 2 are small；
(3) dodecapeptide phage display library is added after PBS washes three times and (there are about 1x1012CFU), when 37 DEG C 1 small；
(4) uncombined bacteriophage is suctioned out, PBS is added and washes 5-10 times (increasing washing times by wheel), then three are washed with PBST
All over the glycine-HCI solution of the rear PH=2.2 for adding 100uL, 37 DEG C 7 minutes；
(5) gently the bacteriophage of absorption is washed by piping and druming plate hole, then adds Tris-HCl solution (PH=8.8)
15uL, takes 10uL to measure titre after being sufficiently mixed；
(6) the ER2738 bacterium solutions that 200uL is stayed overnight to recovery are added in 20mL LB-Tet culture mediums, are put into shaking table, and 37
DEG C, 220rpm, 2h；When bacterium solution OD values reach 0.3-0.5, the half in above-mentioned elution storehouse is added into LB-Tet culture mediums,
37 DEG C, 220rpm, 4h；
(7) culture medium to be poured into 50ml test tubes, trim centrifugation (12000rpm, 10min) adds 4.5mlPEG-Nacl,
Mix, be put into ice chest, 4 DEG C of refrigerators preserve 2.5h；
(8) test tube in ice chest is taken out, trim centrifugation (12000rpm, 10min), removes supernatant, adds 1mLPBS, mixes,
EP pipes are transferred to, trim centrifugation (12000rpm, 2min), draws supernatant in new EP pipes, indicate title, time and operator
And 10uL is taken to measure titre；
(9) according to the titre after amplification, Phage amplification Kuku is taken (to there are about 1x1012CFU) eluted；
(10) after three-wheel elutriation, carried out at random from picked clones on the tablet for surveying titre with helper phage M13K07
Rescue, obtains the phasmid of displaying of target proteins, is verified with PHAGE-ELISA.
Table 1：PHAGE-ELISA experimental programs
PHAGE-ELISA experimental results are as shown in Figure 1.No. 1 clone of picking, upgrading grain carry out nucleic acid sequencing and determine bacteriophage
12 peptide of external source of middle insertion, and be A16 by the sequence designations of 12 peptide of external source.
Phagemid nucleic acid sequencing result such as SEQ ID NO:Shown in 2, wherein 7-42 nucleotide fragments codings are inserted
The external source dodecapeptide entered, the amino acid sequence by the dodecapeptide A16 being inserted into No. 1 phage clone of sequence analysis are：
ATYRLFQGVEVV(SEQ ID NO:1)。
Embodiment two, the combination power of dodecapeptide A16 and EDB-FN albumen measure
The nucleotide sequence of dodecapeptide A16 is inserted on PET28a plasmids, with EGFP coded sequence amalgamation and expressions, is transferred to
Recombinantly expressed in BL21, purify the fusion protein for obtaining dodecapeptide A16 and EGFP.
With the EZ-link Sulfo-NHS-LC-Biotin and Biothnylation of Thermo Scientific
Kits biotinylation kits carry out biotinylation to the EDB-FN albumen recombinantly expressed in embodiment one so that each EDB-FN
2 biotins on protein labeling.
Use instrument：Octet RED/QK measure biotinylation EDB-FN albumen and recombinate the combination power of A16-EGFP.
Biotinylated EDB albumen is diluted to 10ug/ml (per 200 μ L of hole), dodecapeptide A16 is diluted to 80 μ g/mL, 40
The BSA for the Tween-20+0.1% that μ g/mL and 20 μ g/mL (per 200 μ L of hole) dilution are PBS+0.1%, is loaded by table 2：
2 dodecapeptide A16 of table and EDB-FN protein bindings power measure scheme
| Experimental group | Control group | |
| Equilibrium liquid | PBST+BSA | PBST+BSA |
| Sensor coating buffer | EDB+PBST+BSA | EDB+PBST+BSA |
| Equilibrium liquid | PBST+BSA | PBST+BSA |
| Reaction solution | PBST+BSA+A16 | PBST+BSA |
| Dissociation solution | PBST+BSA | PBST+BSA |
Set detecting step and time as follows：
(1) PBST equilibrium stages, SA sensors react 60s in 200 μ L equilibrium liquids；
(2) Loading stages, SA sensors react 200s in 200 μ L diluted protein solutions；
(3) Association stages, SA sensors react 200s in 200 μ L A16 gradient dilution liquid；
(4) Dissociation stages, SA sensors react 200s in 200 μ L dissociation solutions.
Note：All stages all at 30 DEG C, 1000rpm.
The results are shown in Figure 2, measures combination power of the A16 to EDB-FN albumen and is：Kd=1.92 × 10-7S-1。
The Cell immunofluorescence verifications of embodiment three, dodecapeptide A16
Operating procedure is as follows：
(1) U87 and 293T cells are passaged to 6 orifice plates respectively, it is about 40% to cultivate to cell fusion degree；
(2) the dodecapeptide A16 for marking cy5.5 is added separately in U87 and 293T cells by the amount of 5ug, is put into dioxy
Change carbon incubator, after 10min taking-up observed with Laser Scanning Confocal Microscope.
The results are shown in Figure 3, and the U87 cell-specifics of height expression EDB-FN albumen are combined with dodecapeptide A16, and EDB-FN
The 293T cell surfaces of protein negative are then without the combination of A16.
The foregoing is only a preferred embodiment of the present invention, but protection scope of the present invention be not limited thereto,
Any one skilled in the art the invention discloses technical scope in, the change or replacement that can readily occur in,
It should be covered by the protection scope of the present invention.Therefore, protection scope of the present invention should be with the protection model of the claim
Subject to enclosing.
Sequence table
<110>Applicant's title Peking University
<120>A kind of high-affinity EDB-FN targeting proteins peptide and its application
<130>Nothing
<160> 2
<170> PatentIn version 3.5
<210> 1
<211> 12
<212> PRT
<213>Artificial sequence
<400> 1
Ala Thr Tyr Arg Leu Phe Gln Gly Val Glu Val Val
1 5 10
<210> 2
<211> 148
<212> DNA
<213>M13 bacteriophages
<400> 2
cactctgcta cgtatcggct ttttcagggg gtggaggttg ttggtggagg ttcggccgaa 60
actgttgaaa gttgtttagc aaaatcccat acagaaaatt catttactaa cgtctggaaa 120
gacgacaaac tagatgagcg aagtcccc 148
Claims (10)
1. a kind of EDB-FN targeting proteins peptide A16, its sequence such as SEQ ID NO:Shown in 1.
2. a kind of conjugate, includes targeting moiety and Functional portions, it is characterised in that the targeting moiety is claim 1 institute
State targeting peptides A16.
3. conjugate as claimed in claim 2, it is characterised in that the targeting containing one or more copies in the conjugate
Peptide A16.
4. conjugate as claimed in claim 2, it is characterised in that the Functional portions include being selected from by diagnostic flag, chemotherapy
The group of medicine, activated protein composition.
5. the conjugate as described in claim 2 to 4 is any, it is characterised in that can directly connect between each component of the conjugate
Connect or connected by connector, for example, between the Functional portions and the targeting moiety, between the multiple Functional portions,
It is directly connected between the multiple targeting moiety or is connected by connector, it is described to be directly connected to preferred peptide bond and be directly connected to.
6. a kind of nucleic acid, it is encoded：
(1) EDB-FN targeting proteins peptide A16 described in claim 1；Or
(2) any conjugate of claim 2 to 5.
7. a kind of nucleic acid construct, it includes nucleic acid described in claim 6.
8. a kind of host cell, it includes nucleic acid described in claim 6 or includes nucleic acid construct described in claim 7；It is described
Host is prokaryotic or eukaryotic, can express targeting peptides A16 described in claim 1 or claim 2 to 5 is described conjugated
Thing.
9. a kind of method for producing targeting peptides A16 described in claim 1 or claim 2 to 5 conjugate, including：
(1) host cell of claim 8 is prepared；
(2) host cell of incubation step (1) under the suitable conditions, makes its propagation；
(3) state of host cell and quantity reach when meeting production requirement, are being adapted to targeting peptides described in production claim 1
Host cell is cultivated under conditions of A16 or claim 2 to 5 conjugate；
(4) isolated and purified from host cell product described conjugated containing targeting peptides A16 described in claim 1 or claim 2 to 5
The fraction of thing.
10. the purposes of targeting peptides A16 described in claim 1 or claim 2 to 5 conjugate, its be used to prepare detection or
Diagnose the kit of EDB-FN albumen；Or it is used to prepare diagnosis or treatment and the medicine of the relevant tumour of EDB-FN abnormal proteins expression
Thing, it is described to include breast cancer, lung cancer, liver cancer, colorectal cancer, forefront with the relevant tumour of EDB-FN abnormal proteins expression
Gland cancer, head and neck cancer and lymthoma, glioma and melanoma.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111920700A (en) * | 2020-09-17 | 2020-11-13 | 北京达熙生物科技有限公司 | Preparation technology of stem cell exosome and application of stem cell exosome in medicines and cosmetics |
| CN114621325A (en) * | 2022-03-28 | 2022-06-14 | 哈尔滨医科大学 | Fibronectin targeted polypeptide and application thereof in promotion of tumor anoikis and chemotherapy sensitization |
| CN115819502A (en) * | 2022-10-12 | 2023-03-21 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | EDB-FN targeting polypeptide and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102791290A (en) * | 2009-12-15 | 2012-11-21 | 斯拉瓦克制药股份公司 | A novel vaccine that targets tumor vessels as an efficient tool in tumor therapy |
| WO2016022597A1 (en) * | 2014-08-04 | 2016-02-11 | Case Western Reserve University | Targeting peptides and methods of use |
-
2017
- 2017-10-17 CN CN201710966956.0A patent/CN107903307B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102791290A (en) * | 2009-12-15 | 2012-11-21 | 斯拉瓦克制药股份公司 | A novel vaccine that targets tumor vessels as an efficient tool in tumor therapy |
| WO2016022597A1 (en) * | 2014-08-04 | 2016-02-11 | Case Western Reserve University | Targeting peptides and methods of use |
| CN107001417A (en) * | 2014-08-04 | 2017-08-01 | 卡斯西部储备大学 | Targeting peptides and its application method |
Non-Patent Citations (2)
| Title |
|---|
| ZHENG HAN: "EDB Fibronectin Specific Peptide for Prostate Cancer Targeting", 《BIOCONJUGATE CHEMISTRY》 * |
| 龚锐: "纳米级靶向化疗药物的研究现状和应用前景", 《中国老年学杂志》 * |
Cited By (5)
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|---|---|---|---|---|
| CN111920700A (en) * | 2020-09-17 | 2020-11-13 | 北京达熙生物科技有限公司 | Preparation technology of stem cell exosome and application of stem cell exosome in medicines and cosmetics |
| CN114621325A (en) * | 2022-03-28 | 2022-06-14 | 哈尔滨医科大学 | Fibronectin targeted polypeptide and application thereof in promotion of tumor anoikis and chemotherapy sensitization |
| CN114621325B (en) * | 2022-03-28 | 2023-05-09 | 哈尔滨医科大学 | Fibronectin targeting polypeptide and application thereof in promoting tumor anoikis and chemosensitization |
| CN115819502A (en) * | 2022-10-12 | 2023-03-21 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | EDB-FN targeting polypeptide and application thereof |
| CN115819502B (en) * | 2022-10-12 | 2023-09-26 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | EDB-FN targeting polypeptide and application thereof |
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