Polypeptide with ovarian tumor targeted D-configuration and gene delivery system thereof

A technology for ovarian tumors and genes, applied in the direction of anti-tumor drugs, peptides, desipeptides, etc., can solve the problem of non-viral gene delivery system transfer that affects the targeting effect of polypeptide ligands, unstable polypeptides, and sequence polypeptide modifications that have not yet been seen. Transfection efficiency evaluation of anti-ovarian cancer effect and other issues, to achieve the effect of inhibiting growth, improving gene transfection efficiency, and high binding

Active Publication Date: 2017-05-10
THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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  • Abstract
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AI Technical Summary

Problems solved by technology

However, natural peptides are not stable in human blood and are easily degraded by proteases in serum, which affects the targeting effect of peptide ligands
[0006] At present, there is no report on the non-viral gene delivery system containing sequence polypeptide modification and its in vivo and in vitro transfection efficiency evaluation and anti-ovarian cancer effect

Method used

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  • Polypeptide with ovarian tumor targeted D-configuration and gene delivery system thereof
  • Polypeptide with ovarian tumor targeted D-configuration and gene delivery system thereof
  • Polypeptide with ovarian tumor targeted D-configuration and gene delivery system thereof

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Embodiment Construction

[0026] 1) Synthesis of nanocarrier materials and 1H-NMR structure identification

[0027] Quantitatively weigh D-type polypeptide D (FTCTKQIKPRAPDKYVLDRTY) and NHS-PEG-MAL to make the molar ratio 4:1. After the DMF is fully dissolved, stir the reaction with magnetic force at room temperature for 6 hours, add dH2O to dilute the reaction solution 5 times to stop the reaction; then place the solution in an Amicon Ultra-4 (3KDa) ultrafiltration centrifuge tube and centrifuge at room temperature at 3000rpm for 45min until the liquid remains about 1ml Supplement 4mldH2O at the same time, and repeat this 10 times; then the solution was lyophilized, and the product obtained was named D-FP21-PEG-MAL. Dissolve 200mgPEI in 100mldH2O, after fully dissolved, adjust the pH to 7.4 with 1N hydrochloric acid; take out the corresponding volume of PEI, add D-FP21-PEG-MAL to make the mass ratio 0.833:1. The mixed solution was magnetically stirred at room temperature for 24 hours to react; after ...

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Abstract

The invention provides a polypeptide with ovarian tumor targeted D-configuration and a gene delivery system thereof. The L-polypeptide YTRDLVYKDPARPKIQKTCTF inverted sequence is replaced by D-configuration amino acid so as to obtainD(FTCTKQIKPRAPDKYVLDRTV)sequence polypeptide as targeting molecules, and the gene is targeted and delivered to ovarian carcinoma cells by using the high compatibility with FSHR; and theD(FTCTKQIKPRAPDKYVLDRTY)is decorated to the PEI-PEG surface so as to obtain aD(FTCTKQIKPRAPDKYVLDRTY)-PEG-PEI(D-FP21-pp)gene vector, wherein the gene vector encapsulates a therapeutic gene Gro-oshRNA. The gene transfection efficiency can be greatly improved, and the anti-tumor rate of the naked mouse subcutaneous tumor can be remarkably improved.

Description

technical field [0001] The invention relates to a D-configuration polypeptide and a gene delivery system, especially a D-type polypeptide with high activity binding to ovarian cancer cells and ovarian cancer-targeting gene delivery system and its modified gene delivery system. Background technique [0002] The mortality rate of ovarian cancer ranks among the top five among women's cancer deaths, and ranks first among gynecological malignancies. Most ovarian cancer patients are diagnosed at an advanced stage, and the treatment of advanced ovarian cancer has always been a very difficult problem. Although the improvement of surgery, the launch of new drugs, and the introduction of new chemotherapy regimens have improved the treatment effect to a certain extent, the 5-year survival rate has not yet been significantly improved. Chemotherapy is an important means of treatment for advanced ovarian cancer, but most advanced patients relapse or drug resistance after treatment, leadi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00C12N15/87A61K31/7088A61K47/42A61K47/32A61K47/34A61P35/00
CPCA61K31/7088A61K47/32A61K47/34A61K47/42C07K14/00C12N15/87
Inventor 徐丛剑张晓燕张梦宇张明星蔡青青尧良清
Owner THE OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIV
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