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CP-iRGD polypeptide, iDPP nanoparticles, and drug-loading complex, preparation method and applications thereof

A nanoparticle and composite technology, applied in the field of medicine, can solve the problems of high difficulty and low transfection efficiency, and achieve high transfection ability, low cytotoxicity, and good DNA binding ability

Active Publication Date: 2018-08-03
SICHUAN UNIV
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Problems solved by technology

When PEG-PLA nanoparticles are used in the gene transfer system, it is difficult to load genes with mPEG-PLA nanoparticles alone, and the transfection efficiency is low

Method used

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  • CP-iRGD polypeptide, iDPP nanoparticles, and drug-loading complex, preparation method and applications thereof
  • CP-iRGD polypeptide, iDPP nanoparticles, and drug-loading complex, preparation method and applications thereof
  • CP-iRGD polypeptide, iDPP nanoparticles, and drug-loading complex, preparation method and applications thereof

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preparation example Construction

[0058] The present invention also provides a method for preparing the above-mentioned CP-iRGD polypeptide, comprising the following steps:

[0059] A, take Polyethylene Glycol and stearic acid as raw material reaction and separate and purify to obtain C18-PEG-OH;

[0060] B. Reaction of C18-PEG-OH and Fmoc-phenylalanine to obtain C18-PEG-Phe-Fmoc;

[0061] C. Remove the C18-PEG-Phe-Fmoc protecting group Fmoc to obtain C18-PEG-Phe-NH 2 ;

[0062] D. C18-PEG-Phe-NH 2 Reaction with 3-maleimide propionate N-hydroxysuccinimide ester to obtain C18-PEG-BMPS;

[0063] E. The target compound C18-PEG-iRGD was obtained by reacting C18-PEG-BMPS and iRGD through maleimide group and sulfhydryl group.

[0064] Preferably, in step C of the above preparation method, 1,8-diazabicyclo[5.4.0]undec-7-ene is used to remove the C18-PEG-Phe-Fmoc protecting group Fmoc.

[0065] Preferably, in step E of the above preparation method, the solvent used in the reaction is formed by mixing PBS buffer w...

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Abstract

The invention belongs to the field of medicine, and specifically relates to a CP-iRGD polypeptide, iRGD-DOTAP-mPEG-PLA nanoparticles, and a drug-loading complex, a preparation method and applicationsthereof. The technical problem to be solved by the present invention is to provide a new modification way form modifying a mPEG-PLA diblock copolymer, wherein an amphiphilic mPEG-PLA diblock copolymeris modified with a positively charged amphiphilic substance DOTAP and a modified CP-iRGD polypeptide having tumor targeting effect, and a self-assembly method is used to prepare the novel degradablegene vector iRGD-DOTAP-mPEG-PLA nanoparticles, ie., iDPP nanoparticles, wherein the iRGD-DOTAP-mPEG-PLA nanoparticles have good DNA binding ability, can effectively introduce gene plasmid into tumor cells, and have advantages of high transfection rate, low cytotoxicity and the like.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to CP-iRGD polypeptide, iDPP nanoparticle, drug-loaded complex, preparation method and application thereof. Background technique [0002] The gene transfer system has important applications in gene function research and gene therapy. Currently used gene transfer systems mainly include two categories: viral vectors and non-viral vectors. Viral vectors include retroviral vectors, lentiviral vectors, adenoviral vectors and adenoviral-associated vectors, which can efficiently deliver therapeutic genes into cells, but their large-scale production is difficult, and the gene capacity that can be delivered is small, which can easily cause immune reactions , a potential biosafety risk. Non-viral gene carriers include liposomes, cationic nanoparticles, inorganic nanoparticle carriers, etc., which have the characteristics of low immunogenicity, good safety, and easy large-scale production...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K1/113C07K1/06A61K47/62A61K47/69A61K47/34A61K47/54A61K48/00A61P35/00A61P35/04
CPCA61K47/34A61K48/0041A61K48/0075C07K7/06Y02P20/55A61K47/54A61K47/62A61K47/69A61K48/00A61P35/00A61P35/04C07K1/06C07K1/113
Inventor 苟马玲魏于全罗丽杨玉屏陈雨文
Owner SICHUAN UNIV
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