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Nanometer genetic medicine resistant to tumors and preparation method and application thereof

A genetic drug and anti-tumor technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of nano-drugs without targeting and pH responsiveness, and achieve improved targeting and better treatment Good effect, biocompatibility

Active Publication Date: 2018-06-12
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] CN106890343A discloses a polypeptide nano gene carrier complex with tumor targeting effect, which is composed of positively charged nano gene carrier, gene drug and tumor targeting antibody, and has a certain targeted therapeutic effect, but the nano The gene carrier complex does not have pH responsiveness, and is limited to antibody targeting, which has certain limitations; CN104940949A discloses an anti-tumor polypeptide nano drug and its preparation method and application, including amphiphilic anti-tumor polypeptide and acid response Sexual functional molecules, but this nano drug is not targeted, and only uses polypeptide as a carrier, which limits the application

Method used

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  • Nanometer genetic medicine resistant to tumors and preparation method and application thereof
  • Nanometer genetic medicine resistant to tumors and preparation method and application thereof
  • Nanometer genetic medicine resistant to tumors and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] In this embodiment, the anti-tumor nanogene drug is prepared by the following method, which is:

[0083] Select (Robert Qing Miao et al., PNAS, 2006,103(29):10997-11002) to provide the Mouse NgBR siRNA double-stranded nucleic acid base sequence (sequence starting from the 5' end is: ACAUUAGCGUCACGACCAdTdT, the corresponding sequence of the other chain is: UGGUCGUAGACGCUAAUGUdTdT) as a therapeutic small interfering RNA nucleic acid molecule, prepared nanomicelle according to the mature microemulsion method reported in the literature, and electrostatically adsorbed therapeutic NgBR siRNA through positively charged PEI, Then, a plurality of DMMAs are connected through amino groups (including terminal amino groups and side chain amino groups) on the PEI to obtain amphiphilic anti-tumor cationic polymer micelles coupled with acid-responsive functional molecules. The synthesis process is as follows:

[0084] (1) PEI-(PLGA) for the synthesis of PEI-PLGA-DMMA cationic polymer ...

Embodiment 2

[0093] In the present embodiment, through the same synthesis method and steps as in Example 1, the cationic polymer nanomicelle PEI-(PLGA) 2 The acid-responsive DMMA molecule was coupled to the acid-responsive cationic polymer nanometer gene carrier coupled with DMMA. The anti-tumor nanogene drug system was obtained through the same adsorption process of therapeutic NgBR siRNA as in Example 1.

[0094] It was confirmed by means of Fourier transform infrared spectroscopy that the structure of the nanomicelle coupled with DMMA cationic polymer obtained in this example is: PEI-PLGA-DMMA.

[0095] The shape and particle size of the obtained anti-tumor nano-gene drug system were characterized by transmission electron microscope and laser particle size analyzer. The distribution is 60-150nm, the average particle size is about 130nm, and the dispersion index (PDI) is 0.083.

Embodiment 3

[0097] In this embodiment, the protective effect of self-assembled nanoparticle of anti-tumor nanogene drug on its surface adsorbed siRNA in neutral Tris-HCl buffer solution containing 10% serum was determined.

[0098] Incubate the anti-tumor nanogene drug system samples obtained in Example 1 with neutral Tris-HCl buffer solution containing 10% serum for 0h, 1h, 3h, 6h, 12h, 24h, 48h, and take 10 μL samples at each time point Add it to the pre-prepared agarose gel loading well, mix 10 μL of the system with the corresponding proportion of syber green dye and loading buffer, and then run the gel electrophoresis under the condition of voltage 100V. After about 10 minutes, place the gel in In the bio-rad biological imager, select the ultraviolet mode for imaging. Such as image 3 As shown, after incubation with the neutral Tris-HCl buffer containing 10% serum for different times, the content of siRNA remained consistent compared with the control group, which indicated that in th...

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Abstract

The invention provides a nanometer genetic medicine resistant to tumors and a preparation method and application thereof. The nanometer genetic medicine resistant to tumors comprises amphipathic cationic polymers, acid response functional molecules and small interference RNA, wherein the acid response functional molecules are coupled with the amphipathic cationic polymers, and the small interference RNA adheres to the surfaces of the amphipathic cationic polymers through electrostatic adsorption. The provided nanometer genetic medicine resistant to tumors is great in biocompatibility, low in toxic and side effect and high in bioavailability and has acid pH responsiveness and electric charge overturning performance; the nanometer genetic medicine resistant to tumors has a broad applicationprospect and a high application value in preparation of medicine resistant to tumors or in preparation of medicine for treating vascular normalization.

Description

technical field [0001] The invention belongs to the field of nano-medicine, and relates to an anti-tumor nano-gene drug and its preparation method and application. Background technique [0002] Blood vessels are an important component of the solid tumor microenvironment. Since 1971, Professor Judah Folkman of Harvard University pointed out the importance of the formation of blood vessels inside solid tumors for their growth and distant metastasis, and proposed that blocking the internal blood vessels of tumors would lead to severe hypoxia and nutrient deficiency in tumor tissues, which would lead to tumor necrosis. A large number of scientists have begun to study the mechanism of tumor angiogenesis, the screening of targets, and the development of blood vessel blocking drugs. According to research reports, more than 40 kinds of molecules are involved in the process of tumor angiogenesis, and 10 kinds of drugs targeting vascular endothelial growth factor and its receptors h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/34A61K47/12A61K31/713A61P35/00
CPCA61K9/1075A61K31/713A61K47/12A61K47/34
Inventor 丁艳萍聂广军王斌
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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