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Multifunctional specific DNA hybridization-gated mesoporous silica gene carrier and preparation method and application thereof

A technology of mesoporous silica and gene carrier, applied in recombinant DNA technology, other methods of inserting foreign genetic materials, pharmaceutical formulations, etc., can solve the lethality of tumor cells and other problems

Pending Publication Date: 2019-08-09
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Once delivered to tumor cells by DNA-hybrid-gated nanocarriers for recognition and endocytosis, the overexpressed endogenous miRNA acts as an unlocked nanocarrier through competitive hybridization with DNA hybrids and can control drug release via microRNA , resulting in sustained lethality of tumor cells

Method used

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  • Multifunctional specific DNA hybridization-gated mesoporous silica gene carrier and preparation method and application thereof
  • Multifunctional specific DNA hybridization-gated mesoporous silica gene carrier and preparation method and application thereof
  • Multifunctional specific DNA hybridization-gated mesoporous silica gene carrier and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Step 1) The preparation method of mesoporous silica nanoparticles using CTAB template method is as follows:

[0050] 1) Prepare 20 ml of a solution of 1% cetyltrimethylammonium bromide (CTAB) in the reaction vessel;

[0051] 2) Add 5 ml of absolute ethanol and 100 microliters of ethylene glycol, stir and react for 30 minutes under heating conditions of 400 rpm and 60°C;

[0052] 3) Add 300 microliters of ethyl orthosilicate to the reaction vessel and stir for 10 minutes under heating at 700 rpm and 70°C, then turn off the heating and then stir for 30 minutes at 400 rpm;

[0053] 4) After the reaction is over, centrifuge at 12,000 rpm for 20 minutes, and wash the precipitate with absolute ethanol. After the product is vacuum dried, silica nanoparticles are obtained;

[0054] 5) Take 10-20 mg of the prepared silica nanoparticles, prepare a solution of 20 mg / ml with absolute ethanol and transfer to a reaction vessel;

[0055] 6) Add 0.6 g of sodium chloride to the reaction vessel, st...

Embodiment 2

[0075] Step 1) The steps of the preparation method of mesoporous silica nanoparticles are as follows:

[0076] 1) Mesoporous silica nanoparticles are prepared by the CTAB template method: 1) Prepare 15 ml of a 1% cetyltrimethylammonium bromide (CTAB) solution in a reaction vessel;

[0077] 2) Add 5 ml of absolute ethanol and 100 microliters of ethylene glycol, stir and react for 10 minutes at 500 rpm and heating at 60°C;

[0078] 3) Add 200 microliters of ethyl orthosilicate to the reaction vessel and stir for 10-20 minutes under heating at 60°C at 600 revolutions / min, then turn off the heating and then stir for 30 minutes at 450 revolutions / min. ;

[0079] 4) After the reaction is over, centrifuge at 12,000 rpm for 20 minutes, and wash the precipitate with absolute ethanol. After the product is vacuum dried, silica nanoparticles are obtained;

[0080] 5) Take 10 mg of the prepared silica nanoparticles, prepare a 5 mg / ml solution with absolute ethanol and transfer to a reaction vessel;...

Embodiment 3

[0101] Step 1) The steps of the preparation method of mesoporous silica nanoparticles are as follows:

[0102] 1) Mesoporous silica nanoparticles are prepared by the CTAB template method: 1) Prepare 10-20 ml of a 1.5% cetyltrimethylammonium bromide (CTAB) solution in a reaction vessel;

[0103] 2) Add 7 ml of absolute ethanol and 200 microliters of ethylene glycol, stir and react for 15 minutes under heating conditions of 500 rpm and 50°C;

[0104] 3) Add 250 microliters of ethyl orthosilicate into the reaction vessel and stir for 15 minutes under heating at 65°C at 650 rpm, then turn off the heating and then stir for 30 minutes at 500 rpm;

[0105] 4) After the reaction is over, centrifuge at 12,000 rpm for 25 minutes, and wash the precipitate with absolute ethanol. After the product is vacuum dried, silica nanoparticles are obtained;

[0106] 5) Take 10 mg of the prepared silica nanoparticles, prepare a solution of 15 mg / ml with absolute ethanol and transfer to a reaction vessel;

[01...

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Abstract

The invention relates to a multifunctional specific DNA hybridization-gated mesoporous silica gene carrier and a preparation method and application thereof. A mesoporous silica particle is adopted asa carrier body to produce particles with the particle size of 50-100 nm; the surface is modified with anchoring DNA, and a gated structure is formed on a DNA hybrid so that the nanoparticles can achieve the release of drugs on specific targets. At the same time, the surfaces of the particles are modified with polyetherimide loaded plasmid, so that a drug and gene combined treatment effect is achieved. A synthesis process of the carrier is simple, free of toxicant, fast and large in yield. In an in-vitro cytotoxicity test, the cell survival rate is 75.1-95%. The multifunctional specific DNA hybridization-gated mesoporous silica gene carrier has high biosafety.

Description

Technical field [0001] The invention relates to a multifunctional specific DNA hybrid-gated mesoporous silica gene carrier and its preparation method and application. Background technique [0002] The design of an ideal drug delivery system with specific recognition and zero premature release, especially the controlled and specific release triggered by unique endogenous stimuli, has always been a huge challenge in the design of nanocarriers. Mesoporous silica nanoparticles (MSNPs) are widely used in drug delivery systems due to their controllable mesoporous structure, high specific surface area, and good biocompatibility. At the same time, the rich modifiable groups on its surface can be used to develop its zero-premature release and space-time controlled release functions. However, conventional drug-loaded mesoporous silica nanoparticles have the problem of drug release during in vitro storage and in vivo transportation, which causes a large amount of drug loss and may produce ...

Claims

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Application Information

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IPC IPC(8): C12N15/87A61K47/04A61K47/26
CPCC12N15/87A61K47/02A61K47/26
Inventor 常津杨涵武晓丽赵杰段玥董国修
Owner TIANJIN UNIV
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