Histamine-modified agmatine-based linear-polymer transgenic carrier and preparation method and applications thereof

An arginine-based linear, transgenic vector technology, applied in the field of transgenic vectors and their preparation, can solve the problems of complex escape ability, poor biocompatibility, low transfection efficiency, etc., to increase endosome escape ability , mild synthesis conditions and simple preparation methods

Inactive Publication Date: 2012-08-15
樊世田
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, cationic polymers have become an important part of non-viral gene carriers, but when cationic polymers are used as gene carriers, there are still some problems, such as poor biocompatibility, toxicity, and the formation of complexes from the connotation. The ability of body escape is weak and the transfection efficiency is low

Method used

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  • Histamine-modified agmatine-based linear-polymer transgenic carrier and preparation method and applications thereof
  • Histamine-modified agmatine-based linear-polymer transgenic carrier and preparation method and applications thereof
  • Histamine-modified agmatine-based linear-polymer transgenic carrier and preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Get a 50ml round bottom flask, add agmatine sulfate (1.71g, 7.5mmol), histamine dihydrochloride (0.46g, 2.5mmol) and water (10ml) into the flask (ie agmatine sulfate The molar ratio to histamine dihydrochloride is 3 / 1), and stir evenly until it becomes a transparent liquid. About 1 ml of sodium hydroxide solution (4M) was added dropwise to adjust the pH value of the reaction system to about 10. Under vigorous stirring, 1 ml of glycidyl methacrylate (ρ=1.074 g / ml, 7.6 mmol) was slowly dropped into the reaction system, and the reaction was carried out at 35° C. for 24 hours. Extract the reaction solution with ether, collect the lower layer liquid into a 50ml round bottom flask, adjust the pH value of the system to about 5 with 1ml hydrochloric acid solution (4M), add ammonium persulfate (12mg, 0.05mmol) at 65°C under oxygen-free nitrogen Random polymerization under protected conditions for 24 hours. The reaction product was dialyzed in deionized water with a dialysis ba...

Embodiment 2

[0030]Get a 50ml round bottom flask, add agmatine sulfate (1.14g, 5mmol), histamine dihydrochloride (0.92g, 5 mmol) and water (10ml) in the flask (ie agmatine sulfate and The molar ratio of histamine dihydrochloride is 2 / 2), and stir until it becomes a transparent liquid. About 2ml of sodium hydroxide solution (4M) was added dropwise to adjust the pH value of the reaction system to about 10. Under vigorous stirring, 1 ml of glycidyl methacrylate (ρ=1.074 g / ml, 7.6 mmol) was slowly dropped into the reaction system, and the reaction was carried out at 35° C. for 24 hours. Extract the reaction solution with ether, collect the lower layer liquid into a 50ml round bottom flask, adjust the pH value of the system to about 5 with 2ml hydrochloric acid solution (4M), add ammonium persulfate (12mg, 0.05mmol) at 65°C under oxygen-free nitrogen Random polymerization under protected conditions for 24 hours. The reaction product was dialyzed in deionized water with a dialysis bag (molecul...

Embodiment 3

[0033] Get a 50ml round bottom flask, add agmatine sulfate (0.57g, 2.5mmol), histamine dihydrochloride (1.38g, 7.5mmol) and water (10ml) into the flask (ie agmatine sulfate The molar ratio to histamine dihydrochloride is 1 / 3), and stir evenly until it becomes a transparent liquid. About 3ml of sodium hydroxide solution (4M) was added dropwise to adjust the pH value of the reaction system to about 10. Under vigorous stirring, 1 ml of glycidyl methacrylate (ρ=1.074 g / ml, 7.6 mmol) was slowly dropped into the reaction system, and the reaction was carried out at 35° C. for 24 hours. Extract the reaction solution with ether, collect the lower layer liquid into a 50ml round bottom flask, adjust the pH value of the system to about 5 with 2ml hydrochloric acid solution (4M), add ammonium persulfate (12mg, 0.05mmol) at 65°C under oxygen-free nitrogen Random polymerization under protected conditions for 24 hours. The reaction product was dialyzed in deionized water with a dialysis bag...

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Abstract

The invention discloses a histamine-modified agmatine-based linear-polymer transgenic carrier and a preparation method and applications thereof. The transgenic carrier is prepared through reacting open loops of epoxy groups of glycidyl methacrylate with amino end groups of agmatine and histamine, chaining the agmatine and the histamine to the glycidyl methacrylate through chemical bonds, initiating a modified glycidyl methacrylate monomer to carry out free-radical atactic polymerization, and finally chaining the electropositive agmatine and the histamine with a proton buffering function to macromolecule chains. The agmatine carrier has good biocompatibility and promotes the transmembrane capacity of composites. The modification of the histamine increases the endosome escape capability of composites on the premise of not affecting the cell toxicity of the carrier, thereby effectively improving the efficiency and properties of the agmatine as a transgenic carrier; and the carrier can be used as an efficient non-viral gene carrier for gene therapy, realizes the improvement on the gene transfection efficiency of the agmatine carrier, and extends the role of the in-vivo circulation time.

Description

technical field [0001] The invention relates to a transgene carrier and a preparation method thereof, in particular to a histamine-modified agmatine-based linear polymer transgene carrier and a preparation method thereof. Background technique [0002] Gene therapy refers to the introduction of human normal genes or therapeutic genes into human target cells in a certain way to correct gene defects or exert therapeutic effects. The vectors used in gene therapy mainly include viral vectors and non-viral vectors. Viral vectors have made some breakthroughs in gene therapy, but in the process of clinical application, their immunogenicity and potential carcinogenicity are still major hidden dangers that are difficult to overcome. As another way of gene delivery, non-viral vectors have been widely studied, which mainly include naked DNA, liposomes, and cationic polymers. [0003] As a kind of non-viral vector, cationic polymer not only has the advantages of non-viral vector (ie lo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F220/36C12N15/87
Inventor 刘文广李咏懋杨建海王玮
Owner 樊世田
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