Polymethacrylate, preparation method and application thereof

A methacrylate and dimethylamino technology, applied in the application field of polymethacrylate in gene therapy, can solve the problem of unfavorable transport in vivo, damage to cell membrane structure, cell transfection and no research on terminal thiol oligomers. Cytotoxicity, etc.

Inactive Publication Date: 2009-05-13
SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Second, the cationic properties of the nano-gene complex combine with the negatively charged components of body fluids, which is not conducive to in vivo transport; the electrostatically assembled nano-complex prevents the release of DNA, which is not conducive to the expression of encoded genes; the positive charge of the complex also destroys the membrane structure of cells, produce hemolytic toxicity
The product reported in this literature is only a linear polymer with controllable structure. The transfection and cytotoxicity of rPDMAEMA cross-linked by disulfide bonds were studied, but the cell transfection and cytotoxicity of terminal thiol oligomers were not studied. Fluorescein The enzyme has 3-4 times higher transfection activity for rPDMAEMA / plasmid gene complex reporter gene expression than polymethacrylate (PDMAEMA)

Method used

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  • Polymethacrylate, preparation method and application thereof
  • Polymethacrylate, preparation method and application thereof
  • Polymethacrylate, preparation method and application thereof

Examples

Experimental program
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Effect test

example 1

[0087] Example 1: Synthesis of 1,3,5-tris(2-(thiobenzenesulfonyl-2-propyl))benzene

[0088] In a 500ml round bottom flask, add 100ml carbon tetrachloride, 0.1mol1,3,5-triisopropylbenzene, 0.45mol N-bromosuccinimide (NBS), 20mg benzoyl peroxide catalyst, reflux After 48 hours, filter, wash with saturated sodium bicarbonate three times, dry over anhydrous magnesium sulfate, and distill off the solvent to obtain a yellow oily liquid with a yield of 85%. Add the yellow oily liquid to 100ml of chloroform solvent, add 0.45mol of thiobenzenesulfonyl magnesium bromide, reflux for 48h, separate by column chromatography, and distill off the solvent to obtain 1,3,5-tri(2-(thiobenzene Sulfonyl-2-propyl))benzene.

example 2

[0089] Example 2: Synthesis of 1,3,5-tris(2-(xanthogenyl-2-propyl))benzene

[0090] Add 100ml carbon tetrachloride, 0.1mol1,3,5-triisopropylbenzene, 0.45mol N-bromosuccinimide, 20mg benzoyl peroxide catalyst into a 500ml round bottom flask, reflux for 48h, filter, Wash with saturated sodium bicarbonate, dry over anhydrous magnesium sulfate, and distill off the solvent to obtain a yellow oily liquid with a yield of 80%. Add the yellow oily liquid to 100ml of chloroform solvent, add sodium ethyl xanthate, reflux for 48h, separate by column chromatography, and distill off the solvent to obtain 1,3,5-tris(2-(ethyl xanthate-2 -Propyl))benzene.

example 3

[0091] Example 3: Synthesis of TEX-PDMAEMA

[0092] In a 5ml round bottom flask, add DMAEMA (1g), azobisisobutyronitrile (4mg), 1,3,5-tris(2-(thiobenzenesulfonyl-2-propyl))benzene (80mg) and 2ml of tetrahydrofuran, fully deoxygenated, vacuum-sealed, and placed in a water bath at 60°C for 48 hours. The 1,3,5-terminal trisulfonate polymer—TEX-PDMAEMA was obtained, and excess hexane was added to precipitate and isolate the product. for polymer 1 H NMR characterization, D 4 -Methanol and D-chloroform as solvents.

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Abstract

The invention relates to reductive cation polymethacrylate, a preparation method thereof, application of the polymethacrylate to establishment of gene nano-complexes and application of the polymethacrylate to gene therapy. The method comprises the following steps: 1, 3, 5-triisopropylphenyl is taken as a raw material and reacts with N- bromosuccinimide and potassium ethyl xanthate to obtain substituted 1, 3, 5- triisopropylphenyl potassium ethyl xanthate; and the substituted 1, 3, 5- triisopropylphenyl potassium ethyl xanthate is catalyzed by azo-bis-iso-butyrynitrile, and subjected to reversible addition-broken strand transfer polymerization, aminolysis and oxidation reaction with 2-(dimethylamino ethyl)metacrylic acid ester to obtain poly (1, 3, 5-three-terminal sulfhydryl (2-propyl phenyl -2-(dimethylamino)ethyl)) methacrylic acid ester) and disulfide bond crosslinking products of the poly (1, 3, 5-three-terminal sulfhydryl (2-propyl phenyl -2-(dimethylamino)ethyl)) methacrylic acid ester). The polymethacrylate can condense plasmid genes into nano complexes; the transfection efficiency of HEK293T cells and Hella cells is more than 30 percent; the toxicity is low; and the survival rate of the cells is more than 80 percent.

Description

technical field [0001] The invention relates to a reducing cationic polymethacrylate carrier for gene therapy and its preparation method. The invention also relates to the application of the polymethacrylate in the construction of gene nanocomposites and the use of the polymethacrylate in the construction of gene nanocomposites. Applications in gene therapy. Background technique [0002] The cationic polymer carrier in the non-viral vector has excellent DNA binding ability, has the advantages of non-immunogenicity, large loading capacity, easy preparation, etc., and is convenient for targeting and biological practicability modification. important research object. Many cationic polymer carriers have been reported in the literature, such as polylysine, polyethyleneimine, polyamidoamine, polyurethane, chitosan, etc. The cationic properties of the cationic polymer gene carrier have a double impact on the transfection efficiency: first, the cationic polymer can provide the powe...

Claims

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Application Information

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IPC IPC(8): C08F120/34C08F2/38C08F8/00C08J3/24A61K48/00A61K47/32
Inventor 于伯章马继飞李文新
Owner SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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