Polymethacrylate, preparation method and application thereof

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...

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)

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