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Cationic brush block copolymer and preparation method as well as application thereof

A block copolymer, cationic technology, applied in cationic brush-shaped block copolymer, its preparation field, can solve the problem of increasing the toxicity of the carrier, achieve good application value, reduce toxicity, improve the effect of distribution

Inactive Publication Date: 2013-04-24
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the electrostatic interaction between the cationic carrier and DNA limits the dissociation and release of the gene after entering the nucleus, and excessive positive charges will increase the toxicity of the carrier

Method used

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  • Cationic brush block copolymer and preparation method as well as application thereof
  • Cationic brush block copolymer and preparation method as well as application thereof
  • Cationic brush block copolymer and preparation method as well as application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment one: ATRP macromolecular initiator polyhydroxyethyl methacrylate PHEMA 33 Synthesis of -Cl

[0044] Put the branch tube round bottom flask in an oven at 120 ℃ to dry, then plug it with a ground glass stopper, pump it to cool until it reaches room temperature, fill it with argon after three times of filling and degassing. The monomer hydroxyethyl methacrylate (HEMA) (4.1 g, 31.50 mmol) was dissolved in methanol (10 mL) and added to the vial, and the small molecule initiator methyl α-bromopropionate (119 mu L, 1.05 mmol), ligand 2,2′-bipyridine (328.0 mg, 2.1 mmol), cuprous chloride (104.0 mg, 1.05 mmol) with a purity of 99.99% were added to the above mixed system, and argon was introduced Protect. Raise the temperature to 30°C, and maintain this temperature, stir with magnetic force, and react for 10-12 hours.

[0045] Methanol was added to dilute the reaction product, and it was contacted with air while stirring to terminate the reaction. After the solut...

Embodiment 2

[0047] Example 2: Diblock copolymer PHEMA with side groups containing hydroxyl groups 33 - b -PDMAEMA 66 Synthesis

[0048] Put the branch tube round bottom flask in an oven at 120 ℃ to dry, then plug it with a ground glass stopper, pump it to cool down until it reaches room temperature, fill and discharge the argon gas three times, and then continue to fill the glass bottle with argon gas. The macroinitiator PHEMA that embodiment one prepares 33 -Cl (2.2 g, 0.5 mmol) dissolved in methanol (15 mL) was added to the vial, the ligand 2,2′-bipyridine (156.2 mg, 1.0 mmol), the monomer methacrylic acid-2-(dimethyl Amino)ethyl ester (DMAEMA) (4.6 g, 30 mmol) and cuprous chloride (49.5 mg, 0.5 mmol) with a purity of 99.99% were added to the above mixed system, and argon protection was introduced. Raise the temperature to 35°C, and maintain this temperature, stir with magnetic force, and react for 24-28 hours.

[0049] Methanol was added to dilute the reaction product, and it was ...

Embodiment 3

[0051] Example 3: Diblock copolymer PHEMA with side groups containing hydroxyl groups 33 - b -PDMAEMA 50 Synthesis

[0052] Put the branch tube round bottom flask in an oven at 120 ℃ to dry, then plug it with a ground glass stopper, pump it to cool down until it reaches room temperature, fill and discharge the argon gas three times, and then continue to fill the glass bottle with argon gas. The macroinitiator PHEMA that embodiment one prepares 33-Cl (2.2 g, 0.5 mmol) dissolved in methanol (15 mL) was added to the vial, the ligand 2,2′-bipyridine (156.2 mg, 1.0 mmol), the monomer methacrylic acid-2-(dimethyl Amino)ethyl ester (DMAEMA) (3.8 g, 25 mmol) and cuprous chloride (CuCl, 49.5 mg, 0.5 mmol) with a purity of 99.99% were added to the above mixed system, and argon gas protection was introduced. Raise the temperature to 35°C, and maintain this temperature, stir with magnetic force, and react for 24-28 hours.

[0053] Methanol was added to dilute the reaction product, an...

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Abstract

The invention discloses a cationic brush block copolymer and a preparation method as well as an application of the block copolymer. The cationic brush block copolymer of which a side chain contains biodegradable polyphosphonate is prepared by combining an ATRP (atom transfer radical polymerization) with an ROP (ring-opening polymerization) for the first time; and the preparation method comprises the following steps of: firstly, carrying out ATRP polymerization reaction on hydroxyethyl methacrylate by a micromolecle ATRP initiator, thus obtaining macromolecule with bromine or chlorine substituent at the tail end; carrying out ATRP polymerization reaction between the macromolecule serving as a macromolecular ATRP initiator and a monomer sensitive to PH to obtain a PH response diblock copolymer; and carrying out ring-opening and graft copolymerization on a ring phosphate monomer by using hydroxyl on the side group of the diblock copolymer, thus obtaining the cationic brush block copolymer of which the side chain contains polyphosphonate. The novel cationic brush block copolymer of which the side chain contains polyphosphonate has good biocompatibility and biodegradability and low toxicity, so that the block copolymer can be used as a gene vector, and has good application prospect in a biomedicine.

Description

technical field [0001] The invention belongs to the field of biomedical polymer materials, and in particular relates to a cationic brush-shaped block copolymer, its preparation method and its application as a gene carrier. Background technique [0002] Today, genomics has made breakthroughs in the treatment of congenital and acquired diseases, and gene therapy has become one of the most active research fields. 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, so as to achieve the purpose of treating diseases. Constructing a vector with good biocompatibility, biodegradability, high safety, high transfection efficiency and high expression level, so that the target gene can be expressed in target cells in a safe, controllable, efficient and stable way is the research of gene therapy. an important direction. [0003] Gene carriers currently used for g...

Claims

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Application Information

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IPC IPC(8): C08F293/00C08F220/28C08F220/34C08F8/40C08F6/10C08F6/12C12N15/87
Inventor 倪沛红郝莹何金林张明祖刘坚张洋
Owner SUZHOU UNIV
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