Preparation methods and application of novel ortho-ester monomer and acid-sensitive polymeric gene carrier thereof

A technology of acid-sensitive polymer and gene carrier, which is applied in the direction of introducing foreign genetic material by using carrier, organic chemistry, recombinant DNA technology, etc. It can solve the problems of reducing the cycle time of the gene delivery system, reducing the efficiency of gene transfection, etc., and achieving high gene efficiency. The effects of transfection efficiency, low cytotoxicity, and good application prospects

Inactive Publication Date: 2014-02-19
ANHUI UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the cationic polymer / DNA complex is prone to non-specific adsorption with the blood components and extracellular matrix in the body, resulting in accumulation in the body and being cleared by the reticuloendothelial system, reducing the circulation time of the gene delivery system in the body and reducing gene expression. Transfection efficiency

Method used

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  • Preparation methods and application of novel ortho-ester monomer and acid-sensitive polymeric gene carrier thereof
  • Preparation methods and application of novel ortho-ester monomer and acid-sensitive polymeric gene carrier thereof
  • Preparation methods and application of novel ortho-ester monomer and acid-sensitive polymeric gene carrier thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] The synthesis method of 4-aminomethyl-2-(N,N-dimethylethoxy)-[1,3]dioxane monomer is realized through the following steps:

[0039] 1) 2,2,2-trifluoro-N-(2-(5'-N,N-dimethylethoxy)-[1,3]dioxane-4-methylene)acetamide preparation

[0040]Under nitrogen atmosphere, 11.66g (50.88mmol) 2,2,2-trifluoro-N-(2-methoxy-[1,3]dioxane-4-methylene)acetamide, 86.51mg( 0.32mmol) p-toluenesulfonic acid pyridinium salt and 13.95g (53.38mmol) 2-dimethylaminoethanol, heated to 130 ° C for 2 hours, cooled to room temperature, and obtained 25.63 g of the initial product of light yellow solid, no need for purification , which can be directly used in the next reaction.

[0041] 2) Preparation of 4-aminomethyl-2-(N,N-dimethylethoxy)-[1,3]dioxane

[0042] 25.63 g of 2,2,2-trifluoro-N-(2-(5'-N,N-dimethylethoxy)-[1,3]dioxane-4-methylene)ethane The crude product of the amide monomer was dissolved in 235ml of tetrahydrofuran, stirred and dissolved, and then 235ml of 2.0M sodium hydroxide solution...

Embodiment 2

[0044] The synthesis method of 4-aminomethyl-2-(N,N-dimethylethoxy)-[1,3]dioxane monomer is realized through the following steps:

[0045] 1) 2,2,2-trifluoro-N-(2-(5'-N,N-dimethylethoxy)-[1,3]dioxane-4-methylene)acetamide preparation

[0046] Under nitrogen atmosphere, 10.60g (46.26mmol) 2,2,2-trifluoro-N-(2-methoxy-[1,3]dioxane-4-methylene)acetamide, 78.66mg( 0.29mmol) pyridinium p-toluenesulfonate and 12.68g (48.54mmol) 2-dimethylaminoethanol, heated to 130°C for 2 hours, cooled to room temperature to obtain 23.29g of the initial product as a light yellow solid, no need for purification , which can be directly used in the next reaction.

[0047] 2) Preparation of 4-aminomethyl-2-(N,N-dimethylethoxy)-[1,3]dioxane

[0048] 23.29 g containing 2,2,2-trifluoro-N-(2-(5'-N,N-dimethylethoxy)-[1,3]dioxane-4-methylene)ethane The crude product of the amide monomer was dissolved in 213ml of tetrahydrofuran, stirred and dissolved and then added with 213ml of 2.0M sodium hydroxide sol...

Embodiment 3

[0050] Accurately weigh 1.00g (5.46mmol) N-succinimide methacrylate, 0.328g (0.06mmol) macromolecular chain transfer agent, and 1.99mg (0.01mmol) initiator in a clean and dry glass reaction bottle , and finally add 2.5 ml of N,N-dimethylformamide from which water has been removed. Introduce nitrogen gas into the polymer, seal the tube by bubbling continuously for more than 30 minutes, and then put the reaction bottle into an oil bath at 70°C for polymerization. After reacting for 2 hours, dissolve the obtained primary product in N,N-dimethyl In formamide, after shaking and dissolving completely, the polymer was precipitated with a large amount of ether and filtered. The sedimentation was repeated twice, and finally the obtained polymer was vacuum-dried to constant weight. Under nitrogen protection, 0.3g (0.032mmol) of the obtained copolymer, 0.40g (2.10mmol) of the new orthoester monomer 4-aminomethyl-2-(N,N-dimethylethoxy)-[1 ,3] Dioxane was accurately weighed and put into ...

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Abstract

The invention discloses preparation methods and application of a novel ortho-ester monomer and an acid-sensitive polymeric gene carrier thereof. A polymer carrier transmission system prepared by the methods has controllable acid degradation rate, relatively low cytotoxicity and relatively high gene transfection efficiency and is a non-viral polymeric gene carrier which has a good application prospect.

Description

technical field [0001] The invention discloses a preparation method and technology of a novel high-efficiency non-viral gene carrier system, belonging to the field of gene therapy. Background technique [0002] Gene therapy is a method of introducing exogenous genes into target cells and effectively expressing them to achieve therapeutic purposes. An excellent gene delivery system must be able to encapsulate and protect nucleic acid substances, avoid degradation of endosomes, and be able to specifically target the target organs of the body. Vector research and development has always been one of the core technologies in the field of gene therapy research. Gene vectors can be divided into two categories: viral vectors and non-viral vectors. The transfection efficiency of non-viral gene vectors is significantly lower than that of viral vectors, mainly because non-viral vectors have to go through many obstacles such as cell membrane uptake, endosome escape, intracytoplasmic tra...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D317/34C08F120/36C08F2/38C08F8/00C12N15/85
CPCC07D317/34C08F8/32C08F293/005C08F2438/03C12N15/85
Inventor 唐汝培赖俊平
Owner ANHUI UNIVERSITY
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