Method for synthesizing branched molecular gene carrier with the pentaerythritol derivative as core

Abstract

The invention relates to the preparation technology of dendrite macromolecule gene carrier, in particular, the dendrite macromolecule whose number of active groups is three times that of the old nuclear product is synthesized by designing a new nuclear molecule. The technical scheme is to use trihydroxymethylaminomethane to form a new nuclear molecule pentaerythritol-dodecylamine with pentaerythritol-quaternary acid chloride derivatives after a simple organic reaction. Compared with the products of old nuclear generations, the surface charge density and the number of active amine end groups of the new generation of polymers synthesized by the new nuclei are three times higher, which is conducive to obtaining higher gene transfer efficiency. The surface of this kind of polymer is rich in amine groups, which can combine with negatively charged DNA to form a nano-supramolecular complex, which can be used as a gene carrier to transfer plasmid DNA into cells. Cell transfection experiments show that its efficiency is equivalent to that of commonly used liposome gene transfer reagents, but its cytotoxicity is far less than that of the latter. Good application prospects.

Description

technical field [0001] The present invention relates to the preparation technology of dendrimer nano-gene carrier, in particular, it utilizes pentaerythritol derivatives to react with tris-hydroxymethylaminomethane (Tris)-tribasic ester derivatives to generate new nuclear molecules, and then synthesizes Each generation of dendrimers has three times the number of active groups of the previous generations of dendrimers, so that the low-generation products can have the surface charge density and the number of active functional groups of the previous higher-generation products. The dendrimer nanometer gene carrier produced by the invention can be used for gene transfer and treatment of cancer, cardiovascular disease and the like. Background technique [0002] In the in-depth study of gene therapy in recent years, it has been found that many genes have significant curative effects on tumors, cardiovascular diseases, diabetes and so on. However, since the fatal accident in clinic...

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Problems solved by technology

[0005] However, as the molecular weight increases in the synthesis of dendrimers, the separation and purification of each generation of samples becomes more and more difficult, because with the increase of the number of surface functional groups, its intramolecular and intermolecular hydrogen bonds and van der Waals interactions The force will be greatly increased, which will make it more difficult to extract the remaining reaction raw materials, and the effect of the subsequent reaction will be reduced, which will affect the percentage of grafting in the next step, resulting in irregular molecular structure and formation of defects.