Preparation method of targeting folic acid-hydrophobic anticancer drug hydrogel

Abstract

The invention relates to a preparation method of small molecular hydrogel precursor molecules based on folic acid-anticancer drugs. The obtained compound is prepared into small molecular hydrogel by reducing disulfide bonds using reducing agents (glutathione and dithiothreitol). Specifically, the preparation method comprises the following steps of: firstly, synthesizing folic acid connected small peptides by a solid phase synthesis method, then derivatizing an anticancer drug (taxol, camptothecin, hydroxycamptothecine and the like) by butanedioic anhydride or glutaric anhydride to remove one carboxyl group, and connecting the folic acid connected small peptides with the derivatized anticancer drug. The precursor molecules not only have a targeting effect, but also have good solubility and are capable of self assembling into small molecular hydrogel by reduction of the disulfide bonds. The novel transmission system of the hydrophobic anticancer drug established by the invention not only greatly improves the solubility of the hydrophobic anticancer drug in water, but also is capable of targeting tumor tissues, thus reducing toxic side effects.

Description

technical field [0001] The technical solution of the present invention relates to a class of small molecule hydrogel precursor molecules based on folic acid and anticancer drugs, and the precursor molecules form a stable injectable small molecule under reducing agent (glutathione or dithiothreitol) conditions. Molecular hydrogel approach Background technique [0002] In 1963, American chemists Varney and Wall discovered that the bold substance of the western yew trunk had anti-tumor activity, but it was not until 1971 that they cooperated with Professor McFarr of Duke University to determine the structure of its active ingredient and named it for paclitaxel. This drug entered clinical research in 1983 and entered the Chinese market in 1994. It is a new anticancer drug, but it is very hydrophobic, so its clinical application is limited, that is, some co-solvents are often needed to dissolve it for administration. However, these co-solvents, such as polyoxyethylene castor o...

AI Technical Summary

Problems solved by technology

So far, there have been no reports of using polypeptides to link hydrophobic anticancer drugs and then induce their self-assembly to form small molecule hydrogels through disulfide bond reduction.

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