Preparation method and application of oral engineering probiotic system for generating active substances through tumor in-situ metabolic chemotherapy

By genetically engineering the probiotic Escherichia coli Nissle 1917 to express carboxylesterase and encapsulating it with thiolated hyaluronic acid, irinotecan was converted in situ to SN-38 in the intestinal segment of colorectal cancer. This solved the problems of low drug accumulation and toxic side effects of irinotecan in the treatment of colorectal cancer, enhanced the chemotherapy effect and reduced the side effects.

CN122398867APending Publication Date: 2026-07-17ZHENGZHOU UNIV
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Patent Information

Application Number
CN202610560850.X
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-04-27
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

Irinotecan has a low accumulation of drug at the tumor site in the treatment of colorectal cancer, resulting in poor chemotherapy efficacy, and its systemic distribution causes serious toxic side effects, which current technologies have not been able to effectively solve.

Method used

By genetically engineering the probiotic Escherichia coli Nissle 1917 to express carboxylesterase, and using thiolated hyaluronic acid to encapsulate the engineered probiotic, targeted colonization of tumor sites can be achieved. Furthermore, irinotecan is converted into the active metabolite SN-38 in situ in the colorectal cancer intestinal segment, enhancing the effect of chemotherapy and avoiding loss during the liver activation process.

Benefits of technology

It increased the accumulation of SN-38 at the tumor site, enhanced the efficacy of chemotherapy for colorectal cancer, reduced the toxic side effects of chemotherapy drugs in other tissues and organs, regulated the balance of intestinal microbiota, and reduced adverse reactions.

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Abstract

The invention aims to provide a preparation method and application of an oral engineering probiotic system for generating active substances through tumor in-situ metabolism chemotherapy, and the preparation method comprises the following steps: firstly, culturing probiotics, inserting CES genes as target genes into plasmids, transfecting the plasmids containing the CES genes into probiotic competent cells through a heat shock method, and carrying out freeze drying to obtain the oral engineering probiotic system for generating active substances through tumor in-situ metabolism chemotherapy. The engineering probiotics capable of continuously and stably expressing carboxylesterase are obtained, and an oral engineering probiotic system is prepared by coating the engineering probiotics with a natural polymer material sulfhydrylated hyaluronic acid. The preparation method is scientific and reasonable, raw materials are rich, production and preparation are easy, the colorectal cancer chemotherapy effect is enhanced, toxic and side effects caused by distribution of chemotherapy drugs in other tissues and organs are reduced, a new technical support is provided for treatment of colorectal cancer, and the oral microecological preparation is an innovation of oral microecological preparation drugs and has huge economic and social benefits.
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