Preparation method and application of an oral engineering probiotic system for producing active substances in situ metabolic chemotherapy of tumors

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

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
ZHENGZHOU UNIV
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 application aims to provide a preparation method and application of an oral engineering probiotic system for producing active substances in situ metabolism of tumors. First, the probiotic is cultured, the CES gene is inserted into a plasmid as a target gene, the plasmid containing the CES gene is transfected into a probiotic competent cell by a heat shock method, the engineering probiotic capable of continuously and stably expressing carboxylesterase is obtained, and the oral engineering probiotic system is prepared by coating the engineering probiotic with a natural high molecular material, mercapto hyaluronic acid. The preparation method is scientific and reasonable, raw materials are abundant, and the preparation is easy to produce. The preparation method enhances the chemotherapy effect of colorectal cancer and reduces the toxic side effects caused by the distribution of chemotherapy drugs in other tissues and organs, provides new technical support for the treatment of colorectal cancer, is an innovation in oral microecological preparation drugs, and has great economic and social benefits.
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