MEDICINE AND HEALTH

The study found a new strategy of integrated chemotherapy-intestinal microbiota regulation against colorectal cancer


Colorectal cancer (CRC) has a high incidence and mortality rate, threatening human life and health. As a first-line agent for the treatment of metastatic CRC, the chemotherapy drug capecitabine (Cap) has advantages such as tumor-specific toxicity and high response rate, but its plasma half-life is extremely short and requires high doses twice daily, resulting in dose-related toxicity. Therefore, the development of delivery systems that can effectively delay their plasma clearance is critical to improving the clinical efficacy of Cap.

The occurrence and development of CRC is closely related to the intestinal microbiota, some probiotics have been reported to enhance the host anti-tumor immune response, and some harmful bacteria are related to CRC progression and treatment resistance. Prebiotics represented by xylan can be digested and metabolized by probiotics, increase the proportion of beneficial bacteria in the intestine, and have good biocompatibility, making them have the potential to become a carrier material for chemotherapy drugs.

On August 7, Li Yaping’s research group of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, published a report entitled Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves Research paper on colorectal cancer therapy.

The study synthesized an amphiphilic xylan-stearic acid conjugate (Sxy). Sxy can self-assemble to form nanoparticles in water, and stearic acid-modified Cap is wrapped in the nanoparticle core to obtain Cap-loaded prebiotic nanoparticle SCXN. Studies have shown that after oral administration, SCXN is stable in the stomach, under the action of specific bacteria in the intestine, xylan is gradually degraded, nanoparticles dissociate and continuously release Cap, compared with free drugs, it can slow down the absorption of Cap by the small intestine into blood circulation, slow down clearance, increase tumor accumulation, and improve tumor cell killing efficiency. At the same time, the degradation of xylan increased the proportion of intestinal probiotics, reduced the proportion of carcinogenic bacteria, and increased the content of beneficial metabolite short-chain fatty acids. The efficacy evaluation results of CT26 and MC38 colon cancer mouse models showed that compared with free Cap, SCXN increased the number of intratumoral CD8+ T cells, reduced the number of regulatory T cells, enhanced the anti-tumor immune response, and the tumor suppression rate increased from 5.29% to 71.78%. In addition, SCXN has good biocompatibility, which can extend the median survival of colon cancer model mice from 14 days to 33.5 days. This prebiotic-based integrated intestinal microbiota regulation-chemotherapy nanodelivery system is expected to provide a new strategy for CRC treatment.

The research work was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province and the “Yangfan Program” of Shanghai. The National Protein Science Research (Shanghai) Facilities of Zhangjiang Laboratory and the Cryo-EM Research Center of Shanghai Institute of Materia Medica-Callia supported this research in the experiment. (Source: Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

Related paper information:https://doi.org/10.1038/s41467-023-40439-y

SCXN fights colorectal cancer through intestinal flora regulation and chemotherapy in combination

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