Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy

Tianqun Lang, Runqi Zhu, Xiao Zhu, Wenlu Yan, Yu Li, Yihui Zhai, Ting Wu, Xin Huang, Qi Yin () and Yaping Li ()
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Tianqun Lang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Runqi Zhu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Xiao Zhu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Wenlu Yan: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Yu Li: Nanjing University of Chinese Medicine
Yihui Zhai: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Ting Wu: Nanjing Medical University
Xin Huang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Qi Yin: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Yaping Li: Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Colorectal cancer (CRC) therapy efficiency can be influenced by the microbiota in the gastrointestinal tract. Compared with traditional intervention, prebiotics delivery into the gut is a more controllable method for gut microbiota modulatory therapy. Capecitabine (Cap), the first-line chemotherapeutic agent for CRC, lacks a carrier that can prolong its half-life. Here, we construct a Cap-loaded nanoparticle using the prebiotic xylan-stearic acid conjugate (SCXN). The oral administration of SCXN delays the drug clearance in the blood and increases the intra-tumoral Cap concentration in the CRC mouse model. SCXN also facilitates the probiotic proliferation and short chain fatty acid production. Compared with free Cap, SCXN enhances the anti-tumor immunity and increases the tumor inhibition rate from 5.29 to 71.78%. SCXN exhibits good biocompatibility and prolongs the median survival time of CRC mice from 14 to 33.5 d. This prebiotics-based nanoparticle provides a promising CRC treatment by combining gut microbiota modulation and chemotherapy.

Date: 2023
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DOI: 10.1038/s41467-023-40439-y

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