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

Nat Commun. 2023 Aug 7;14(1):4746. doi: 10.1038/s41467-023-40439-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capecitabine / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Gastrointestinal Microbiome*
  • Mice
  • Nanoparticles*
  • Prebiotics

Substances

  • Prebiotics
  • Capecitabine