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

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. Gut microbiota regulates colorectal cancer (CRC) progression and respond to therapy. Here the authors generate nanoparticles using prebiotic micelles and loaded with the chemo drug capecitabine that boost gastrointestinal probiotic response, increase anti-tumour immunity and improve survival when provided orally in CRC preclinical murine models.

Automated summary

Gut microbiota plays a significant role in colorectal cancer (CRC) therapy. Researchers have developed nanoparticles loaded with the chemotherapy drug capecitabine, which are made from prebiotic micelles. These nanoparticles enhance the probiotic response, increase anti-tumour immunity, and improve survival in CRC preclinical murine models when administered orally. This prebiotics-based nanoparticle shows promise as a combination therapy for CRC by modulating gut microbiota and providing chemotherapy.