biostudies-literatureLi LDongguan Science and Technology of Social Development ProgramScience and Technology Program of GuangzhouNatural Science Foundation of Guangdong Province0364https://www.ebi.ac.uk/biostudies/studies/S-EPMC11077293biostudies-literatureUnknown7The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments. The antibacterial or tumor microenvironment (TME)-modulating approaches have been shown to markedly improve antitumor efficacy, strategies focused on normalizing the microbial environment are rarely reported. Here, we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects, containing hollow MnO₂ nanocarrier loaded with the chemotherapeutic drug Oxa (Oxa@HMI). On the one hand, beneficial bacteria in the colon specifically metabolized Oxa@HMI, resulting in the degradation of inulin and the generation of short-chain fatty acids (SCFAs). These SCFAs play a crucial role in modulating microbiota and stimulating immune responses. On the other hand, the hydrogel matrix underwent colon microbiota-specific degradation, enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME. In this study, we have established, for the first time, a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention. Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue, providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.Research (Washington, D.C.)Orally Administrated Hydrogel Harnessing Intratumoral Microbiome and Microbiota-Related Immune Responses for Potentiated Colorectal Cancer Treatment.PMC11077293202118009052822022010111302800652023A1515030291Wang MHe SZou ZYu MLiao BShu ZLin HZhang CLi LHu BLan XfalseOrally Administrated Hydrogel Harnessing Intratumoral Microbiome and Microbiota-Related Immune Responses for Potentiated Colorectal Cancer Treatment.The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments. The antibacterial or tumor microenvironment (TME)-modulating approaches have been shown to markedly improve antitumor efficacy, strategies focused on normalizing the microbial environment are rarely reported. Here, we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects, containing hollow MnO₂ nanocarrier loaded with the chemotherapeutic drug Oxa (Oxa@HMI). On the one hand, beneficial bacteria in the colon specifically metabolized Oxa@HMI, resulting in the degradation of inulin and the generation of short-chain fatty acids (SCFAs). These SCFAs play a crucial role in modulating microbiota and stimulating immune responses. On the other hand, the hydrogel matrix underwent colon microbiota-specific degradation, enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME. In this study, we have established, for the first time, a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention. Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue, providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.2024-01-01T00:00:00Z20242026-06-08T06:02:51.241Z2026-06-08T03:14:20.13ZS-EPMC110772933872127410.34133/research.0364