Orally Administrated Hydrogel Harnessing Intratumoral Microbiome and Microbiota-Related Immune Responses for Potentiated Colorectal Cancer Treatment

• Published in: Research (Washington) 2024-01, Vol.7, p.0364
• Main Authors: Li, Lei, He, Shouhua, Liao, Boyi, Wang, Manchun, Lin, Huimin, Hu, Ben, Lan, Xinyue, Shu, Zhilin, Zhang, Chao, Yu, Meng, Zou, Zhaowei
• Format: Article
• Language: English
• ISSN: 2639-5274; 2639-5274
• DOI: 10.34133/research.0364

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 MnO 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.