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

作　　者：Lei Li Shouhua He Boyi Liao Manchun Wang Huimin Lin Ben Hu Xinyue Lan Zhilin Shu Chao Zhang Meng Yu Zhaowei Zou 

机构地区：[1]Department of General Surgery,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China [2]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong Provincial Key Laboratory of New Drug Screening and Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China

出　　处：《Research》2025年第1期68-88,共21页研究(英文)

基　　金：supported by the Natural Science Foundation of Guangdong Province(2023A1515030291);Science and Technology Program of Guangzhou(202201011130280065);Dongguan Science and Technology of Social Development Program(20211800905282).

摘　　要：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^(2) 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.

关 键 词：intratumoral microbiota antitumor treatmentsthe intestinal microbiota normalizing microbial environment colorectal cancer treatment HYDROGEL microbiota related immune responses 

分 类 号：R730.5[医药卫生—肿瘤] R73[医药卫生—临床医学]