文献类型：期刊文献

英文题名：Oral cerium-based nanoplatform conjugated with gold to load anti-miR-301a for pH-transited multi-modal therapy of inflammatory bowel disease

作者：Zou, Jiafeng[1,2];Ji, Qingdong[1];Pan, Xier[1];Lin, Yiting[1];Zhao, Xinlin[1];Chen, Xinyi[1];Yang, Liping[1];Lu, Jing[1];Zheng, Shuhui[1];Zhang, Zhuo[1,3];Jiang, Kun[1,3];Gao, Feng[1,2,3,4]

机构：[1]East China Univ Sci & Technol, Shanghai Frontier Sci Ctr Optogenet Tech Cell Meta, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Pharmaceut Engn & Proc Chem Engn Res Ctr, Shanghai Key Lab New Drug Design, Sch Pharm,Minist Educ, Shanghai 200237, Peoples R China

年份：2026

卷号：529

外文期刊名：CHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20260319936300);WOS:【SCI-EXPANDED(收录号:WOS:001675032600001)】；

基金：This work was financially supported by the Development Program of China (grant 2019YFA0904800) , National Natural Science Foundation of China (grant 32150030, 32030065, 32121005 and 92049304) , Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Research Unit of New Techniques for Live-cell Metabolic Imaging (Chinese Academy of Medical Sciences, grant 2019-I2M-5-013) , Postdoctoral Fellowship Program of CPSF (grant GZC20230805) , and Shanghai Rising-Star Program (grant 24YF2708900) . The author thanks the exceptional experimental environment of the State Key Laboratory of Bioreactor Engineering (Shanghai) , the Fundamental Research Funds for the Central Universities. The authors also thank Prof. Yuzheng Zhao, Prof. Xianjun Chen, and Prof. Minbo Lan from East China University of Science and Technology (ECUST) for their help.

语种：英文

外文关键词：Oral nanoplatform; Anti-miR-301a; pH-transited multi-modal therapy; Inflammatory bowel disease; Cerium-based nanozyme; Anti-fibrosis

摘要：Inflammatory bowel disease (IBD) and its associated fibrosis, given the evolving inflammatory colonic micro-environment and multi-pathogenic mechanisms, often pose significant challenges to current treatment regimens. Herein, we innovatively developed the gold (Au)-conjugated cerium oxide nanozyme to load anti-miR-301a (R-CA), arming with the lignin (R-CAL) to acquire a pH-responsive nanoplatform with the oral acid-resistant and inflammatory colonic accumulation properties. R-CA escaped from lysosomes by alkalization effects, following liberation from R-CAL within the inflamed colon, exerting the antisense oligonucleotide (ASO) therapy, and pH-transited therapy. Specifically, the oral nanoplatform downregulated miR-301a to modulate the SMAD4/ pSTAT3/NF-kappa B signaling pathway, promoting the M2 macrophage polarization in chronic colitis mice. Furthermore, R-CAL reduced the lactate to restore the metabolic function and prevent the fibrosis in the process of pH elevation. Moreover, R-CAL regulated the reactive oxygen species/reactive nitrogen species (ROS/RNS) and NADPH levels, further inhibiting pSTAT3 expression and reinforcing the cell crosstalk to repair the colonic barrier. Additionally, the M2 macrophage reinforced the probiotics while dispersing Th17 cells to enhance the colonic homeostasis regulation therapy of R-CAL, resisting the inflammation and fibrosis eventually. This oral nanoplatform with the pH-transited multi-modal therapy and great biocompatibility pioneers an ASO treatment paradigm for the clinical management of IBD and its associated fibrosis.