文献类型：期刊文献

英文题名：An anti-miR-301a and zinc coordination driven nanozyme loaded in nanoparticle for oral therapy of inflammatory bowel disease based on colitis microenvironment regulation

作者：Zou, Jiafeng[1];Xia, Chuanhe[1];Yao, Min[1];Pan, Xier[1];Zheng, Shulei[1];Lin, Yiting[1];Zhao, Xinlin[1];Wang, Yanwen[1];Chen, Yanzuo[1,4,5];Lan, Minbo[5];Wang, Junshan[2,3];Gao, Feng[1,4,5,6]

机构：[1]East China Univ Sci & Technol, Shanghai Frontier Sci Ctr Optogenet Tech Cell Meta, Sch Pharm, Shanghai 200237, Peoples R China;[2]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai 200072, Peoples R China;[3]Bengbu First Peoples Hosp, Dept Gastroenterol, Bengbu 233000, Anhui, Peoples R China;[4]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Pharmaceut Engn & Proc Chem Engn Res Ctr, Sch Pharm, Shanghai Key Lab New Drug Design,Minist Educ, Shanghai 200237, Peoples R China;[6]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China

年份：2025

卷号：511

外文期刊名：CHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20251418172378);WOS:【SCI-EXPANDED(收录号:WOS:001462555900001)】；

基金：This work was financially supported by 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; Natural Science Foundation of Shanghai (grant 22ZR1415500) ; Research Unit of New Techniques for Live-cell Meta-bolic Imaging (Chinese Academy of Medical Sciences, grant 2019-I2M-5-013) ; Science and Technology Commission of Shanghai Chongming Municipality (grant CKY2020-05) .We thank the exceptional experimental environment of the State Key Laboratory of Bioreactor Engineering (Shanghai) , the Fundamental Research Funds for the Central Universities, the innovative research team of high-level local universities in Shanghai. We also thank Prof. Yuzheng Zhao (Y.Z., ECUST) for his help and financially support.

语种：英文

外文关键词：Coordination driven nanozyme; Anti-miR-301a; Zinc; Colitis microenvironment regulation; Inflammatory bowel disease; Oral nanoparticle

摘要：The use of miR-301a inhibitor, anti-miR-301a (anti-iR), has been widely explored for addressing inflammatory bowel disease (IBD) owing to its remarkable resistance to miR-301a, which is significantly associated with the disease course. However, the oral therapeutic outcomes of anti-iR are limited, and fail to regulate the overexpression of reactive oxygen species (ROS) and hydrogen sulfide (H2S) in the inflamed colon. In this study, based on the auxiliary advantages of zinc (Zn) coordination, we developed an anti-iR and Zn coordination-driven nanozyme (anti-iR -Zn, R-Z) to regulate ROS and H2S while promoting the transfection of anti-iR. Additionally, an oral nanoparticle (R-Z@iPS), consisting of R-Z and ROS responsive liposome, was developed to overcome the complex gastric environment, accumulating in the colonic inflamed region. In the colitis mice, R-Z@iPS could alleviate the colonic inflammation index, as well as restore the disrupted tight junctions and mucus layers by regulating ROS and H2S. Moreover, the nanoparticle downregulated the levels of miR-301a, leading to the suppression of the nuclear factor kappa-B signalling pathway, as well as increasing the expression of Smad nuclear-interacting protein 1 and B-cell translocation gene 1 to reverse colonic inflammation. R-Z@iPS could further orchestrate colitis microenvironment by increasing probiotic abundance, and decreasing harmful bacteria abundance to restore the gut microbiota. In summary, this study introduces a promising oral nanoparticle that shows agreeable safety and potential for the comprehensive clinical management of colitis, and it may alter antisense oligonucleotide treatment paradigms for other miR-301a related diseases.