文献类型：期刊文献

英文题名：Tofacitinib Citrate Coordination-Based Dual-Responsive/Scavenge Nanoplatform Toward Regulate Colonic Inflammatory Microenvironment for Relieving Colitis

作者：Zou, Jiafeng[1];Jiang, Kun[1];Chen, You[1];Ma, Ying[1];Xia, Chuanhe[1];Ding, Wenxing[1];Yao, Min[1];Lin, Yiting[1];Chen, Yanzuo[1];Zhao, Yuzheng[1,2,3,4];Gao, Feng[1,2,4,5,6]

机构：[1]East China Univ Sci & Technol, Shanghai Frontier Sci Ctr Optogenet Tech Cell Meta, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Chinese Acad Med Sci, Res Unit New Tech Live cell Metab Imaging, Beijing 100050, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[6]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Shanghai 200237, Peoples R China

年份：2024

卷号：13

期号：30

外文期刊名：ADVANCED HEALTHCARE MATERIALS

收录：;EI(收录号：20243516928059);WOS:【SCI-EXPANDED(收录号:WOS:001296574500001)】；

基金：This work was financially supported by the Development Program of China (grant 2019YFA0904800 to Y.Z.); National Natural Science Foundation of China (grant 32150030, 32030065, 32121005, and 92049304 to Y.Z.); Science and Technology Commission of Shanghai Municipality (grant 10DZ2220500 to F.G.); Shanghai Committee of Science and Technology (grant 11DZ2260600 to F.G.); Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (to Y.Z.). Research Unit of New Techniques for Live-cell Metabolic Imaging (Chinese Academy of Medical Sciences, grant 2019-I2M-5-013 to Y.Z.); Postdoctoral Fellowship Program of CPSF (grant GZC20230805 to K.J.). 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 Innovative research team of high-level local universities in Shanghai. The author also thanks Prof. Xianjun Chen, Prof. Minbo Lan, and Prof. Yun Tang (ECUST) for their help and comments.

语种：英文

外文关键词：colitis; colonic inflammatory microenvironment; coordination nanoplatform; dual-responsive; dual-scavenge; tofacitinib citrate

摘要：Ulcerative colitis is an inflammation of the colon characterized by immune dysregulation and intestinal inflammation. Developing safe oral nanomedicines that suppress intestinal inflammation, while modulating colonic inflammatory microenvironment by scavenging reactive oxygen species (ROS) and hydrogen sulfide (H2S) is crucial for the effective treatment of colitis. Here, the tofacitinib citrate and copper coordination-based nanoparticle (TF-Cu nanoparticle, T-C) to dual-scavenge ROS and H2S by coordination competition is synthesized. Moreover, the coordination of T-C using computer simulation is explored. To enhance the acid stability and inflammatory targeting of T-C, it is encapsulated with hyaluronic acid-modified chitosan, along with a calcium pectinate coating (T-C@HP). Owing to the dual pH/pectinase-responsive characteristics of T-C@HP, the nanoplatform can target inflamed colonic lesions, inhibiting phosphorylated Janus kinase 1. Furthermore, T-C@HP scavenges ROS and H2S, as well as increases NADPH levels, which is investigated by combining biosensor (HyPer7 and iNap1/c) and chemical probes. T-C@HP also alleviates colitis by regulating the colonic inflammatory microenvironment through multiple processes, including the modulation of apoptosis, macrophage polarization, tight junction, mucus layer, and intestinal flora. Complemented by satisfactory anti-inflammatory and biosafety results, this nanoplatform represents a promising, effective, and safe treatment option for colitis patients. Here, a tofacitinib citrate and copper coordination-based of dual pH/pectinase-responsive nanoplatform (T-C@HP) is introduced to dual scavenge hydrogen sulfide and reactive oxygen species, regulate apoptosis, phosphorylated Janus kinase 1 expression, macrophage polarization, tight junction, mucus layer, and intestinal flora. This nanoplatform presents a novel and safety approach for ulcerative colitis targeted therapy. image