Tofacitinib Citrate Coordination-Based Dual-Responsive/Scavenge Nanoplatform Toward Regulate Colonic Inflammatory Microenvironment for Relieving Colitis.

Autor: Zou J; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Jiang K; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Chen Y; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Ma Y; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Xia C; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Ding W; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Yao M; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Lin Y; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Chen Y; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Zhao Y; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.; Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.; Research Unit of New Techniques for Live-cell Metabolic Imaging, Chinese Academy of Medical Sciences, Beijing, 100050, China.; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China., Gao F; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.; Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.; Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, 200237, China.; Engineering Research Center of Pharmaceutical Process Chemistry, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Dec; Vol. 13 (30), pp. e2401869. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1002/adhm.202401869
Abstrakt: 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 (H 2 S) 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 H 2 S 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 H 2 S, 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.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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