Inflammation responsive tofacitinib loaded albumin nanomedicine for targeted synergistic therapy in ulcerative colitis  

作　　者：Bang Li Xiaoyan Liu Qi Long Xiaoduan Zhuang Yanfei Gao Barkat Ali Haoting Chen Dongyang Zhang Xinying Wang Weisheng Guo 

机构地区：[1]Department of Gastroenterology,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China [2]Department of Minimally Invasive Interventional Radiology,the State Key Laboratory of Respiratory Disease,School of Biomedical Engineering&The Second Affiliated Hospital,Guangzhou Medical University,Guangzhou 510260,China

出　　处：《Nano Research》2023年第7期9873-9884,共12页纳米研究（英文版）

基　　金：This work was partially supported by grants from the National Natural Science Foundation of China(Nos.31971302 and 82170532);the Natural Science Foundation of Guangdong Province of China(No.2019A1515011597);the talent young scientist supporting program of China Association for Science and Technology,the Educational Commission of Guangdong Province of China key Project(No.2020ZDZX2001);the joint grant between Guangzhou City and College(No.202102010106);Guangzhou Science and Technology Plan Project(No.202201011509).

摘　　要：Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting systemic side effects including infections,cancers and lymphoma limit its popularity of clinical application.This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1(anti-MAdCAM-1)antibody modified reactive oxygen species(ROS)responsive human serum albumin-based nanomedicine denoted as THM,to improve the therapeutic efficacy of tofacitinib for UC treatment.THM has the drug releasing properties in response to ROS stimulation.In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages.Meanwhile,the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing.In addition,in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon.Moreover,THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis.This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.

关 键 词：ulcerative colitis mucosal vascular addressin cell-adhesion molecule-1(MAdCAM-1) tofacitinib reactive oxygen species(ROS)-responsive targeted delivery 

分 类 号：R574.62[医药卫生—消化系统]