ROS-Responsive Berberine Polymeric Micelles Effectively Suppressed the Inflammation of Rheumatoid Arthritis by Targeting Mitochondria

作     者：Xing-xing Fan Meng-ze Xu Elaine Lai-Han Leung Cai Jun Zhen Yuan Liang Liu Xing-xing Fan;Meng-ze Xu;Elaine Lai-Han Leung;Cai Jun;Zhen Yuan;Liang Liu

作者机构：State Key Laboratory of Quality Research in Chinese MedicineMacao Institute For Applied Research in Medicine and HealthMacao University of Science and TechnologyAvenida Wai LongTaipaMacao SARChina Faculty of Health SciencesUniversity of MacaoTaipaMacao SARChina 

出 版 物：《Nano-Micro Letters》 (纳微快报（英文版）)

年 卷 期：2020年第12卷第6期

页      面：138-151页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：FDCT grants from the Science and Technology Development Fund of Macao(Project Code:003/2018/A1 Grant to FXX 0011/2018/A1 and 025/2015/A1 Grants to YZ) 

主　　题：Rheumatoid arthritis Reactive oxygen species Nanoparticles Berberine Oxygen consumption rate 

摘      要：Rheumatoid arthritis(RA)is an autoimmune disease,which attacks human joint system and causes lifelong inflammatory *** date,no cure is available for RA and even the ratio of achieving remission is very ***,to enhance the efficacy of RA treatment,it is essential to develop novel approaches specifically targeting pathological *** this study,we discovered that RA synovial fibroblasts exhibited higher reactive oxygen species(ROS)and mitochondrial superoxide level,which were adopted to develop ROS-responsive nano-medicines in inflammatory microenvironment for enhanced RA treatment.A selenocystamine-based polymer was synthesized as a ROS-responsive carrier nanoplatform,and berberine serves as a tool *** assembling,ROS-responsive berberine polymeric micelles were fabricated,which remarkably increased the uptake of berberine in RA fibroblast and improved in vitro and in vivo efficacy ten times ***,the anti-RA effect of micelles was blocked by the co-treatment of AMPK inhibitor or palmitic acid,indicating that the mechanism of micelles was carried out through targeting mitochondrial,suppressing lipogenesis and finally inhibiting cellular *** together,our ROS-responsive nano-medicines represent an effective way of preferentially releasing prodrug at the inflammatory microenvironment and improving RA therapeutic efficacy.