雷公藤醇
炎症
类风湿性关节炎
癌症研究
NF-κB
化学
药理学
软骨
关节炎
医学
细胞凋亡
免疫学
生物化学
解剖
作者
Lemei An,Zhanrong Li,Liuqi Shi,Liujun Wang,Yong Wang,Lin Jin,Xintao Shuai,Jingguo Li
出处
期刊:Nano Letters
[American Chemical Society]
日期:2020-09-23
卷期号:20 (10): 7728-7736
被引量:133
标识
DOI:10.1021/acs.nanolett.0c03279
摘要
Rheumatoid arthritis (RA) is a systemic inflammatory disorder which can cause bone and cartilage damage leading to disability, yet the treatment remains unsatisfactory nowadays. Celastrol (Cel) has shown antirheumatic activity against RA. However, the frequent parenteral delivery and poor water solubility of Cel restrict its further therapeutic applications. Here, aiming at effectively overcoming the poor water solubility and short half-life of Cel to boost its beneficial effects for treating RA, we developed a polymeric micelle for Cel delivery based on a reactive oxygen species (ROS) sensitive polymer. Our results demonstrated that Cel may inhibit the repolarization of macrophages toward the pro-inflammatory M1 pheno-type via regulating the NF-κB and Notch1 pathways, which resulted in significantly decreased secretion of multiple pro-inflammatory cytokines to suppress the RA progression. Consequently, the Cel-loaded micelle effectively alleviated the major RA-associated symptoms including articular scores, ankle thickness, synovial inflammation, bone erosion, and cartilage degradation.
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