Inflammation-Targeted Celastrol Nanodrug Attenuates Collagen-Induced Arthritis through NF-κB and Notch1 Pathways

• DOI: 10.1021/acs.nanolett.0c03279
• Publication Date: 2020-09-23T15:39:49Z
• Authors: Lemei An; Zhanrong Li; Liuqi Shi; Liujun Wang; Yong Wang; Lin Jin; Xintao Shuai; Jingguo Li
• Keywords: Celastrol

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, frequent parenteral delivery poor water solubility of Cel restrict its further therapeutic applications. Here, aiming at effectively overcoming short half-life boost beneficial effects for treating RA, we developed polymeric micelle based on reactive oxygen species (ROS) sensitive polymer. Our results demonstrated that may inhibit repolarization macrophages toward pro-inflammatory M1 pheno-type via regulating NF-κB Notch1 pathways, resulted in significantly decreased secretion multiple cytokines suppress RA progression. Consequently, Cel-loaded alleviated major RA-associated symptoms including articular scores, ankle thickness, synovial inflammation, erosion, degradation.