期刊
NANO LETTERS
卷 20, 期 10, 页码 7728-7736出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c03279
关键词
rheumatoid arthritis; celastrol; ROS sensitive; NF-kappa B; Notch1; macrophage
类别
资金
- National Natural Science Foundation of China [51933011, 31971296, U1904176, 81600775, 21504082]
- Zhongyuan Thousand Talents Plan Project
- Key Areas Research and Development Program of Guangdong [2019B020235001]
- Basic Science Key Project of Henan Eye Institute/Henan Eye Hospital [20JCZD002, 20JCQN001]
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 proinflammatory M1 pheno-type via regulating the NF-kappa B 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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