Citation: Ruifeng Liang, Yanbei Tu, Peng Hua, Yongzhuo Huang, Meiwan Chen. ROS-responsive micelles co-loaded dexamethasone and pristimerin to restore the homeostasis of the inflammatory microenvironment for rheumatoid arthritis therapy[J]. Chinese Chemical Letters, ;2025, 36(6): 110335. doi: 10.1016/j.cclet.2024.110335 shu

ROS-responsive micelles co-loaded dexamethasone and pristimerin to restore the homeostasis of the inflammatory microenvironment for rheumatoid arthritis therapy

Ruifeng Liang ^{a, 1} ,
Yanbei Tu ^{a, 1} ,
Peng Hua ^a ,
Yongzhuo Huang ^b ,
Meiwan Chen ^{a, *,}

a.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
b.
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528437, China

mwchen@um.edu.mo

Received Date: 27 February 2024
Revised Date: 7 August 2024
Accepted Date: 11 August 2024
Available Online: 12 August 2024

Figures(6)

Invasive fibroblast-like synoviocytes (FLS), inflammatory macrophages and osteoclasts are the main three contributors to rheumatoid arthritis (RA) progression by promoting synovial inflammation and destructing cartilage and bone. Targeting these three cell types for restoring the inflammatory homeostasis microenvironment may be a promising anti-RA strategy. Herein, we prepared a reactive oxygen species (ROS)-responsive micelles (DPTM) to co-load dexamethasone (DEX) and pristimerin (PRI) for RA therapy. This ROS-responsive system exhibits the following advantages: (1) It makes use of the "ELVIS" effect for passive delivery and targeting the ROS environment of RA-related cells to rapidly release the payload drugs DEX and PRI. (2) Compared with free drugs, DPTM showed stronger effect on the inhibition of RA-FLS proliferation and the promotion of RA-FLS apoptosis. Moreover, DPTM could significantly weaken the migration ability of RA-FLS as indicated by the results of wound healing assay and transwell assay. (3) DPTM exerted stronger cellular uptake and anti-inflammatory effect in M1 macrophages. (4) In the model studying receptor activator of nuclear factor kappa-B ligand (RANKL)-induced differentiation of bone marrow-derived macrophages (BMDMs) to osteoclasts, DPTM showed a stronger inhibitory activity on osteoclast formation as compared to free drugs. Taken together, these results highlighted the potential of DPTM for targeted RA therapy via inhibition of RA-FLS abnormal activation, macrophage polarization and osteoclastogenesis.
- Rheumatoid arthritis,
- Micelles,
- Macrophages,
- Fibroblast-like synoviocytes,
- Osteoclastogenesis
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