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Synergistic rheumatoid arthritis therapy by interrupting the detrimental feedback loop to orchestrate hypoxia M1 macrophage polarization using an enzyme-catalyzed nanoplatform

Authors :
Dong Guo
Hui Liu
Sheng Zhao
Xinya Lu
Haoyu Wan
Yitao Zhao
Xinzhi Liang
Anbiao Zhang
Mengyuan Wu
Zhisheng Xiao
Ning Hu
Zhong Li
Denghui Xie
Source :
Bioactive Materials, Vol 41, Iss , Pp 221-238 (2024)
Publication Year :
2024
Publisher :
KeAi Communications Co., Ltd., 2024.

Abstract

A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders.

Details

Language :
English
ISSN :
2452199X
Volume :
41
Issue :
221-238
Database :
Directory of Open Access Journals
Journal :
Bioactive Materials
Publication Type :
Academic Journal
Accession number :
edsdoj.b86d20752f3c406f96bd7014d76e9d70
Document Type :
article
Full Text :
https://doi.org/10.1016/j.bioactmat.2024.07.026