Rosmarinic acid nanomedicine for rheumatoid arthritis therapy: Targeted RONS scavenging and macrophage repolarization

Beilei Lu; Cuixian Li; Luxia Jing; Fan Zhuang; Huijing Xiang; Yu Chen; Beijian Huang

doi:10.1016/j.jconrel.2023.09.012

Rosmarinic acid nanomedicine for rheumatoid arthritis therapy: Targeted RONS scavenging and macrophage repolarization

J Control Release. 2023 Oct:362:631-646. doi: 10.1016/j.jconrel.2023.09.012. Epub 2023 Sep 17.

Authors

Beilei Lu¹, Cuixian Li¹, Luxia Jing¹, Fan Zhuang¹, Huijing Xiang², Yu Chen³, Beijian Huang⁴

Affiliations

¹ Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Medical Imaging, Shanghai 200032, PR China; Institute of Medical Ultrasound and Engineering, Fudan University, Shanghai 200032, PR China.
² Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, PR China. Electronic address: xianghuijing@shu.edu.cn.
³ Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, PR China. Electronic address: chenyuedu@shu.edu.cn.
⁴ Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Medical Imaging, Shanghai 200032, PR China; Institute of Medical Ultrasound and Engineering, Fudan University, Shanghai 200032, PR China. Electronic address: huang.beijian@zs-hospital.sh.cn.

PMID: 37708976
DOI: 10.1016/j.jconrel.2023.09.012

Abstract

The infiltration of inflammatory cells, especially macrophages, integrated with the production of reactive oxygen and nitrogen species (RONS) and the release of inflammatory cytokines play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Synergistic combination of RONS scavenging and macrophage repolarization from pro-inflammatory M1 phenotype towards anti-inflammatory M2 phenotype, provides a promising strategy for efficient RA treatment. Herein, this study reported a unique self-assembly strategy to construct distinct rosmarinic acid nanoparticles (RNPs) for efficient RA treatment using the naturally occurring polyphenol-based compound, rosmarinic acid (RosA). The designed RNPs exhibited favorable capability in scavenging RONS and pro-inflammatory cytokines produced by macrophages. Attributing to the widened vascular endothelial-cell gap at inflammation sites, RNPs could target and accumulate at the inflammatory joints of collagen-induced arthritis (CIA) rats for guaranteeing therapeutic effect. In vivo investigation demonstrated that RNPs alleviated the symptoms of RA, including joint swelling, synovial hyperplasia, cartilage degradation, and bone erosion in CIA rats. Additionally, the designed RNPs promoted macrophage polarization from M1 phenotype towards M2 phenotype, resulting in the suppressed progression of RA. Therefore, this research represents the representative paradigm for RA therapy using antioxidative nanomedicine deriving from the natural polyphenol-based compound.

Keywords: Antioxidant effect; Macrophage repolarization; Nanomedicine; RONS scavenging; Rheumatoid arthritis; Self-assembly strategy.