Lu Beilei, Li Cuixian, Jing Luxia, Zhuang Fan, Xiang Huijing, Chen Yu, Huang Beijian
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.
Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, PR China.
J Control Release. 2023 Oct;362:631-646. doi: 10.1016/j.jconrel.2023.09.012. Epub 2023 Sep 17.
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.
炎症细胞尤其是巨噬细胞的浸润，与活性氧和氮物种（RONS）的产生以及炎性细胞因子的释放相结合，在类风湿性关节炎（RA）的发病机制中起着关键作用。RONS清除与巨噬细胞从促炎性M1表型向抗炎性M2表型的重新极化的协同组合，为有效的RA治疗提供了一种有前景的策略。在此，本研究报道了一种独特的自组装策略，使用天然存在的基于多酚的化合物迷迭香酸（RosA）构建不同的迷迭香酸纳米颗粒（RNP）用于有效的RA治疗。所设计的RNP在清除巨噬细胞产生的RONS和促炎细胞因子方面表现出良好的能力。由于炎症部位血管内皮细胞间隙增宽，RNP可以靶向并积聚在胶原诱导性关节炎（CIA）大鼠的炎性关节处，以确保治疗效果。体内研究表明，RNP减轻了RA的症状，包括CIA大鼠的关节肿胀、滑膜增生、软骨降解和骨侵蚀。此外，所设计的RNP促进巨噬细胞从M1表型向M2表型极化，从而抑制RA的进展。因此，本研究代表了使用源自天然多酚类化合物的抗氧化纳米药物治疗RA的典型范例。
