炎症
类风湿性关节炎
医学
关节炎
免疫学
趋化因子
滑膜炎
药理学
癌症研究
化学
作者
Jiaxin Li,Yang Long,Rong Guo,Kebai Ren,Zhonghua Lu,Man Li,Xuhui Wang,Yashi Wang,Zhirong Zhang,Qin He
标识
DOI:10.1016/j.jconrel.2021.05.008
摘要
Rheumatoid arthritis (RA) is characterized by the outbreak of inflammation. Neutrophils, the main culprit of the outbreak of inflammation, are the first inflammatory cells to be recruited to inflamed joints and facilitate the recruitment of themselves by stimulating the release of chemokines. Here, based on neutrophils, a novel anti-inflammatory “shield and sword soldiers” strategy is established with LMWH-TOS nanoparticles (LT NPs). The hydrophilic fragment low molecular weight heparin (LMWH) acts as a shield which block the transvascular movement of neutrophils through inhibiting the adhesion cascade by binding to P-selectin on inflamed endothelium. Synergistically, MMP-9, which is secreted by the recruited neutrophils and degrade the main component of articular cartilage, is reduced by the hydrophobic fragment d-α-tocopheryl succinate (TOS), functioning as a sword. In collagen-induced arthritis (CIA) mouse model, LT NPs show significant targeting effect, and exhibit prominent therapeutic efficacy after enveloping the first-line anti-RA drug methotrexate. Our work proves that the multi-stage manipulation of neutrophils is feasible and effective, providing a new concept for RA treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI