硫酸葡聚糖-甲氨蝶呤前药通过清道夫受体介导的胶原诱导性关节炎靶向治疗

Scavenger Receptor-Mediated Targeted Treatment of Collagen-Induced Arthritis by Dextran Sulfate-Methotrexate Prodrug.

作者信息

Yang Modi, Ding Jianxun, Feng Xiangru, Chang Fei, Wang Yinan, Gao Zhongli, Zhuang Xiuli, Chen Xuesi

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China;; Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

出版信息

Theranostics. 2017 Jan 1;7(1):97-105. doi: 10.7150/thno.16844. eCollection 2017.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder implicated in multiple joint affection and even disability. The activated macrophages perform a predominant role in onset and persistence of RA. Scavenger receptor (SR), one of several receptors overexpressed on the activated macrophages, is a specific biomarker for targeted therapy of numerous chronic inflammation diseases like RA. In this work, dextran sulfate--methotrexate conjugate (DS--MTX) is synthesized and characterized, which exhibits excellent targetability to SR on the activated RAW 264.7 cells. Additionally, the enhanced accumulation and potent inflammatory inhibition are observed in the affected joint after intravenous injection of DS--MTX, compared to the treatment with dextran--methotrexate (Dex--MTX), as is confirmed by the detection of histopathology and pro-inflammatory cytokines. Our work highlights DS--MTX as a potential therapeutic option for RA aiming the SR-expressed activated macrophages.

类风湿性关节炎（RA）是一种慢性自身免疫性疾病，可累及多个关节甚至导致残疾。活化的巨噬细胞在RA的发病和持续过程中起主要作用。清道夫受体（SR）是活化巨噬细胞上过度表达的几种受体之一，是针对RA等多种慢性炎症疾病进行靶向治疗的特异性生物标志物。在这项工作中，合成并表征了硫酸葡聚糖 - 甲氨蝶呤缀合物（DS - MTX），其对活化的RAW 264.7细胞上的SR表现出优异的靶向性。此外，与葡聚糖 - 甲氨蝶呤（Dex - MTX）治疗相比,静脉注射DS - MTX后，在受影响的关节中观察到增强的药物蓄积和强效的炎症抑制作用，这通过组织病理学和促炎细胞因子的检测得到证实。我们的工作突出了DS - MTX作为针对表达SR的活化巨噬细胞的RA潜在治疗选择的作用。