1. Scavenger Receptor-Mediated Targeted Treatment of Collagen-Induced Arthritis by Dextran Sulfate-Methotrexate Prodrug
- Author
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Xiangru Feng, Xiuli Zhuang, Zhongli Gao, Modi Yang, Xuesi Chen, Jianxun Ding, Fei Chang, and Yinan Wang
- Subjects
musculoskeletal diseases ,Knee Joint ,rheumatoid arthritis therapy ,medicine.medical_treatment ,Anti-Inflammatory Agents ,Medicine (miscellaneous) ,Inflammation ,02 engineering and technology ,Pharmacology ,010402 general chemistry ,collagen-induced arthritis ,01 natural sciences ,Targeted therapy ,scavenger receptor ,Mice ,chemistry.chemical_compound ,methotrexate prodrug ,medicine ,Animals ,Prodrugs ,Scavenger receptor ,Receptor ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Receptors, Scavenger ,Histocytochemistry ,business.industry ,Macrophages ,Dextran Sulfate ,Prodrug ,021001 nanoscience & nanotechnology ,medicine.disease ,Arthritis, Experimental ,0104 chemical sciences ,Disease Models, Animal ,Methotrexate ,RAW 264.7 Cells ,Treatment Outcome ,Dextran ,chemistry ,Mice, Inbred DBA ,Rheumatoid arthritis ,Immunology ,medicine.symptom ,controlled release ,0210 nano-technology ,business ,Research Paper ,medicine.drug - Abstract
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-graft-methotrexate conjugate (DS-g-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-g-MTX, compared to the treatment with dextran-graft-methotrexate (Dex-g-MTX), as is confirmed by the detection of histopathology and pro-inflammatory cytokines. Our work highlights DS-g-MTX as a potential therapeutic option for RA aiming the SR-expressed activated macrophages.
- Published
- 2017