title: Scavenger Receptor-Mediated Targeted Treatment of Collagen-Induced Arthritis by Dextran Sulfate-Methotrexate Prodrug.
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.
authors.affiliation: 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.
authors.forename: Modi
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ding
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
authors.forename: Xiangru
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chang
authors.affiliation: Institute of Immunology, Academy of Translational Medicine, First Hospital of Jilin University, Changchun 130021, P. R. China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China.
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000473:pathology / Q000628:therapy*; D016264:Dextran Sulfate / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006651:Histocytochemistry; D007719:Knee Joint / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008811:Mice, Inbred DBA; D011355:Prodrugs / Q000008:administration & dosage*; D000067996:RAW 264.7 Cells; D051116:Receptors, Scavenger / Q000819:agonists*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D011355:Prodrugs; D051116:Receptors, Scavenger; D016264:Dextran Sulfate; D008727:Methotrexate
keywords: collagen-induced arthritis; controlled release; methotrexate prodrug; rheumatoid arthritis therapy.; scavenger receptor