Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment  

作　　者：Haotian Shen Lulu Jin Qiangqiang Zheng Ziqiang Ye Linxiang Cheng Yuxu Wu Honghao Wu Tae Gyong Jon Wenduo Liu Zongyou Pan Zhengwei Mao Yue Wang 

机构地区：[1]Department of Orthopedic Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310003,China [2]MOE Key Laboratory of Macromolecular Synthesis and Functionalization,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou,310027,China [3]Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cells and Regenerative Medicine,Zhejiang University School of Medicine,Hangzhou,310000,China [4]International Institutes of Medicine,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,N1 Shangchen Road,Yiwu,Zhejiang,322000,China

出　　处：《Bioactive Materials》2023年第6期37-53,共17页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(81772382,22161132027 and 82102599);the Key Research Program in Zhejiang Province,Science Technology Department of Zhejiang Province(2020C03042);the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-006).

摘　　要：Rheumatoid arthritis(RA)is a common autoimmune disease leading to pain,disability,and even death.Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases,the role of STING in RA remains unclear.In the current study,we demonstrated that STING activation was pivotal in RA pathogenesis.As the accumulation of dsDNA,a specific stimulus for STING,is a feature of RA,we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176(PEI-PDA@C-176 NPs)for treating RA.The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages.Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway.We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA.

关 键 词：Mesoporous nanoparticles STING INFLAMMATION Drug delivery Rheumatoid arthritis 

分 类 号：R593.22[医药卫生—内科学]