Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment

• Published in: Bioactive materials Vol. 24; pp. 37 - 53
• Main Authors: Shen, Haotian, Jin, Lulu, Zheng, Qiangqiang, Ye, Ziqiang, Cheng, Linxiang, Wu, Yuxu, Wu, Honghao, Jon, Tae Gyong, Liu, Wenduo, Pan, Zongyou, Mao, Zhengwei, Wang, Yue
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.06.2023; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Drug delivery; Inflammation; Mesoporous nanoparticles; Rheumatoid arthritis; STING; STING; Inflammation; Drug delivery; Rheumatoid arthritis; Mesoporous nanoparticles
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2022.12.001

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. Schematic illustration of (A) the Chemical Composition of PEI-PDA@C-176 NPs and (B) the mechanism utilized for therapeutic of RA via inhibiting the STING pathway. [Display omitted] •We demonstrated significant accumulation of cell-free double stranded DNA (dsDNA) and STING activation played a pivotal role in Rheumatoid arthritis (RA) pathogenesis.•We synthesized a spherical polyethyleneimine coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176 (PEI-PDA@C-176 NPs).•The obtained PDA NPs adsorb dsDNA and release C-176, thus inhibit STING signaling simultaneously.•The obtained PDA NPs effectively reduce synovium and cartilage damage in both dsDNA-induced arthritis model and collagen induced arthritis model via synergetic STING inhibition.