Advanced nanoplatforms for precise intervention of synovial inflammation in rheumatoid arthritis

As a chronic systemic autoimmune disease, rheumatoid arthritis (RA) is characterized by persistent synovial inflammation, progressive joint destruction, and substantial long-term disability. These arthritic symptoms are mainly driven by fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS) via secreting pro-inflammatory cytokines, matrix-degrading enzymes, and osteoclast-activating factors. Considerable systemic side effects and drug resistance constrain conventional pharmacotherapies. In recent years, various nanoplatforms have demonstrated significant potential in achieving precise drug delivery and multimodal therapeutic modulation in RA. However, few reviews have centered on MLS and FLS as the framework and elaborated on the corresponding treatment strategies of RA. This review first elucidates the key mechanistic roles of FLS and MLS in RA pathogenesis, then systematically categorizes the design principles of advanced nanoplatforms for targeting or regulating these synovial cell subsets. Moving beyond single-cell or single-pathway intervention, we highlight emerging nanotherapeutic strategies that achieve system-level modulation of the inflammatory synovial microenvironment. We further discuss the major challenges facing nanoplatform-based precision therapy and propose future directions. Ultimately, this review proposes a logical framework centered on FLS and MLS and integrates dual-cell regulation, adaptive microenvironment-response, and immune-metabolic reprogramming strategies, which can accelerate the widespread translation of advanced nanoplatforms and provide a systematic roadmap for more effective and precise management of RA.