Immuno-modulating theranostic gold nanocages for the treatment of rheumatoid arthritis in vivo

•PEGylated FA and IL-4-conjugated AuNCs as a targeting theranostic medicine for RA.•Methylprednisolone and IL-4 conjugated AuNCs promoted M2 macrophage repolarization.•Functionalized AuNCs had excellent theranostic efficacy of RA in vivo. The chronic autoimmune of rheumatoid arthritis (RA) usually results in inflammation of synovial joint, leading to pain, and destruction of cartilage and bone. Activated macrophages (M1 macrophages) actively take part in the RA pathogenesis, intensifying the inflammation and destruction of bone and cartilage. In this study, a nanoplatform was developed by grafting PEGylated folate acid (FA) and conjugating IL-4 onto gold nanocages (AuNCs), into the nanopores of which anti-inflammatory drug methylprednisolone (MP) was loaded. The IL-4@AuNCs conjugates (consisting of PEGylated FA, IL-4 and MP) effectively targeted the folate receptors overexpressed on M1 macrophage surface, down-regulating the expression of M1 marker and up-regulating the M2 markers. The expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β was significantly suppressed by the MP-AuNCs and IL-4@AuNCs both in vitro and in vivo. The AuNCs conjugates could act as a contrast agent for photoacoustic (PA) phantom and CT imaging. The therapeutic efficacy of different AuNCs conjugates on RA in a model of rat adjuvant-induced arthritis (AIA) was verified by ELISA, histological, and Western blot analyses, revealing the therapeutic potential through immune-modulatory function on macrophages with IL-4@AuNCs being the best and followed by MP-AuNCs.