An in-situ hydrogel loaded with PEI-SS-IND-MTX-MMP-9 siRNA NPs (D/siRNA-NGel) was used to simultaneously deliver three drugs (indomethacin (IND), MTX, and MMP-9 siRNA) for treating RA by targeting multiple signaling pathways.315 The MMP-9 siRNA inhibited MMP-9 expression and the cartilage degeneration mediated by RA synovial fibroblasts; at the same time, the anti-inflammatory drug IND relieved patients’ pain, coupled with the fundamental anti-rheumatic effect of MTX. The gene discussed is MMP9; the disease is rheumatoid arthritis.