In this work, CEL, a pentacyclic triterpenoid that belongs to the root of Tripterygium wilfordii [25–27], was loaded in PECT nanoparticles to target the TLR4/nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway and mediate the cross-talk of macrophage and synovial fibroblasts, aiming to mitigate the chronic inflammation and block the progression of RA. Here, NFKB1 is linked to rheumatoid arthritis.