Thermosensitive Light-Driven Smart Platform Induces Apoptosis of Fibroblast-like Synovial Cells and Macrophages for Enhanced Rheumatoid Arthritis Therapy.

Macrophage activation induces rapid proliferation and division of fibroblast-like synovial cells (FLSs), resulting in the degradation of cartilage matrix and bone destruction, which are the main pathological characteristics of rheumatoid arthritis (RA). Inducing apoptosis in these inflammatory cells to mitigate the inflammatory response and alleviate bone damage is a potential therapeutic strategy for RA. In this study, we developed a smart platform for synergistic photothermal therapy (PTT) and chemotherapy by utilizing hyaluronic acid (HA)-modified thermally sensitive liposomes loaded with celastrol (CEL) and gold nanorods (GNRs), termed HA/Lipo-CEL-GNRs, for application in a rat RA model. Under laser irradiation, GNRs exhibited excellent photothermal effects due to localized surface plasmon resonance. The resulting increase in temperature not only effectively eliminated hyperproliferative inflammatory cells in the joints but also triggered CEL release from the thermosensitive liposomes, significantly increasing its concentration in the synovium. The synergistic effect of PTT and chemotherapy significantly promoted the apoptosis of FLSs and macrophages and effectively suppressed the inflammatory response in the RA microenvironment. In summary, multifunctional thermosensitive HA/Lipo-CEL-GNRs represent promising nanotherapeutic platforms capable of achieving light-driven enrichment of heat and therapeutic agents, significantly preventing the progression of RA.