GeSe Nanosheets-Mediated Local Sonocatalytic Immunosuppression of Rheumatoid Arthritis

Abstract

The first-line systemic administration of anti-rheumatic immunosuppressants unavoidably causes adverse effects such as the increase in the risk of infection. While the emergence of local drug delivery for rheumatoid arthritis (RA) therapy can effectively reduce systemic adverse effects, persistent RA therapy remains challenging. In this work, a local sonocatalytic immunosuppression strategy for persistent RA therapy without the use of traditional immunosuppressants is proposed, and develop GeSe nanosheets (GSN) with a high piezoelectric coefficient and a wide bandgap to realize efficient sonocatalytic H₂ production and lactic acid (LA) consumption within the articular cavity for combined immunosuppression, which restrains the deteriorate of RA. Mechanistically, locally generated H₂ inhibits the intraarticular levels of proinflammatory cytokines TNF-α, IFN-γ and receptor activator of nuclear factor-κB ligand (RANKL) by preventing the conversion of Th0 cells to Th1 cells, and consequently blocks the differentiation of macrophages into activated osteoclasts and the osteoclastic expression of LA. At the same time, sonocatalytic oxidation/consumption of LA eradicates the corrosion of LA to bone and cartilage. The proposed sonocatalytic immunosuppression strategy precedes photocatalysis owing to remarkably higher tissue penetrability of ultrasound than light and will open a window to realize efficient treatment of deep-seated immune-related diseases.