Nanocatalytic anti-inflammatory therapy for alleviating rheumatoid lesions with endothelial cell-derived hydrosilicene

Severe inflammatory damage of soft tissues and progressive bone destruction are hallmark features of rheumatoid arthritis (RA), in which over-activated neutrophils and excessive neutrophil extracellular traps (NETs) play a pivotal role during the early stages of the disease. Conventional drug therapies, such as methotrexate (MTX), are often insufficient in clinical practice, highlighting the urgent need for more targeted and definitive interventions at disease onset. Recently, accumulating evidences indicate that reactive oxygen species (ROS) act as a key trigger for NETs formation. In this study, we developed a biomimetic nanocatalytic system by coating hydrosilicene (HSI) nanosheets with natural endothelial cell membranes (HSI@ECM). This bio-inspired design mimicked typical endothelial-neutrophil adhesion, enabling targeted delivery of the nanosystem to over-activated neutrophils at the inflammatory sites. The fabricated HSI@ECM subsequently released hydrogen gas in situ and selectively scavenged excessive ROS within the neutrophils, thereby inhibiting NETs formation and preserving mitochondrial function. In vivo experiments in a collagen-induced arthritis (CIA) mouse model demonstrated that HSI@ECM significantly alleviated joint swelling, inflammatory cell infiltration and cartilage-bone damage, outperforming both the uncoated nanosheets and MTX. Overall, this work presents a nanocatalytic anti-inflammatory therapeutic strategy with promising potential for mitigating rheumatoid soft tissue, cartilage and bone damage.