Endogenous nanoalbumin-based ROS cascade-amplification strategy for multi-treatment of rheumatoid arthritis

RuO 2 @BSA-ATO NG, an endogenous nano-albumin-based ROS cascade amplification strategy for multiple treatments of rheumatoid arthritis. • Easily enters cells and generates toxic hydroxyl radicals in RAs. • Contains ATO inhibiting cellular function and increasing H 2 O 2 levels. • PTT capability leads to increased generation of reactive ROS after cell lysis. Rheumatoid arthritis (RA) is deemed as chronic autoimmune syndrome, defined by the uncontrolled proliferation of rheumatoid arthritis synovial fibroblasts (RASFs). The existing clinical treatments, which are largely local anti-inflammatory therapies, have demonstrated restricted efficacy. Accordingly, the concurrent suppression/elimination of diseased tissues alongside anti-inflammatory efforts is increasingly regarded as a potential strategy to RA treatment. Our study designs a novel cascaded reaction nanoenzyme, RuO 2 @BSA-ATO NGs, with the intention of increasing endogenous hydrogen peroxide (H 2 O 2 ) levels to enhance reaction efficiency and induce targeted mitochondrial damage through hydroxyl radical generation. The RuO 2 @BSA-ATO NGs can enter cells easily and catalyze H 2 O 2 decomposition, thereby producing toxic hydroxyl radicals in RA. The loaded atovaquone (ATO) targets mitochondria, inhibits cellular functions and increases H 2 O 2 levels. The photothermal therapy (PTT) capability, resulting from high photothermal conversion efficiencies, leads to the increased generation of reactive oxygen species (ROS) following cell lysis. The RuO 2 @BSA-ATO NGs, developed for use in multi-therapy under near-infrared photoacoustic (PA) imaging, serves a vital function in the ablation of RASFs within the RA microenvironment. To conclude, the multifunctional cascaded reaction nanoenzyme RuO 2 @BSA-ATO NGs represents a promising approach to improve cellular eradication effectiveness under photonic guidance, offering new avenues for diagnosis and treatment of refractory RA.