Lysosomal peroxynitrite imaging reveals oxidative stress and therapeutic response in osteoarthritis using a...

Osteoarthritis (OA) is closely associated with oxidative and nitrosative stress, in which peroxynitrite (ONOO^-) contributes to inflammatory damage and cartilage degeneration. Given the involvement of lysosomal dysfunction in OA, lysosomal ONOO^- imaging may provide valuable information on disease progression and therapeutic response. Herein, we developed a lysosome-targeted fluorogenic probe, Lys-ONOO, for sensitive ONOO^- detection in living systems. Lys-ONOO exhibited a rapid and selective response toward ONOO^- with a detection limit of 11.4 nM and enabled imaging of both exogenous and endogenous ONOO^-. The probe showed effective lysosomal localization and was successfully applied in cells, zebrafish, and murine OA models. Elevated ONOO^- signals were observed in osteoarthritic joints, whereas pharmacological treatment markedly reduced the fluorescence response. These findings demonstrate the potential of Lys-ONOO for lysosomal ONOO^- imaging, OA assessment, and therapeutic efficacy evaluation.