Activatable Chemodynamic Theranostics through Molecular Imaging-Energized Companion Diagnostics

Chemodynamic therapy (CDT) is a promising tumor treatment strategy, yet real-time <i>in vivo</i> monitoring remains challenging. Here, we report an activatable molecular imaging-energized companion diagnostics sensor (CFG) for real-time monitoring of CDT. CFG leverages glucose oxidase (GOx) to generate hydrogen peroxide to prime the Fenton reaction, while simultaneously producing H⁺ to activate the fluorescence (FL) and photoacoustic (PA) signals. A positive correlation between the FL/PA intensities and the Fenton reaction efficiency is found (Pearson's <i>r</i> = 0.98 for ·OH-FL, 0.90 for ·OH-PA), enabling dynamic visualization of the GOx catalysis-primed CDT. Also, H⁺-activated photothermal effect of CFG enables FL/PA imaging to pinpoint the optimal irradiation time for maximizing mild hyperthermia-enhanced CDT. Therefore, by tracing the H⁺ dynamics, tailored feedback is collected for therapeutic response monitoring and treatment guidance, and the cascade effect between enzyme catalysis, mild hyperthermia, and CDT is revealed.