Generation of Hydroxyl Radical-Activatable Ratiometric Near-Infrared Bimodal Probes for Early Monitoring of Tumor Response to Therapy

Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL 780 /FL 1113 ), but a small PA ratio between 755 and 905 nm (PA 755 /PA 905 ). Oxidation of 1-Br-Et by •OH decreases the FL 780 /FL 1113 while concurrently increasing the PA 755 /PA 905 , allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy.