Ratiometric NIR-II fluorescent organic nanoprobe for imaging and monitoring tumor-activated photodynamic therapy

Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment due to its non-invasiveness and high selectivity. However, the off-target activation of phototoxicity and the limited availability of tumor-specific biomarkers pose challenges for effective PDT. Here, we present the development of a novel ratiometric near-infrared-II (NIR-II) fluorescent organic nanoprobe, BTz-IC@IR1061, which responds specifically to hypochlorite (HClO) within tumors. This nanoprobe allows ratiometric fluorescence imaging to monitor and guide activated tumor PDT. BTz-IC@IR1061 nanoparticles were synthesized by codoping the small molecule dye BTz-IC, which generates reactive oxygen species (ROS), with the commercial dye IR1061. The presence of HClO selectively activates the fluorescence and photodynamic properties of BTz-IC while destroying IR1061, enabling controlled release of ROS for tumor therapy. We demonstrated the high selectivity of the nanoprobe for HClO, as well as its excellent photostability, photoacoustic imaging capability, and photothermal effects. Furthermore, in vivo studies revealed effective tumor targeting and remarkable tumor growth inhibition through tumor-activated PDT. Our findings highlight the potential of BTz-IC@IR1061 as a promising tool for tumor-specific PDT, providing new opportunities for precise and controlled cancer therapy.