Tumor Site‐Specific In Vivo Theranostics Enabled by Microenvironment‐Dependent Chemical Transformation and Self‐Amplifying Effect

Precise tumor diagnosis and treatment remain complex challenges. While numerous fluorescent probes have been developed for tumor-specific imaging and therapy, few exhibit effective function in vivo. Herein, a probe called TQ-H₂ is designed that can realize robust theranostic effects both in vitro and in vivo. In vitro, TQ-H₂ specifically targets the lysosome and reacts with hydroxyl radical (·OH) to generate TQ-HA, which lights up the cells. TQ-HA generates reactive oxygen species (ROS) under light irradiation, enabling the simultaneous induction and monitoring of apoptosis and ferroptosis in tumor cells. Remarkably, TQ-HA also acts as a self-amplifier, autocatalytically activating TQ-H₂ by generating ·OH under light exposure. This self-amplification aligns with the tumor microenvironment, where TQ-H₂ undergoes chemical transformation, distinguishing tumors from healthy tissue via near-infrared (NIR) fluorescence imaging. Furthermore, ROS generated by TQ-HA effectively kills tumor cells and inhibits tumor growth without harming normal cells. This study offers a promising strategy for targeted tumor theranostics using self-amplifying microenvironment-responsive fluorescent probes.