A Viscosity-Responsive Mitochondria-Targeting Ir(III) Probe for Inducing and Monitoring Photodynamic-Triggered Ferroptosis

Colorectal cancer (CRC) is a major cause of cancer-related death, with poor outcomes at advanced stages due to metastasis and limited early detection. Photodynamic therapy (PDT), which relies on reactive oxygen species (ROS) to kill tumor cells, is promising but limited by hypoxia and short ROS diffusion distances. Here, we report Ir-EA, a novel cyclometalated Ir(III) complex with enhanced mitochondrial targeting and dual ROS generation capability, effective under both oxygen-rich and hypoxic conditions. Ir-EA induces ferroptosis, a form of oxidative stress-related cell death, offering a strategy to overcome drug resistance. Additionally, Ir-EA exhibits viscosity-sensitive fluorescence, enabling real-time monitoring of mitochondrial microviscosity changes during ferroptosis. This dual functionality─therapeutic induction and diagnostic imaging─enhances the efficacy of PDT and provides a noninvasive means to assess therapeutic responses. Overall, Ir-EA represents a promising platform for improving cancer treatment and advancing theranostic applications.