A TME-activated photothermal agent with photodegradability for accurate breast tumor photothermal therapy

Photothermal therapy (PTT) has garnered significant attention due to its high controllability and minimal invasiveness. However, PTT remains hindered by the non-specificity and biosafety concerns associated with traditional photothermal agents. In this work, we successfully developed a tumor microenvironment (TME)-activated intelligent photothermal agent, IR780-PDA, which exhibits a GSH-activated photophysical transformation. The absorption peak of IR780-PDA red-shifts from 640 nm to 790 nm, markedly enhancing its photothermal conversion efficiency under near-infrared laser irradiation. Additionally, IR780-PDA possesses dual-wavelength photoacoustic imaging capabilities at 640 nm and 790 nm, facilitating accurate tumor localization and real-time imaging monitoring. Under conditions of high GSH levels and 808 nm laser irradiation, IR780-PDA undergoes photodegradation, promoting efficient <i>in vivo</i> metabolism and improving biosafety. Animal experiments demonstrated that IR780-PDA achieves specific tumor enrichment in breast cancer models and completely eradicates tumors, showcasing excellent therapeutic efficacy and good biocompatibility.