Abstract
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 in vivo 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.