A Smart Visualized Phototherapy Switch: From NIR-I Imaging-Guided Photodynamic Therapy to NIR-II-Guided Photothermal Therapy for Enhanced Cascade Tumor Photoablation

Abstract

Imaging-guided phototherapy holds promise for precision cancer treatment. However, most photosensitizers have only a singular modality of photodynamic therapy (PDT) or photothermal therapy (PTT), which make their therapeutic efficacy severely limited by the hypoxic and complex tumor microenvironment (TME). In this article, we provide a smart platform design (BOD-D) based on a visualized light-triggered phototherapeutic switch for transforming cancer therapy from near-infrared (NIR)-I imaging-guided PDT to activatable NIR-II-guided PTT while releasing nitric oxide (NO) for gas therapy (GT). BOD-D releases native NIR one-region fluorescence signals in tumors, which is used to direct robust PDT for tumor killing. As PDT is administered, the decreasing oxygen content in TME becomes progressively insufficient to maintain its excellent cell-killing effect. Subsequently, light triggers the dissociation of NO in BOD-D, activating a photothermal agent BOD-T that emits NIR-II fluorescence, for subsequent PTT. Notably, not only the light-mediated therapeutic mechanism can be switched from NIR-I-guided PDT to NIR-II-guided PTT, but also the NO released during this process will be used for GT to sensitize the above PDT and PTT. Our study contributes to the design of intelligent photosensitizers for cascade tumor photoablation.