An intelligent phototheranostic nanoplatform for controllable FRET-activated NIR-II imaging-guided phototherapy.

NIR-II imaging-guided phototherapy holds great promise for cancer therapy owing to its noninvasiveness and superior spatiotemporal controllability. However, conventional phototherapeutic agents usually suffer from an "always-on" behavior, which inevitably cause damage to normal tissues during treatment. Meanwhile, most NIR-II imaging agents exhibit low fluorescence quantum yield, leading to insufficient imaging quality and thus compromising diagnostic and therapeutic efficacy. Herein, we designed a fluorescence resonance energy transfer (FRET) -controllable intelligent nanoplatform (CR@CyP) for high-resolution NIR-II imaging and activatable antitumor therapy. The nanoplatform was co-assembled from a cyanine-based ROS-cleavable copolymer photosensitizer (CyP), a NIR-II fluorescent probe (CL), and an immune adjuvant (R837). FRET efficiently quenched photodynamic activity to maintain a "silent" state in blood circulation, enhancing biosafety, while increasing CL fluorescence for high-quality NIR-II imaging. Under 808 nm laser irradiation, in situ generated ROS cleaved thioketal groups in the polymer backbone, disrupting FRET and restoring phototherapeutic activity to achieve synergistic photodynamic and photothermal therapy. Furthermore, the damage-associated molecular patterns (DAMPs) induced by apoptotic tumor cells, and the R837 could trigger immunogenic cell death (ICD), thereby activating systemic antitumor immune responses. This strategy of controllable FRET-activatable NIR-II imaging-guided phototherapy would provide a promising approach for improving antitumor efficacy.