Diversified photo-energy conversion based on single-molecule FRET to realize enhanced phototheranostics

Phototheranostics, the integration of phototherapy and multimodal imaging into one nanoagent, is highly significant for precise cancer treatment, during which how the photo-energy is converted plays a critical role. The Förster resonance energy transfer (FRET) mechanism has opened up a new avenue for diversifying energy conversion, demonstrating great promise for enhanced phototheranostics. Herein, a theranostic nanoagent (HCY–TPA), based on single-molecule FRET, was designed, where the harvested photo-energy was not only transformed into near-infrared fluorescence but also acoustic energy for deep-seated tumor imaging, as well as enhanced thermal and type-I ROS generation for efficient treatment, realizing optimized phototheranostics. Furthermore, the dual cation endowed it with superior mitochondrial targeting ability for precise treatment. In vivo mouse model experiments demonstrated that the proliferation of tumors was effectively inhibited, compared to that by single HCY or TPA, which ultimately demonstrated a synergistic effect in multimodal imaging guiding synergistic cancer treatment.