Near-infrared small molecule coupled with rigidness and flexibility for high-performance multimodal imaging-guided photodynamic and photothermal synergistic therapy

Photodynamic therapy (PDT) synergized photothermal therapy (PTT) shows superior clinical application prospects than single PDT or PTT. On the other hand, multimodal imaging can delineate comprehensive information about the lesion site and thus help to improve therapy accuracy. However, integrating all these functions into one single molecule is challenging, let alone balancing and maximizing the efficacy of each function. Herein, a near-infrared (NIR) small molecule (ETTC) with an "acceptor-donor-acceptor"structure was designed and synthesized by coupling rigity and flexibility to simultaneously achieve NIR-II fluorescence imaging (NIR-II FLI), photoacoustic imaging, PTT and PDT. The efficacy of each functionality was well balanced and optimized (NIR-II quantum yield: 3.0%; reactive oxygen species generation: 3.2-fold higher than ICG; photothermal conversion efficiency: 52.8%), which may be attributed to the coupling of the rigid and flexible structures in ETTC to tactically manipulate the energy dissipation paths (non-radiative against radiative decay). As a proof-of-concept, under the effective guidance of local-tumor imaging by PA and whole-body imaging by NIR-II FL, complete tumor eradication was achieved via PDT and PTT combinational therapy. This work provides a novel perspective into conceiving and developing single molecule for efficient versatile biomedical applications.