Strategic modification of outer branched side chains in multi-modal phototheranostic nanoplatform for synergistic breast cancer therapy.

Multi-modal imaging guided photothermal therapy (PTT) combined with photodynamic therapy (PDT) has shown significant advantages in breast cancer treatment. However, the development of superior phototheranostic nanoagents remains highly challenging. Herein, a "one-for-all" phototheranostic nanoagent was developed based on a fused-ring small molecule (L8-4F), which was functionalized with outer butyloctyl branched side chains for poor molecular planarity and loose intermolecular π-π stacking. The water-soluble L8-4F nanoparticles (NPs) prepared by the nano-precipitation method not only exhibited strong near-infrared I (NIR-I) absorption, a large Stokes shift (108 nm), and near-infrared II (NIR-II) emission in the range of 835-1200 nm, but also achieved a photothermal conversion efficiency (PCE) as high as 58 % under 808 nm laser irradiation, while simultaneously generating type-I superoxide radicals (•O₂-). In animal experiments, high-resolution vascular imaging and accurate tumor localization were achieved in 4T1 tumor bearing mice using L8-4F NPs via integrated fluorescence imaging (FLI) and photoacoustic imaging (PAI). Moreover, the synergistic combination of photothermal therapy (PTT) and type-I photodynamic therapy (PDT) provided effective strategy for breast cancer treatment. In general, this study presented valuable guidance for constructing efficient "one-for-all" phototheranostic nanoagent.