Optimizing energy transfer in NIR ruthenium(II) complexes to enhance stability and efficiency in sonodynamic therapy

Recent advancements in nanomedicine have driven the development of multifunctional theranostic platforms for targeted cancer therapy. Sonodynamic therapy (SDT) holds a distinct advantage over traditional photodynamic therapy (PDT) by harnessing ultrasound-triggered sonosensitizer activation, enabling deeper tissue penetration for treating deep-seated tumors. In this study, we present IR780-TPEY-Ru, a nanoplatformspecifically engineered for imaging-guided SDT to address challenges posed by deep-seated tumors. This platform is engineered through the synergistic integration of π-expansive ligands (IR780) with tetraphenylethylene (TPE), yielding a distinct Ru(II) complex that possesses exceptional electronic and structural properties, particularly in the near-infrared (NIR) region. Significant progress has been achieved through the integration of π-expanded tridentate ligands, which facilitate the generation of low-lying intraligand (³IL) and intraligand charge transfer (³ILCT) states, with ligands that enhance near-infrared absorption characteristics. The optimized IR780-TPEY-Ru exhibits both NIR-enabled bioimaging capabilities and exceptional therapeutic potential, particularly for deep-seated tumors, due to its sustained response to ultrasound stimulation. This study offers a promising strategy for developing tailored sonosensitizers for imaging-guided sonodynamic therapy.