NIR-Absorbing Tetraphenylethene-Containing bisBODIPY Nanoplatforms Demonstrate Effective Lysosome-Targeting and Combinational Phototherapy

Photosensitizer-based phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), offer safe treatment modalities for tumor ablation with spatiotemporal precision. After photons are absorbed, PDT creates localized chemical damage by generating reactive oxygen species (ROS), while PTT induces localized thermal damage. However, PDT still faces hypoxic tumor challenges, while PTT encounters issues related to heat resistance and potential overheating. The combination of PDT and PTT shows great potential as an effective anticancer strategy. By targeting lysosomes with carefully designed phototherapeutic reagents for combined phototherapy, rapid dysfunction and cell death in cancer cells can be induced, showing promise for cancer treatment. Herein, two α–α-linked bisBODIPYs with tetraphenylethene (TPE) moieties are designed and synthesized. These TPE-substituted bisBODIPYs expand the absorption into NIR range (λmaxabs/λmaxem ∼ 740/810 nm) and confer aggregation-induced emission (AIE) activity (λmaxem ∼ 912 nm). Moreover, these bisBODIPYs self-assemble with surfactant F-127 into nanoparticles (NPs), which efficiently generate ROS (1O2 and •OH) in both solution and cellular environments and demonstrate superior photothermal conversion efficiencies (η ∼ 68.3%) along with exceptional photothermal stability. More importantly, these NPs showed lysosomal targeting and remarkable tumor ablation in cellular and murine models, indicating their potential in precision tumor therapy.