基于光敏剂的光疗,包括光动力疗法(PDT)和光热疗法(PTT),为时空精确的肿瘤消融提供安全的治疗方式。光子被吸收后,PDT通过产生活性氧(ROS)产生局部化学损伤,而PTT引起局部热损伤。然而,PDT仍然面临着肿瘤缺氧的挑战,而PTT遇到与耐热性和潜在过热相关的问题。PDT和PTT的组合显示出作为有效抗癌策略的巨大潜力。通过使用精心设计的光疗试剂针对溶酶体进行联合光疗,可以诱导癌细胞的快速功能障碍和细胞死亡,显示出癌症治疗的希望。在这里,设计并合成了两个具有四苯基乙烯(TPE)部分的α-α-连接的双BODIPY。这些TPE取代的双BODIPY将吸收扩展到NIR范围(λmaxabs/λmaxem〜740/810nm),并赋予聚集诱导发射(AIE)活性(λmaxem〜912nm)。此外,这些双BODIPY与表面活性剂F-127自组装成纳米颗粒(NP),在溶液和细胞环境中有效地产生ROS(1O2和•OH),并表现出优异的光热转换效率(η〜68.3%)以及出色的光热稳定性。更重要的是,这些NP在细胞和小鼠模型中显示溶酶体靶向和显着的肿瘤消融,表明他们在精确肿瘤治疗中的潜力。
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.