Here, we have synthesized and characterized a novel activatable photosensitizer (PS) 8a in which two well-designed boron dipyrromethene (BODIPY) derivatives are utilized as the photosensitizing fluorophore and quencher respectively, which are connected by a disulfide linker via two successive Cu (І) catalyzed click reactions. The fluorescence emission and singlet oxygen production of 8a are suppressed via intramolecular fluorescence resonance energy transfer (FRET) from the excited BODIPY-based PS part to quencher unit, but both of them can be simultaneously switched on by cancer-related biothiol glutathione (GSH) in phosphate buffered saline (PBS) solution with 0.05% Tween 80 as a result of cleavage of disulfide. Also, 8a exhibits a bright fluorescence image and a substantial ROS production in A549 human lung adenocarcinoma, HeLa human cervical carcinoma and H22 mouse hepatoma cells having a relatively high concentration of GSH, thereby leading to a significant photocytotoxicity, with IC₅₀ values as low as 0.44 μM, 0.67 μM and 0.48 μM, respectively. In addition, the photosensitizer can be effectively activated and imaged in H22 transplanted hepatoma tumors of mice and shows a strong inhibition on tumor growth. All these results suggest that such a GSH-responsive photosensitizer based on FRET mechanism may provide a new strategy for tumor-targeted and fluorescence imaging-guided cancer therapy.

在此，我们合成并表征了一种新型可活化光敏剂（PS）8a，其中分别使用两种设计良好的硼二吡咯亚甲基（BODIPY）衍生物作为光敏荧光团和猝灭剂，它们通过二硫键通过两个连续的Cu（І）连接。 ）催化的点击反应。通过分子内的荧光共振能量转移（FRET）从基于BODIPY的PS部分激发到猝灭剂单元，可以抑制8a的荧光发射和单线态氧的产生，但是这两者都可以通过癌症相关的生物硫醇谷胱甘肽（GSH）同时开启由于二硫键裂解，在含0.05％Tween 80的磷酸盐缓冲盐水（PBS）溶液中溶解。还有8a在具有相对较高GSH浓度的A549人肺腺癌，HeLa人宫颈癌和H22小鼠肝癌细胞中显示出明亮的荧光图像并产生大量ROS，从而导致显着的光细胞毒性，IC ₅₀值低至0.44μM，分别为0.67μM和0.48μM。此外，该光敏剂可以在小鼠H22移植的肝癌肿瘤中有效激活并成像，并显示出对肿瘤生长的强烈抑制作用。所有这些结果表明，这种基于FRET机制的GSH响应型光敏剂可能为肿瘤靶向和荧光成像指导的癌症治疗提供新的策略。