Mitochondria are crucial regulators of the intrinsic pathway of apoptosis. Herein, we report a photosensitizer-conjugated camptothecin (CPT)-based prodrug for combinative chemo-photodynamic treatment of solid tumors with cascade activations. Upon light irradiation, our prodrug can effectively target the mitochondria of cancer cells, generate singlet oxygen to increase the level of reactive oxygen species (ROS) and trigger ROS-responsive release of CPT, which synergistically induce mitochondrial damage and cause the apoptosis of cancer cells, therefore achieving high therapeutic efficacy for solid tumors and minimized adverse effects to normal tissues. Our prodrug holds great promise as a potent and inspiring means for cancer treatment.

中文翻译：

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喜树碱前药通过级联激活诱导癌细胞中线粒体介导的细胞凋亡

线粒体是细胞凋亡内在途径的关键调节剂。在此，我们报告了一种基于光敏剂偶联喜树碱 (CPT) 的前药，用于通过级联激活对实体瘤进行化学-光动力联合治疗。在光照射下，我们的前药可有效靶向癌细胞的线粒体，产生单线态氧以增加活性氧 (ROS) 的水平并触发 ROS 响应性的 CPT 释放，从而协同诱导线粒体损伤并导致癌细胞凋亡，从而实现对实体瘤的高治疗效果，并将对正常组织的不良影响降至最低。我们的前药有望成为一种有效且鼓舞人心的癌症治疗手段。