The therapeutic effect of photodynamic therapy (PDT) is highly dependent on the intracellular production of reactive oxygen species (ROS). However, the ROS generated by photosensitizers can be consumed by the highly concentrated glutathione (GSH) in tumor cells, severely impairing the therapeutic effect of PDT. Herein, we synthesized a GSH-scavenging copolymer to deliver photosensitizer chlorin e6 (Ce6). The pyridyl disulfide groups, which have faster reactivity with the thiol groups of GSH than other disulfide groups, were grafted onto a hydrophobic block to encapsulate the Ce6. Under NIR irradiation, the Ce6 generated ROS to kill tumor cells, and the pyridyl disulfide groups depleted the GSH to prevent ROS consumption, which synergistically enhanced the therapeutic effect of PDT. In vitro and in vivo experiments confirmed the combinatory antitumor effect of Ce6-induced ROS generation and the pyridyl disulfide group-induced GSH depletion. Therefore, the pyridyl disulfide group-grafted amphiphilic copolymer provides a more efficient strategy for enhancing PDT and has promising potential for clinical application.

中文翻译：

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谷胱甘肽消耗聚合物提供二氢卟酚 e6 用于增强光动力疗法

光动力疗法 (PDT) 的治疗效果高度依赖于细胞内活性氧 (ROS) 的产生。然而，光敏剂产生的活性氧会被肿瘤细胞中高浓度的谷胱甘肽（GSH）消耗掉，严重影响了光动力疗法的治疗效果。在此，我们合成了一种 GSH 清除共聚物以提供光敏剂二氢卟酚 e6 (Ce6)。与其他二硫基团相比，与 GSH 的硫醇基团具有更快反应性的吡啶基二硫基团被接枝到疏水嵌段上以封装 Ce6。在 NIR 照射下，Ce6 产生 ROS 杀死肿瘤细胞，吡啶基二硫化物基团耗尽 GSH 以防止 ROS 消耗，协同增强了 PDT 的治疗效果。体外和体内实验证实了 Ce6 诱导的 ROS 产生和吡啶基二硫化物基团诱导的 GSH 耗竭的组合抗肿瘤作用。因此，吡啶基二硫化物基团接枝的两亲共聚物为增强PDT提供了一种更有效的策略，具有广阔的临床应用潜力。