Wang Shi-Yin, Chen Guo, Chen Ji-Feng, Wang Jin, Deng Shao-Hui, Cheng Du
PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University Guangzhou 510275 P. R. China
Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University Guangzhou 510630 P. R. China.
RSC Adv. 2022 Aug 3;12(33):21609-21620. doi: 10.1039/d2ra01877b. eCollection 2022 Jul 21.
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. and 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.
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ROS会被肿瘤细胞中高浓度的谷胱甘肽（GSH）消耗，严重损害PDT的治疗效果。在此，我们合成了一种清除GSH的共聚物来递送光敏剂二氢卟吩e6（Ce6）。与其他二硫键基团相比，与GSH的巯基反应更快的吡啶二硫键基团被接枝到疏水嵌段上以包封Ce6。在近红外照射下，Ce6产生活性氧以杀死肿瘤细胞，吡啶二硫键基团消耗GSH以防止活性氧的消耗，从而协同增强了PDT的治疗效果。 实验证实了Ce6诱导的活性氧生成和吡啶二硫键基团诱导的GSH消耗的联合抗肿瘤作用。因此，接枝吡啶二硫键基团的两亲共聚物为增强PDT提供了一种更有效的策略，并具有广阔的临床应用前景。
