Breaking the reduced glutathione-activated antioxidant defence for enhanced photodynamic therapy
Breaking the reduced glutathione-activated antioxidant defence for enhanced photodynamic therapy
复制标题
打破还原型谷胱甘肽激活的抗氧化防御以增强光动力疗法
DOI：
10.1039/c7tb01233k
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发表时间：
2017
影响因子：
7
通讯作者：
Wei Shao hua
中科院分区：
文献类型：
--
作者：
Zhan Qi chen;Shi Xian qing;Yan Xiao hong;Liu Qian;Zhou Jia hong;Zhou Lin;Wei Shao hua
光动力疗法(PDT)利用活性氧(ROS)杀死癌细胞，已被应用于癌症的治疗。然而，癌细胞中存在高浓度的还原型谷胱甘肽(GSH)，可以消耗ROS并大幅降低PDT活性。针对这一问题，本文合成了胸腺嘧啶修饰的锌酞菁(ZnPc，PDT的单体和活性形式)，并以Hg2+为驱动力制备了其纳米颗粒(聚集体和非活性形式)，为胸腺嘧啶-Hg2+-胸腺嘧啶相互作用提供了驱动力。纳米粒子在血液中的传递过程中可能保持非活性状态。一旦被癌细胞吞噬，纳米颗粒就会被分解，并被细胞内的GSH剥夺Hg2+，从而降低GSH的水平。同时，释放的单体ZnPc的活性得到恢复，并观察到较高的PDT活性。
Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROSs) to kill cancer cells. However, a high concentration of reduced glutathione (GSH) is present in cancer cells and can consume ROSs and sharply reduce the PDT activity. To address this problem, herein, we synthesized a thymine modified Zn phthalocyanine (ZnPc, a monomer and an active form for PDT) and prepared its nanoparticle form (an aggregator and an inactive form) with Hg2+ providing the driving force for the “thymine–Hg2+–thymine” interaction. The nanoparticles could remain in the inactive form during the delivery process in blood. Once endocytosed by cancer cells, the nanoparticles are disintegrated, and deprived of Hg2+ by intracellular GSH, which decreases the level of GSH. Simultaneously, the activity of the released monomer ZnPc is recovered and high PDT activity is observed.