Breaking the reduced glutathione-activated antioxidant defence for enhanced photodynamic therapy
Qi-Chen Zhan1, Xian-Qing Shi, Xiao-Hong Yan
1College of Chemistry and Materials Science, Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry, Nanjing Normal University Nanjing (210023), P. R. China. zhoulin@njnu.edu.cn shwei@njnu.edu.cn.
Abstract:
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.
