Metal−organic framework derived multicomponent nanoagent as a reactive oxygen species amplifier for enhanced photodynamic therapy

• Main Authors: Wang, Dongdong, Wu, Huihui, Yang, Guangbao, Qian, Cheng, Gu, Long, Wang, Hou, Zhou, Weiqiang, Liu, Jiawei, Wu, Yinglong, Zhang, Xiaodong, Guo, Zhen, Chen, Hongzhong, Jana, Deblin, Zhao, Yanli
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Medicine; Glutathione; Metal-organic Frameworks
• Online Access: https://hdl.handle.net/10356/146323
• Institution: Nanyang Technological University

Intracellular antioxidants such as glutathione (GSH) play a critical role in protecting malignant tumor cells from apoptosis induced by reactive oxygen species (ROS) and in mechanisms of multidrug and radiation resistance. Herein, we rationally design two multicomponent self-assembled photodynamic therapy (PDT) nanoagents, that is, Glup-MFi-c and Glud-MFo-c, which consist of respective GSH-passivation and GSH-depletion linkers in metal−organic frameworks encapsulated with photosensitizers for a deeply comprehensive understanding of GSH-based tumor PDT. Multicomponent coordination, π−π stacking, and electrostatic interactions among metal ions, photosensitizers, and bridging linkers under the protection of a biocompatible polymer generate homogeneous nanoparticles with satisfied size, good colloid stability, and ultrahigh loading capacity. Compared to the GSH-passivated Glup-MFi-c, the GSH-depleted Glud-MFo-c shows pH-responsive release of photosensitizer and [FeIII(CN)6] linker in tumor cells to efficiently deplete intracellular GSH, thus amplifying the cell-killing efficiency of ROS and suppressing the tumor growth in vivo. This study demonstrates that Glud-MFo-c acts as a ROS amplifier, providing a useful strategy to deeply understand the role of GSH in combating cancer.