Metal-Organic Framework Derived Multicomponent Nanoagent as a Reactive Oxygen Species Amplifier for Enhanced Photodynamic Therapy.
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| Abstract |
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.
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| Authors | Dongdong Wang, Huihui Wu, Guangbao Yang, Cheng Qian, Long Gu, Hou Wang, Weiqiang Zhou, Jiawei Liu, Yinglong Wu, Xiaodong Zhang, Zhen Guo, Hongzhong Chen, Deblin Jana, Yanli Zhao |
| Journal | ACS nano (ACS Nano) Vol. 14 Issue 10 Pg. 13500-13511 (10 27 2020) ISSN: 1936-086X [Electronic] United States |
| PMID | 32910637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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