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 [Fe^III(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.

中文翻译：

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金属有机框架衍生的多组分纳米剂，作为增强型光动力疗法的活性氧物种放大器。

诸如谷胱甘肽（GSH）等细胞内抗氧化剂在保护恶性肿瘤细胞免受活性氧（ROS）诱导的细胞凋亡以及在多种药物和抗辐射机制中起着至关重要的作用。在本文中，我们合理设计了两种多组分自组装光动力疗法（PDT）纳米剂，即Glup-MFi-c和Glud-MFo-c，它们分别由封装在金属有机框架中的GSH钝化和GSH耗尽接头组成。与光敏剂一起对基于GSH的肿瘤PDT进行深入全面的了解。在生物相容性聚合物的保护下，多组分配位，π-π堆积以及金属离子，光敏剂和桥联键之间的静电相互作用产生了具有满意尺寸，良好胶体稳定性和超高负载能力的均质纳米粒子。^III（CN）₆ ]接头连接到肿瘤细胞中，以有效地消耗细胞内GSH，从而增强ROS的细胞杀伤效率并抑制体内肿瘤的生长。这项研究表明，Glud-MFo-c可以作为ROS放大器，为深入了解GSH在对抗癌症中的作用提供了有用的策略。