铁过氧化物死亡是一种非凋亡形式的调控性细胞死亡。肿瘤微环境中过量表达谷胱甘肽 (GSH) 和过氧化氢 (H2O2) 产生不足限制了铁过氧化物死亡的效率。在本研究中，通过在均匀的以鞣醇茶多酚 (EGCG) 与 Fe3+ 包覆的金属-有机骨架 (Ce-aMOFs) 表面开发了称为 MEFs 的治疗诊断纳米粒子。Fe3+ 被 EGCG 中相邻的酚羟基团螯合。在肿瘤细胞内部，过量表达的 GSH 和弱酸性介质会降解包覆物，释放 Fe3+ 和 EGCG，并使 Ce-aMOFs 暴露。Fe3+ 和 EGCG 会消耗 GSH，同时将 Fe3+ 转化为 Fe2+。Ce-aMOFs 具有超氧化物歧化酶 (SOD)-和磷酸酶样活性的纳米酶活性。在肿瘤微环境中，Ce-aMOFs能催化内源性超氧阴离子 (O2˙-) 转化为 H2O2，而 Fe2+ 能催化 H2O2 生成有毒的羟基自由基 (˙OH)，这可能通过铁过氧化物死亡进一步诱导肿瘤细胞死亡。此外，Ce-aMOFs 的磷酸酶样活性可以可持续地去磷酸化 NADPH，有效抑制细胞内 GSH 的生物合成。因此，MEFs 确保降低细胞内 GSH 水平并提高氧化压力，增强铁过氧化物死亡效应。

Ferroptosis is a non-apoptotic form of regulated cell death. The efficiency of ferroptosis is restrained in the tumor microenvironment (TME) by overexpression of glutathione (GSH) and insufficient production of hydrogen peroxide (H2O2). In this work, theranostic nanoparticles Ce-aMOFs@Fe3+-EGCG, termed MEFs, are developed by coating uniform Ce-based amorphous metal-organic frameworks (Ce-aMOFs) with epigallocatechin gallate (EGCG) and Fe3+. Fe3+ is chelated by the adjacent phenol hydroxyl groups in EGCG. In the tumor cell interior, overexpressed GSH and weak acidic medium degrade the coating to release Fe3+ and EGCG accompanied by exposure of Ce-aMOFs. Fe3+ and EGCG consume GSH along with turning Fe3+ into Fe2+. Ce-aMOFs act as a nanozyme possessing dual-enzymatic activities, i.e. superoxide dismutase (SOD)- and phosphatase-like activities. In the TME, Ce-aMOFs catalyze the conversion of endogenous superoxide (O2˙-) into H2O2, and Fe2+ catalyzes H2O2 to generate toxic hydroxyl radicals (˙OH), which may further induce tumor cell death through ferroptosis. In addition, the phosphatase-like activity of Ce-aMOFs may sustainably dephosphorylate NADPH and effectively inhibit intracellular biosynthesis of GSH. Therefore, MEFs ensure down-regulation of intracellular GSH levels and up-regulation of oxidative pressure, which enhance the ferroptosis effect.