Recent research has highlighted the pivotal role of lipoxygenases in modulating ferroptosis and immune responses by catalyzing the generation of lipid peroxides. However, the limitations associated with protein enzymes, such as poor stability, low bioavailability, and high production costs, have motivated researchers to explore biomimetic materials with lipoxygenase-like activity. Here, we report the discovery of lipoxygenase-like two-dimensional (2D) MoS₂nanosheets capable of catalyzing lipid peroxidation and inducing ferroptosis. The resulting catalytic products were successfully identified using mass spectrometry and a luminescent substrate. Unlike native lipoxygenases, MoS₂ nanosheets exhibited exceptional catalytic activity at extreme pH, high temperature, high ionic strength, and organic solvent conditions. Structure–activity relationship analysis indicates that sulfur atomic vacancy sites on MoS₂ nanosheets are responsible for their catalytic activity. Furthermore, the lipoxygenase-like activity of MoS₂ nanosheets was demonstrated within mammalian cells and animal tissues, inducing distinctive ferroptotic cell death. In summary, this research introduces an alternative to lipoxygenase to regulate lipid peroxidation in cells, offering a promising avenue for ferroptosis induction.

中文翻译：

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发现诱导铁死亡的脂氧合酶样材料


最近的研究强调了脂氧合酶通过催化脂质过氧化物的产生在调节铁死亡和免疫反应中的关键作用。然而，与蛋白质酶相关的局限性，例如稳定性差、生物利用度低和生产成本高，促使研究人员探索具有脂氧合酶样活性的仿生材料。在这里，我们报道了能够催化脂质过氧化和诱导铁死亡的脂氧合酶样二维 （2D） MoS₂纳米片的发现。使用质谱法和发光底物成功鉴定了所得催化产物。与天然脂氧合酶不同，MoS₂ 纳米片在极端 pH 值、高温、高离子强度和有机溶剂条件下表现出优异的催化活性。构效关系分析表明，MoS₂ 纳米片上的硫原子空位点是其催化活性的原因。此外，MoS₂ 纳米片的脂氧合酶样活性在哺乳动物细胞和动物组织中得到证实，诱导独特的铁死亡细胞。综上所述，本研究引入了一种脂氧合酶的替代品来调节细胞中的脂质过氧化，为铁死亡诱导提供了一条有前途的途径。