Discovery\nof Lipoxygenase-Like Materials for Inducing\nFerroptosis

Recent research has highlighted the\npivotal role of lipoxygenases\nin modulating ferroptosis and immune responses by catalyzing the generation\nof lipid peroxides. However, the limitations associated with protein\nenzymes, such as poor stability, low bioavailability, and high production\ncosts, have motivated researchers to explore biomimetic materials\nwith lipoxygenase-like activity. Here, we report the discovery of\nlipoxygenase-like two-dimensional (2D) MoS<sub>2</sub>nanosheets capable\nof catalyzing lipid peroxidation and inducing ferroptosis. The resulting\ncatalytic products were successfully identified using mass spectrometry\nand a luminescent substrate. Unlike native lipoxygenases, MoS<sub>2</sub> nanosheets exhibited exceptional catalytic activity at extreme\npH, high temperature, high ionic strength, and organic solvent conditions.\nStructure–activity relationship analysis indicates that sulfur\natomic vacancy sites on MoS<sub>2</sub> nanosheets are responsible\nfor their catalytic activity. Furthermore, the lipoxygenase-like activity\nof MoS<sub>2</sub> nanosheets was demonstrated within mammalian cells\nand animal tissues, inducing distinctive ferroptotic cell death. In\nsummary, this research introduces an alternative to lipoxygenase to\nregulate lipid peroxidation in cells, offering a promising avenue\nfor ferroptosis induction.