Discovery of Lipoxygenase-Like Materials for Inducing Ferroptosis

Recent research has highlighted the pivotal role of lipoxygenases in modulating ferroptosis and immune responses through 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) MoS2 nanosheets capable of catalyzing lipid peroxidation and inducing ferroptosis. The resulting catalytic products were successfully identified using mass spectrometry and a luminescent lipoxygenase 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 its catalytic activity. Furthermore, the lipoxygenase-like activity of MoS2 nanosheets was demonstrated within mammalian cells and animal tissues, inducing a distinctive ferroptotic cell death. In summary, this research introduces an alternative of lipoxygenase to regulate lipid peroxidation in cells, offering a promising avenue for ferroptosis induction.