Nanozymes in Action: Inbuilt Asymmetric Local Electric Field for Enhanced Ferroptosis-Pyroptosis Therapy.

Conventional nanozymes are generally reported to have a symmetric coordination environment near the active centers that can hinder electron transfer and result in limited catalytic efficiency. In a recent article by Na Na and colleagues, an axial sulfur-bridged Mo-S-Cu (A-CuN3S1@MoS2-x) nanozyme is developed that functions by utilizing an expanded asymmetric local electric field (LEF). The innovative structure significantly ramps up multienzymatic activities, which include catalase-, peroxidase-, and oxidase-like functions, while concomitantly depleting glutathione. As this nanozyme specifically targets mitochondria in tumors, it initiates a cascade of reactive oxygen species (ROS), activating combined ferroptosis and gasdermin E (GSDME)-mediated pyroptosis. We highlight these findings on how the axial-bridging strategy offers a sophisticated design for nonapoptotic tumor therapy through the modalities of coordination chemistry and electronic structure modulation.