A nonferrous ferroptosis-like strategy for antioxidant inhibition-synergized nanocatalytic tumor therapeutics

Ferroptosis, an emerging type of cell death found in the past decades, features specifically lipid peroxidation during the cell death process commonly by iron accumulation. Unfortunately, however, the direct delivery of iron species may trigger undesired detrimental effects such as anaphylactic reactions in normal tissues. Up to date, reports on the cellular ferroptosis by using nonferrous metal elements can be rarely found. In this work, we propose a nonferrous ferroptosis-like strategy based on hybrid CoMoO₄-phosphomolybdic acid nanosheet (CPMNS)-enabled lipid peroxide (LOOH) accumulation via accelerated Mo(V)-Mo(VI) transition, elevated GSH depletion for GPX4 enzyme deactivation, and ROS burst, for efficient ferroptosis and chemotherapy. Both in vitro and in vivo outcomes demonstrate the notable anticancer ferroptosis efficacy, suggesting the high feasibility of this CPMNS-enabled ferroptosis-like therapeutic concept. It is highly expected that such ferroptosis-like design in nanocatalytic medicine would be beneficial to future advances in the field of cancer-therapeutic regimens.