Synthetic vectors for activating the driving axis of ferroptosis.

ABSTRACT: Ferroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIP_PCPO) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIP_PCPO is found to boost lysosomal Fe²⁺ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIP_PCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or target

SUBMITTER: Jiang J 

PROVIDER: S-EPMC11387475 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature