Self-Cycling Free Radical Generator from LDH-Based Nanohybrids for Ferroptosis-Enhanced Chemodynamic Therapy

Herein, a novel nanohybrid is designed by loading the PEG-encapsulated Artemisinin (denoted as A@P) on the ultrathin MgFe-LDH nanosheets (denoted as uLDHs) for improved chemodynamic therapy (CDT). The A@P/uLDHs cannot only realize the self-assembly between the Art and carrier but also be regarded as free radical generator.

A comprehensive mechanistic study suggests that this unique A@P/uLDHs is able to in situ activate Art and self-cycling generate toxic C-centered free radical inside the cancer cells, without depending on abundant H2O2, accompanied with diminished cancerous antioxidation by depleting glutathione (GSH). The accumulation ofROS and depletion ofGSH can further oxidize unsaturated fatty acid to generate lipid peroxide, whose overexpression can induce cell ferroptosis accompanied by cellular iron homeostasis turbulence.