NIR-II-Accelerated 2D-on-2D Silicene/MOF Heterointerfaces Disrupt Tumor Redox Homeostasis for Targeted Ferroptosis

Abstract

Catalytic ferroptosis therapy provides an attractive approach for tumor treatment, but its practical efficacy is often limited by insufficient reaction kinetics and the strong redox buffering capacity of the tumor microenvironment. Herein, we report an interface-engineered 2D-on-2D catalytic nanoplatform, SNs/FTC@Apt-P (SFTCP), constructed by integrating silicene nanosheets with an ultrathin Fe−Cu metal−organic framework and further functionalized with a PD-L1 aptamer for tumor targeting. The silicene/Fe−Cu metal−organic framework heterointerface offers abundant exposed catalytic sites and facilitates interfacial electron transfer, improving Fenton-like catalytic activity under biologically relevant conditions. At the biointerface, Fe3+/Cu2+ bimetallic centers consume intracellular glutathione (GSH) and weaken the xCT/GSH/GPX4 antioxidant defense pathway, thereby reducing the ability of tumor cells to eliminate lipid peroxides. Under NIR-II irradiation, SFTCP generates localized photothermal stimulation that acts as an external kinetic accelerator to further enhance catalytic oxidative stress. This interface-mediated and photothermally amplified process promotes lipid peroxide accumulation and induces ferroptotic tumor cell death. In vivo, aptamer-mediated targeting combined with NIR−II−augmented catalysis increases intratumoral lipid peroxidation and achieves 87% tumor growth inhibition with favorable biosafety. This work demonstrates an applied interface-engineering strategy for constructing catalytic nanomaterials that integrate redox regulation, photothermal activation, and ferroptosis-based tumor therapy.