Synergizing Catalysis with Post-catalysis Pseudo-Iron Release by Building Dynamic Catalytic Active Sites in Diatomic Nanozymes for Boosting Cancer Therapy

Abstract

Biomimetic nanozymes hold considerable promise for cancer therapy, but their therapeutic potential is often constrained by their limited catalytic activity. Here, we present a Ga/Zn diatomic nanozyme (Ga/Zn-NC) with a well-defined geometric structure and electronic configuration designed to emulate peroxidase and glutathione oxidase with exceptional catalytic activities, enabling cascade catalysis. We demonstrate that the formation of Ga–Zn metal bonding is essential for accelerating electron transfer and reducing the reaction energy barrier, thus enhancing the catalytic performance. Within the tumor microenvironment, the catalytic actions of Ga/Zn-NC induce oxidative damage and sensitize breast cancer cells to ferroptosis. Concurrently, the release of gallium from Ga/Zn-NC with “pseudo-iron” activity disrupts iron metabolism and activates a self-amplifying ferroptosis pathway, synergizing with the enzyme’s catalytic activity to potentiate ferroptosis and apoptosis, thereby achieving remarkable efficacy against tumors.