Amorphous NiB@IrOx nanozymes trigger efficient apoptosis-ferroptosis hybrid therapy

The apoptosis-ferroptosis hybrid therapy opens up a new avenue for tumor eradication. Constructing ef-ficient self-cascade platform is highly desired to enhance its therapeutic effect. Herein, we report on the synthesis of novel nanozyme consist of amorphous NiB alloy completely coated with an ultrathin layer of IrOx shell (A-NiB@C-IrOx). These core-shell nanoparticles exhibited peroxidase (POD)-, catalase (CAT)-and glutathione oxidase (GSH-OXD)-like properties for inducing self-cascade catalysis. Specifically, the amorphous IrOx shell with abundant active sites can effectively convert intratumor hydrogen perox-ide (H2O2) to cytotoxic reactive oxygen species (ROS) and oxygen (O 2 ). In presence of O2, amorphous NiB core and ultrathin IrOx shell collectively catalyze the oxidation of GSH to generate H2O2, which is subsequently converted to ROS and O 2 by IrOx component. Thus, these enzymatic activities endow A-NiB@C-IrOx nanozymes with the ability of unceasing generation of ROS and O 2 and depletion of GSH. In vitro and in vivo studies demonstrate a high therapeutic efficiency of A-NiB@C-IrOx nanozymes via apoptosis-ferroptosis combination therapy.Statement of significance Apoptosis-ferroptosis hybrid therapy opens up new avenues for eradicating tumor cells. However, its ac-tual therapeutic effect is still unsatisfied. Current effort s on this hybrid therapy focus on developing ef-ficient self-cascade nanozymes to improve the efficiency of both ROS generation and GSH depletion. In this study, we constructed amorphous NiB alloy with a completed thin layer of IrOx shell (denoted as A-NiB@C-IrOx) for apoptosis-ferroptosis combination therapy. As expected, A-NiB@C-IrOx can trigger ef-ficient cascade catalytic reactions to continuously generate ROS and consume GSH, finally inducing aug-mented apoptosis-ferroptosis combination therapy.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.