Reactive Oxygen Species-Induced Aggregation of Nanozymes for Neuron Injury

Nanozymes show excellent enzyme activity and robust catalytic properties, but the targeting capability to disease organs is limited because of lack of specificity. Herein, we developed an ultrasmall (∼3 nm) organic nanozyme that can gradually aggregate under a reactive oxygen species (ROS)-rich environment via a spontaneous reaction, namely, ROS-induced aggregation. The size of nanozymes is 75 and 100 times higher than the original size under ^•OH and H₂O₂ environments without losing enzyme activity. In vitro experiments confirm that nanozymes prefer to aggregate in mitochondria under ROS-rich conditions. Importantly, the nanozymes show in situ ROS-induced aggregation in the brain, ∼9 times higher uptake than ordinary nanozymes, indicating their potential for treating ROS-related diseases in the central nervous system.