Dual-Defect Engineering of LDH-Based Nanozymes to Enhance Antioxidative Effects in Ischemia Stroke-Reperfusion Injury

Advanced Functional Materials, 27 October, 2025, DOI：https://doi.org/10.1002/adfm.202517629

Dual-Defect Engineering of LDH-Based Nanozymes to Enhance Antioxidative Effects in Ischemia Stroke-Reperfusion Injury

Xiaotong Ma, Fusong Chen, Xin Liang, Rong Sun, Guannan Wang, Aihua Liu, Kelong Fan, Qiuran Xu

Abstract

Nanozymes, renowned for their antioxidant enzyme-like activities and superior stability over natural enzymes, hold great promise for treating oxidative stress-related diseases. However, their therapeutic potential remains constrained by limited catalytic efficiency and suboptimal electron transfer capabilities. To overcome these limitations, a dual-defect engineering strategy is developed to optimize the design of layered double hydroxide (LDH) nanozymes. Through Zn and Ga dual-metal doping combined with alkaline etching, E-MgZnVGa-LDH nanozymes are constructed featuring synergistic metal and oxygen vacancies. These defects significantly enhance the enzyme-like activities by optimizing the d-band center, lowering the Fermi level, and optimizing the charge distribution, thereby improving the scavenging efficiency for reactive oxygen species (ROS) and reactive nitrogen species (RNS). Compared with MgV-LDH, E-MgZnVGa-LDH exhibits superior antioxidant efficacy. In vivo, these nanozymes effectively mitigate oxidative stress-induced brain damage, reduce astrocyte activation, and suppress downstream inflammation in a stroke reperfusion model. This study highlights the critical role of vacancy defects in regulating nanozyme activity and establishes a framework for the rational design of high-performance nanozymes for oxidative stress-related therapies.

文章链接：https://advanced.onlinelibrary.wiley.com/doi/10.1002/adfm.202517629