Leavening Inspired Synthesis of Mesoporous High‐Entropy Oxide Nanozymes for Detection and Discrimination of Multiple Biological Antioxidants

ABSTRACT High‐entropy oxides (HEOs) with mesoporous framework and high enzyme‐like catalytic properties hold great promise for biomedical applications. However, the synthesis of mesoporous HEO nanozymes remains challenging due to mesopore collapse during crystallization process. Herein, a leavening inspired synthesis strategy is proposed to fabricate a family of mesoporous HEO nanozymes. Glucose and urea produce a large amount of NH ₃ under calcination, causing the precursor to expand and carbonize rapidly. The carbon supports the crystallization of the mesoporous framework and prevents it from collapsing. This method is universal for preparing a variety of mesoporous HEO nanozymes. Different kinds of mesoporous HEOs, including spinel‐, fluorite‐, and bixbyite‐type with large pore sizes (8–12 nm), high specific surface area (up to 63.2 m ² /g), and well‐crystallized frameworks are synthesized, exhibiting oxidase (OXD)‐like activities. Leveraging oxidase‐like activity, a four‐channel colorimetric sensing array is constructed for simultaneous detection and discrimination of five key serum antioxidants: ascorbic acid, glutathione, L‐cysteine, uric acid, and tocopherol with range from 10 to 50 µmol/L. The Support Vector Machine algorithm is used, and the accuracy rate reaches 92%. This work provides a universal synthesis strategy for mesoporous HEO nanozymes with tunable compositions and excellent OXD‐like activities, showing great potential in complex bioanalytical applications.