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

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 NH₃ 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 m²/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.