Rationally Designed Oxidase‐Mimicking Nanozymes for Correlating Drug Resistance and Cellular Senescence with Total Antioxidant Capacity

Abstract Measuring the surface antioxidant capacity of cells is critical for understanding its role in disease and for drug discovery. Herein, the developed MnO 2 @ZIF‐67 composite, featured by a core/shell architecture with MnO 2 as the core and ZIF‐67 as the shell, demonstrated remarkable oxidase‐like activity, evidenced by roughly a 26% higher maximum reaction velocity and a 46% lower K m than those of MnO 2 . The enhanced catalytic performance could be attributed to the formation of Co‐Mn bonds, which substantially reduced the energy barrier for·O 2 − generation. Utilizing MnO 2 @ZIF‐67, this work realized ultrasensitive detection of ascorbic acid, GSH, and cysteine with TMB as a substrate, offering detection limits of 912.0, 13.50, and 3.12 n m , respectively. When applied to cell analysis, the platform revealed that drug‐resistant cancer cells possessed significantly greater surface reducibility than drug‐sensitive cancer cells. Furthermore, senescent cells or tissues exhibited markedly lower antioxidant capacity. Notably, an antisenescence compound effectively restored cellular antioxidant capacity, revealing a potential inverse correlation between the extent of cellular senescence and antioxidant capacity. This study provides fundamental insights for nanozyme design and sensing applications, while also demonstrating that cell antioxidant capacity might serve as a functional indicator for assessing drug resistance and senescence degree.