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

Why It Matters

Linking antioxidant capacity to drug resistance and cellular senescence provides a novel, quantifiable biomarker that can guide therapeutic strategies and accelerate anti‑aging drug screening.

Key Takeaways

• MnO2@ZIF-67 shows 26% higher Vmax, 46% lower Km.
• Detects ascorbic acid, GSH, cysteine at sub‑nanomolar levels.
• Drug‑resistant cells exhibit elevated surface antioxidant capacity.
• Senescent cells display markedly reduced antioxidant levels.
• Antisenescence compound restores cellular antioxidant capacity.

Pulse Analysis

The MnO2@ZIF-67 nanozyme leverages a core‑shell architecture where a MnO2 core is encapsulated by a ZIF‑67 metal‑organic framework shell. The formation of Co‑Mn bonds at the interface lowers the activation energy for superoxide generation, delivering a catalytic profile that surpasses conventional MnO2 oxidases. This rational design illustrates how precise atomic‑level engineering can dramatically boost nanozyme efficiency, opening avenues for tailored catalytic materials in biomedical sensing.

Beyond its impressive kinetics, the nanozyme serves as a highly sensitive biosensing platform. By coupling the oxidase activity with the chromogenic substrate TMB, the system quantifies key intracellular antioxidants—ascorbic acid, glutathione, and cysteine—with detection limits of 912 pM, 13.5 pM, and 3.12 pM respectively. Such ultrasensitivity enables real‑time profiling of cell surface reducibility, a metric that reflects the overall antioxidant capacity of living cells without invasive extraction methods.

The ability to map antioxidant capacity has profound implications for oncology and gerontology. Elevated surface antioxidants in drug‑resistant cancer cells suggest a protective redox shield that may blunt chemotherapy efficacy, highlighting antioxidant capacity as a predictive marker for treatment response. Conversely, the sharp decline observed in senescent cells aligns with the oxidative stress theory of aging, and the reversal of this decline by an antisenescence compound underscores its potential as a therapeutic readout. Integrating this nanozyme‑based assay into drug pipelines could accelerate the identification of compounds that modulate redox balance, ultimately refining strategies against resistant tumors and age‑related degeneration.