A Review on Multi-Enzyme Activity of ZIF, PBA, PCN and MIL MOF-Derived Cascade Nano-Enzymes for Catalytic Applications

Abstract

Metal-organic frameworks (MOFs) with multiple enzyme-like activities termed multienzyme mimetic catalysts have emerged as powerful candidates for diverse catalytic applications, particularly in biosensing and biomedicine. Unlike single-enzyme nanozymes, these multienzyme MOF-based catalysts offer enhanced catalytic efficiency through synergistic effects, cascade reactions, and dynamic responsiveness to environmental stimuli. Among them, four classes zeolitic imidazolate frameworks (ZIFs), porous coordination networks (PCNs), Prussian blue analogs (PBAs), and Materials of Institut Lavoisier (MILs) have shown exceptional promise due to their structural tunability and catalytic versatility. This review provides a comprehensive overview of multienzyme-like activity in these MOFs, including advances in metal doping, biomolecule incorporation, MOF-on-MOF architectures, carbonization strategies, and MOF-derived nanozymes. We explore the underlying catalytic mechanisms and discuss recent strategies to modulate and enhance their enzyme-mimicking behavior. Special emphasis is placed on applications in sensing and therapy, including toxic metal, gas, and biomolecule detection, antibacterial activity, wound healing, tumor therapy, photothermal treatment, chemotherapy, and reactive oxygen species/ reactive nitrogen species (ROS/RNS) scavenging. A critical analysis reveals that while ZIF, PCN, PBA, and MIL-based MOFs show great promise, most studies remain at proof-of-concept with limited clinical translation. It provides a unified perspective to guide the rational design and implementation of multienzyme MOFs in next-generation biomedical and sensing technologies.