Recent Advances in Metal-Organic Framework-Based Nanozymes for Intelligent Microbial Biosensing: A Comprehensive Review of Biomedical and Environmental Applications

Abstract

Metal-organic framework (MOF)-based nanozymes represent a groundbreaking frontier in advanced microbial biosensing, offering unparalleled catalytic precision and structural tunability to mimic natural enzymes with superior stability and specificity. By engineering the structural features and forming composites, MOFs are precisely tailored to amplify nanozymatic activity, enabling the highly sensitive, rapid, and cost-effective detection of a broad spectrum of microbial pathogens critical to biomedical diagnostics and environmental monitoring. These advanced biosensors surpass traditional enzyme systems in robustness and reusability, integrating seamlessly with smart diagnostic platforms for real-time, on-site microbial identification. This review highlights cutting-edge developments in MOF nanozyme design, composite engineering, and signal transduction integration while addressing pivotal challenges such as biocompatibility, complex matrix interference, and scalable manufacturing. Looking ahead, the convergence of multifunctional MOF nanozymes with portable technologies and optimized in vivo performance will drive transformative breakthroughs in early disease detection, antimicrobial resistance surveillance, and environmental pathogen control, establishing a new paradigm in next-generation smart biosensing.

Keywords: biomedical; environmental; enzyme mimetics; metal–organic framework-based nanozymes; microbial biosensing; point-of-care diagnostics.

Scheme 1

Schematic overview of MOF properties and their application areas. MOF, metal–organic framework.

Figure 1

Schematic representation of CNP@bPEI-g-PEG nanozymes and their antioxidant mechanism in alleviating oxidative damage associated with dry eye disease (DED). Copyright 2022, Regenerative Biomaterials [53].

Figure 2

Diagrammatic representation of (a) the synthesis process and key characteristics of ZIF-L-Co-10 mg Cys and (b) real-time uric acid monitoring using a microreactor containing immobilized ZIF-L-Co-10 mg Cys, integrated with in vivo microdialysis and electrochemical sensing. Copyright 2021 ACS [60].

Figure 3

Overcoming pH constraints to enhance the catalytic performance of MOF-based nanozymes. Copyright 2024, Nature Communications [69].

Figure 4

Illustration of the biomimetic mineralization process involved in the growth of ZIF-8 on enzyme surfaces. 1, 2, and 3 correspond to the raw enzyme, the growth of MOF crystals on the enzyme, and the final composite material in which the enzyme is fully encapsulated by the MOF, respectively. Copyright 2021, RSC [84].

Figure 5

Depiction of the catalytic mechanism and aptasensing application employing an MOF-on-MOF nanozyme system. Copyright 2023, ACS [92].

Figure 6

Diagram outlining the main stages in the preparation of GPF-CNT@MOF electrodes and the underlying sensing mechanism. Copyright 2024, Elsevier [93].

Figure 7

Standard procedure for colorimetric detection of MDRB and associated sensing techniques. Copyright 2025, Elsevier [105].

Figure 8

(A) UV–Vis absorption spectra comparing ABTS with various catalysts: (a) ABTS alone, (b) MVCM@β-CD, (c) ZIF-67 + ABTS, (d) 2D Co-MOF + ABTS, (e) MVCM + ABTS, and (f) MVCM@β-CD + ABTS. (B) UV–Vis absorption spectra of TMB under similar conditions: (a) TMB alone, (b) MVCM@β-CD, (c) ZIF-67 + TMB, (d) 2D Co-MOF + TMB, (e) MVCM + TMB, and (f) MVCM@β-CD + TMB, all measured in NaAc-HAc buffer (pH 3.0) after 10 min at room temperature (Inset: corresponding colorimetric changes captured in photographs). Copyright 2023, Elsevier [107].

Figure 9

Illustration of the key steps involved in constructing MNPs/Zn-MOF-modified electrodes and their application in an H₂O₂ sensor for the real-time monitoring of H₂O₂ released by living cells upon drug stimulation, with data transmission to the electrochemical workstation. Copyright 2022, Elsevier [112].

Figure 10

Illustration of the HCR-multi-Apt assembly process and its application in bacterial detection. Copyright 2024, Elsevier [125].

Figure 11

(a) Bacterial culture results on agar plates following treatment with Fe-MIL-101@CMFP. (b) Quantification of bacterial colonies. (c) OD600 measurements of the filtrate over a 12 h period. (d) Comparison of sterilization efficiency across different filter paper materials. (e) Schematic illustration of the bacterial killing mechanism. Copyright 2024, Elsevier [129].

Figure 12

(a) Illustration of the synthesis procedure for the Au@ZIF-8/H composite. (b) Diagram showing its antibacterial action, stimulation of cellular activity, and promotion of skin cell and epidermal regeneration to enhance the healing of diabetic infected wounds. Copyright 2023, Elsevier [143].