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Progress in Chemistry 2023, Vol. 35 Issue (9): 1389-1398 DOI: 10.7536/PC230113 Previous Articles   Next Articles

• Review •

Metal-Organic Framework-Based Nanozymes for Clinical Applications

Wenhao Luo1,2, Rui Yuan1,2, Jinyuan Sun1,2, Lianqun Zhou3, Xiaohe Luo1,4(), Yang Luo1,5()   

  1. 1 School of Medicine, Chongqing University,Chongqing 400044, China
    2 College of Bioengineering, Chongqing University,Chongqing 400044, China
    3 Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences,Suzhou 215163, China
    4 Chongqing University Three Gorges Hospital,Chongqing 400044, China
    5 College of Life Science and Laboratory Medicine, Kunming Medical University,Kunming 650050, China
  • Received: Revised: Online: Published:
  • Contact: *e-mail: Luoy@cqu.edu.cn(Yang Luo); xiaoheluo@163.com(Xiaohe Luo)
  • Supported by:
    The National Key Research and Development Program of China(2022YFC2009600); The National Key Research and Development Program of China(2022YFC2009603); The National Science Fund for Distinguished Young Scholars(82125022); The National Natural Science Foundation of China(82202633); The National Natural Science Foundation of China(82072383); The Chongqing Higher Education Teaching Reform Research Project(213035)
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Enzymes are considered as natural biocatalysts, which catalyze many biochemical reactions with good catalytic efficiency, biocompatibility, and substrate specificity. The intrinsic limitations of natural enzymes such as low stability, high cost, and storage difficulty have led to the introduction of artificial enzymes that imitate the activity of natural enzymes. With the rapid development of nanomaterials in the recent decade, novel enzyme-mimicking nanomaterials (nanozymes) have attracted considerable attention from researchers. Nanozymes are defined as a class of artificial nanomaterials possessing intrinsic enzymes-like activities, which have the advantages of simple preparation processes, low cost and some environmental tolerance. However, most of them are limited by their low activity and relatively poor stability, leading to many difficulties in the application of biochemical analysis. Among them, metal-organic framework nanozymes (MOFs) have demonstrated a wide range of uses because of their evident favorable circumstances, including the large surface area and porosity for functionalization, uniform active sites, high catalytic activity and stability, simple and controllable synthesis and low cost. In this review, we provide a summary of the clinical detection application of MOFs in nucleic acid, protein and small molecules based on their different activity classification (peroxidase, oxidase, catalase, superoxide dismutase, and hydrolase). Finally, we look forward to the opportunities and challenges that MOFs will face in clinical detection, promoting their clinical application transformation.

Contents

1 Introduction

2 Classification of MOF nanozymes

2.1 Peroxidase

2.2 Oxidase

2.3 Catalase

2.4 Superoxide dismutase

2.5 Hydrolase

3 Application of MOF nanozymes in clinical detection

3.1 Application of MOF nanozymes in nucleic acid detection

3.2 Application of MOF nanozymes in protein detection

3.3 Application of MOF nanozymes in the detection of small molecule

4 Conclusion and outlook

4.1 Strengthening environmental stability

4.2 Enhancing substrate specificity

4.3 Enhancing the enzymes-like catalytic activity

Key words: clinical tests, metal-organic framework, nanozymes, nucleic acids testing, protein analysis
Table 1 The main classification of MOF nanozymes[8,11???????????? ~24]
Classification Advantages Disadvantages Reaction principle Examples ref
Peroxidase Higher catalytic activity than natural peroxidase, and adjusted active sites The high activity is only in weak acidity condition (pH is about 4). Fenton-like reaction Zr-MOF,Fe-MOF,
Ni-MOF		 8,11,12
Oxidase Higher catalytic activity than natural oxidase, and H2O2 is not required for the reaction The selectivity and specificity of substrate are insufficient in
complex samples		 Activating O2 to
produce ROS		 some Ce-MOF,Co-MOF,Cu-MOF 13⇓⇓~16
Catalase High stability, adjustable enzyme activity, simple preparation, good biocompatibility The high catalytic activity is only at specific pH. Accelerating the
dismutation of H2O2 into water and oxygen		 Ce-MOF,Mn-MOF 17⇓~19
Superoxide dismutase Higher stability than natural superoxide dismutase, and high catalytic activity Certain cytotoxicity Disproportionation of
superoxide anion to oxygen and hydrogen peroxide		 Cu/Zr-MOF,Sn-MOF 8,20,21
Hydrolase Higher stability than natural hydrolase, wide range of applications, and flexible design The activity of catalyst is easily affected by strong acid and alkali The hydrolysis of the metal nodes and
coordination structures		 Zr-MOF,Ce-MOF 8,22⇓~24
Fig.1 Application of MOF nanozymes in nucleic acid detection.(A)ZIF-8 nanozymes triggered cascade catalytic reaction for miRNA-21 detection[54];(B)MOF cascade nucleic acid circuit for circulating miRNA analyzing in serum[57];(C)multifunctional iron-based metal-organic framework (PdNPs@Fe-MOFs) for miRNA-122 identification[58];(D)MOF nanozymes assisted homogeneous electrochemical system for miRNA discrimination[59]
Fig.2 Application of MOF nanozymes in protein detection. (A)peroxidase mimic Fe-MIL-88A for thrombin detection[62];(B)MOF-818 synthesized with the surface of carbon cloth fiber for the identification of thrombin[63];(C)Peroxidase mimic two-dimensional MOF for Alkaline Phosphatase determination[68];(D)MIL53 (Fe) / G4-hemin for the discrimination of alkaline phosphatase[69]
Fig.3 Application of MOF nanozymes in the Detection of small molecules.(A)Fe-MOF-Gox cascade catalysis for glucose detection[74];(B)MOF nanozymes for the detection of glucose and Cysteine[75];(C)MOF nanozymes for the Determination of aflatoxin B1 in ELISA[78];(D)Hemin@BSA@ZIF-8 for H2O2 and bisphenol Aidentification[81]
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