Nanozymes
The discovery of nanozymes originated from a chance scientific experiment in 2007. In order to apply nanotechnology in biomedicine, Yan's research group combined antibodies labeled with horseradish peroxidase with iron oxide nanoparticles to achieve magnetic enrichment detection of antigens. Due to the horseradish peroxidase linked to the antibody, the substrate could be colorized. However, the researchers found during the experiment that the iron oxide nanoparticles alone could also achieve colorization of the substrate, which puzzled them. In order to further study this phenomenon, different researchers of Yan's research group conducted repeated verifications, eliminating all possible factors that could affect the experimental results, and ultimately found that iron oxide nanoparticles indeed possessed properties similar to horseradish peroxidase, thus discovering the existence of nanozymes. Since the first discovery of nanozymes in 2007, more than 300 types of nanomaterials with enzymatic activity have been found, such as Fe3O4, CuO, V2O5, MnFeO3, graphene quantum dots, CeO2, BiFeO3, CoFe2O4, MnO2, etc.
Fig.1 Schematic illustration of exosome-like nanozyme vesicles for the H2O2-responsive catalytic photoacoustic imaging of tumors (Ding et al., 2018).
Why do Nanozymes Have Intrinsic Enzyme-Like Catalytic Activity?
Countless theoretical hypotheses have emerged in an attempt to unravel the intricate molecular workings of nanozymes. A glaring disparity between nanomaterials and macroscopic substances lies in their size, an aspect that holds immense importance. Diminishing the size of particles enhances their specific surface area, meaning that for nanoparticles of equal mass, a smaller individual particle equates to a larger overall surface area. The catalytic reactions orchestrated by nanozymes predominantly occur on their surfaces, thus underscoring the significance of size reduction. The smaller the size, the more expansive the surface area of the nanozyme, fostering heightened opportunities for contact between particles and substrates, ultimately amplifying catalytic activity. Remarkably, when the nanozyme's dimensions are sufficiently diminished, the catalytic prowess of a single atom can be aptly unleashed. This bears an uncanny resemblance to biological enzymes, bearing in mind that many biological enzymes frequently harbor a metal ion at their active core.
Nanozymes for Pathological Disease Diagnosis
Peroxidase nanozymes catalyze the oxidation of colorimetric substrates (such as 3,3,5,5-tetramethylbenzidine (TMB), diaminobenzidine (DAB), and o-phenylenediamine (OPD)), producing a color reaction that can be used for imaging and identification of biomarkers in tissue sections for pathological diagnosis. Research has found that magnetic iron protein nanoenzymes (M-HFn) can be used for tumor targeting and imaging. HFn nanocages specifically recognize tumor cells by binding to transferrin receptor 1 (TfR1) overexpressed in tumor cells. So far, various staining methods based on peroxidase nanozymes have been developed for the pathological diagnosis of breast cancer, colorectal cancer, gastric cancer, pancreatic cancer, hepatocellular carcinoma, esophageal cancer, bladder cancer, etc. In addition to tumor pathological diagnosis, peroxidase nanozymes are also used for pathological identification of human high-risk ruptured atherosclerotic plaques.
Nanozymes for Live Cell and Organelle Imaging
The most commonly used cytological detection methods currently are flow cytometry, cytological smears, and nucleic acid testing. These traditional methods are characterized by high technical requirements, time-consuming processes, or high costs. Nanozyme-driven colorimetric reactions can be used for qualitative and quantitative analysis of cytological features.
Researchers have utilized the catalytic activity of nanozymes to design real-time detection probes for live cell organelle imaging. In addition to organelle imaging detection, there are several other nanozyme-based colorimetric methods used for specific disease imaging, including jaundice, acquired immune deficiency syndrome, diabetes, infectious diseases, and neurodegenerative diseases.
Nanozymes for In Vivo Imaging
By utilizing the unique physicochemical properties of nanozymes, such as fluorescence, electrochemical, and paramagnetic properties, nanozymes have been extensively developed for in vivo monitoring and imaging of diseases. For example, after utilizing the peroxidase-like activity of iron nanozymes and the peroxidase-like activity of single-dose iron nanozymes to achieve ex vivo tumor tissue imaging, researchers used the unique r2 relaxation property of iron nanozymes to achieve in vivo magnetic resonance imaging (MRI) of tumors. Besides cancer, nanozymes are also widely applied in imaging many other diseases, such as infections, inflammation, and some neurological disorders.
The emergence of nanozymes reveals the biological effects of inorganic nanomaterials. Nanozymes can serve as substitutes for natural enzymes because they can address the limitations of natural enzymes such as low stability, high cost, and difficult storage.
References
- Ding H.; et al. Exosome-like nanozyme vesicles for H2O2-responsive catalytic photoacoustic imaging of xenograft nasopharyngeal carcinoma. Nano Letters. 2018, 19(1): 203-9.
- Liang M.; Yan X. Nanozymes: from new concepts, mechanisms, and standards to applications. Accounts of Chemical Research. 2019, 52(8): 2190-200.
- Wang P.; et al. Nanozymes: a new disease imaging strategy. Frontiers in Bioengineering and Biotechnology. 2020, 8: 15.
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