An artificial enzyme is a synthetic, organic molecule or ion that recreates some function of an enzyme. The area promises to deliver catalysis at rates and selectivity observed in many enzymes.
History
Enzyme catalysis of chemical reactions occur with high selectivity and rate. The substrate is activated in a small part of the enzyme's macromolecule called the active site. There, the binding of a substrate close to functional groups in the enzyme causes catalysis by so-called proximity effects. It is possible to create similar catalysts from small molecule by combining substrate-binding with catalytic functional groups. Classically artificial enzymes bind substrates using receptors such as cyclodextrin, crown ethers, and calixarene.
Artificial enzymes based on amino acids or peptides as characteristic molecular moieties have expanded the field of artificial enzymes or enzyme mimics. For instance, scaffolded histidine residues mimics certain metalloproteins and -enzymes such as hemocyanin, tyrosinase, and catechol oxidase).
Artificial enzymes have been designed from scratch via a computational strategy using Rosetta. In December 2014, it was announced that active enzymes had been produced that were made from artificial molecules which do not occur anywhere in nature. In 2016, a book chapter entitled "Artificial Enzymes: The Next Wave" was published.
Nanozymes
Nanozymes are nanomaterials with enzyme-like characteristics. They have been widely explored for various applications, such as biosensing, bioimaging, tumor diagnosis and therapy, antibiofouling.
1990s
In 1996 and 1997, Dugan et al. discovered the superoxide dismutase (SOD) mimicking activities of fullerene derivatives.
2000s
A "short review" article appeared in 2005.
It attributed the term "nanozyme"s to "analogy with the activity of
catalytic polymers (synzymes)", based on the "outstanding catalytic
efficiency of some of the functional nanoparticles synthesized". The
term was coined the previous year by Flavio Manea, Florence Bodar
Houillon, Lucia Pasquato, and Paolo Scrimin. In 2006, nanoceria (i.e., CeO2 nanoparticles)
was reported as observed, in rat experiments, preventing retinal
degeneration induced by intracellular peroxides (toxic reactive oxygen
intermediates). This was seen as indicating a possible route to an eventual treatment for causes of blindness. In 2007 intrinsic peroxidase-like activity of ferromagnetic nanoparticles was reported by Yan Xiyun
and coworkers as suggesting a wide range of applications in, for
example, medicine and environmental chemistry, and the authors reported
an immunoassay based on this property.
Hui Wei and Erkang Wang then (2008) used this mimetic property of
easily prepared magnetic nanoparticles (MNP) to demonstrate analytical
applications to bioactive molecules, describing a colorimetric assay for
hydrogen peroxide (H
2O
2) and a sensitive and selective platform for glucose detection.
2010s
As of 2016 review articles are appearing every year, in a range of journals. A book-length treatment appeared in 2015, described as providing "a broad portrait of nanozymes in the context of artificial enzyme research", and a 2016 Chinese book on "Enzyme Engineering" included a chapter on "Nanozymes".
Colorimetric applications of peroxidase mimesis in different preparations were reported in 2010 and 2011, detecting, respectively, glucose (via carboxyl‐modified graphene oxide) and single-nucleotide polymorphisms (via hemin−graphene hybrid nanosheets, and without labelling), with advantages in both cases of cost and convenience. A use of colour to visualise tumour tissues was reported in 2012, using the peroxidase mimesis of MNP coated with a protein which recognises cancer cells and binds to them.
Also in 2012, nanowires of vanadium pentoxide (vanadia, V2O5) were shown to suppress marine biofouling by mimicry of vanadium haloperoxidase, with anticipated ecological benefits. A study at a different centre two years later reported V2O5 showing mimicry of glutathione peroxidase, in in-vitro mammalian cells, suggesting future therapeutic application. The same year, 2014, it was reported that a carboxylated fullerene (C3) was neuroprotective post-injury in an in-vivo primate model of Parkinson's disease.
In 2015, a supramolecular nanodevice was proposed for bioorthogonal
regulation of a transitional-metal nanozyme, based on encapsulating
the nanozyme in a monolayer of hydrophilic gold nanoparticles,
alternatively isolating it from the cytoplasm or allowing access,
according to a gatekeeping receptor molecule controlled by competing guest species; the device is of biomimetic size and was reported as successful within the living cell, controlling pro-fluorophore and prodrug activation processes: it was suggested for imaging and therapeutic applications. A facile process for producing Cu(OH)
2 supercages was reported, and a demonstration of their intrinsic peroxidase-mimicry. A scaffolded "INAzyme" ("integrated nanozyme") arrangement was described, locating hemin (a peroxidase mimic) with glucose oxidase
(GOx) in sub-micron proximity, providing a fast and efficient enzyme
cascade reported as monitoring cerebral brain-cell glucose dynamically in vivo.
A method of ionising hydrophobe-stabilised colloid nanoparticles was
described, with confirmation of their enzyme mimicry in aqueous
dispersion.
Field trials were announced of an MNP-amplified rapid low-cost strip test for Ebola virus, in West Africa. H
2O
2
was reported as displacing label DNA, adsorbed to nanoceria, into
solution, where it fluoresces, providing a highly sensitive glucose
test. Oxidase-like nanoceria has been used for developing self-regulated bioassays. Multi-enzyme mimicking Prussian blue was developed for therapeutics. A review on MOF based enzyme mimics was published. Histidine was used to modulate iron oxide nanoparticles' peroxidase mimicking activities. Gold nanoparticles' peroxidase mimicking activities were modulated via a supramolecular strategy for cascade reactions. A molecular imprinting strategy was developed to improve the selectivity of Fe3O4 nanozymes with peroxidase-like activity. A new strategy was developed to enhance the peroxidase mimicking activity of gold nanoparticles by using hot electrons.
Researchers have designed gold nanoparticles (AuNPs) based integrative
nanozymes with both SERS and peroxidase mimicking activities for
measuring glucose and lactate in living tissues. Cytochrome c oxidase mimicking activity of Cu2O nanoparticles was modulated by receiving electrons from cytochrome c. Fe3O4 NPs were combined with glucose oxidase for tumor therapeutics. Manganese dioxide nanozymes have been used as cytoprotective shells. Mn3O4 Nanozyme for Parkinson's Disease (cellular model) was reported. Heparin elimination in live rats has been monitored with 2D MOF based peroxidase mimics and AG73 peptide.
Glucose oxidase and iron oxide nanozymes were encapsulated within
multi-compartmental hydrogels for incompatible tandem reactions. A cascade nanozyme biosensor was developed for detection of viable Enterobacter sakazakii. An integrated nanozyme of GOx@ZIF-8(NiPd) was developed for tandem catalysis. Charge-switchable nanozymes were developed. Site-selective RNA splicing nanozyme was developed. A nanozymes special issue in Progress in Biochemistry and Biophysics was published. Mn3O4 nanozymes with ROS scavenging activities have been developed for in vivo anti-inflammation. A concept entitled "A Step into the Future – Applications of Nanoparticle Enzyme Mimics" was proposed. Facet-dependent oxidase and peroxidase-like activities of Pd nanoparticles were reported. Au@Pt multibranched nanostructures as bifunctional nanozymes were developed. Ferritin coated carbon nanozymes were developed for tumor catalytic therapy. CuO nanozymes were developed to kill bacteria via a light-controlled manner. Enzymatic activity of oxygenated CNT was studied. Nanozymes were used to catalyze the oxidation of l-Tyrosine and l-Phenylalanine to dopachrome. Nanozyme as an emerging alternative to natural enzyme for biosensing and immunoassay was summarized. Standardized assay was proposed for peroxidase-like nanozymes. Semiconductor QDs as nucleases for site-selective photoinduced cleavage of DNA. 2D-MOF nanozyme-based sensor arrays was constructed for detecting phosphates and probing their enzymatic hydrolysis. N-doped carbon nanomaterials as specific peroxidase mimics were reported. Nanozyme sensor arrays were developed to detect analytes from small Molecules to proteins and cells. Copper oxide nanozyme for Parkinson's Disease was reported. Exosome-like nanozyme vesicles for tumor Imaging was developed. A comprehensive review on nanozymes was published by Chemical Society Reviews. A progress report on nanozymes was published. eg occupancy as an effective descriptor was developed for the catalytic activity of perovskite oxide-based peroxidase mimics. A Chemical Reviews on nanozymes was published. A single-atom strategy was used for developing nanozymes. Nanozyme for metal-free bioinspired cascade photocatalysis was reported. A tutorial review on nanozymes was published by Chemical Society Reviews. Cascade nanozyme reactions to convert CO2 into valuable resources was reported. Renal clearable peroxidase-like gold nanoclusters were used for in vivo disease monitoring. Copper/Carbon hybrid nanozyme was developed for antibacterial therapy. A ferritin nanozyme was developed to treat cerebral malaria. A review on nanozymes was published in Acc. Chem. Res. A new strategy called strain effect was developed to modulate the metal nanozyme activity. Prussian blue nanozymes were used to detect hydrogen sulfide (H2S) in the brains of living rats. Photolyase-like CeO2 was reported. An editorial on nanozymes "Can Nanozymes Have an Impact on Sensing?" was published.
2020s
A single-atom nanozyme was developed for sepsis management. Self-assembled single-atom nanozyme was developed for photodynamic therapy treatment of tumor. An ultrasound-switchable nanozyme against multidrug-resistant bacterial infection was reported. A nanozyme-based H2O2 homeostasis disruptor for chemodynamic tumor therapy was reported. An iridium oxide nanozyme for cascade reaction was developed for tumor therapy. A book entitled Nanozymology was published. Free radical scavenging nanosponge was engineered for ischemic stroke. A minireview on gold-conjugate based nanozymes. SnSe nanosheets as dehydrogenase mimics were developed. Carbon dot-based topoisomerase I mimic was reported to cleave DNA. Nanozyme sensor arrays were developed to detect pesticides. Bioorthogonal nanozymes were used to treat bacterial biofilms. Rhodium nanozyme was used to treat colon diseases. Fe-N-C nanozyme was developed to study drug-drug interaction. Polymeric nanozyme was developed for second near-infrared photothermal ferrotherapy. Cu5.4O nanozyme was reported for anti-inflammation therapy. CeO2@ZIF-8 nanozyme was developed to treat reperfusion-induced injury in ischemic stroke. Peroxidase-like activity of Fe3O4 was explored to study the electrocatalytic kinetics at single-molecule/single-particle level. Cu-TA nanozyme was fabricated to scavenging ROS from cigarette smoke. Metalloenzyme-like copper nanocluster was reported to have anticancer and imaging activities simultaneously. An integrated nanozyme was developed for anti-inflammation therapy. Enhanced enzyme-like catalytic activity was reported under non-equilibrium conditions for gold nanozymes. A DFT method was proposed to predict the activities of peroxidase-like nanozymes. A hydrolytic nanozyme was developed to construct an immunosensor. An orally administered nanozyme was developed for inflammatory bowel disease therapy. A ligand‐dependent activity engineering strategy was reported to develop glutathione peroxidase‐mimicking MIL‐47(V) metal–organic framework nanozyme for therapy. Single site nanozyme was developed for tumor therapy. SOD-like nanozyme was developed to regulate the mitochondria and neural cell function. Pd12 coordination cage as a photoregulated oxidase-like nanozyme was developed. An NADPH oxidase-like nanozyme was developed. A catalase-like nanozyme was developed for tumor therapy. A defect‐rich adhesive molybdenum disulfide/reduced graphene oxide nanozyme was developed for anti-bacterial. A MOF@COF nanozyme was developed for anti-bacterial. Plasmonic nanozymes were reported. Tumor microenvironment responsive nanozyme was developed for tumor therapy. A protein-engineering inspired method was developed to design highly active nanozymes. An editorial on nanozymes definition was published. A nanozyme therapy for hyperuricemia and ischemic stroke was developed. A perspective on artificial enzymes as well as nanozymes was published by Chemistry World. A review on single atom catalysts including single atom nanozymes was published. Peroxidase-like mixed-FeCo-oxide-based surface-textured nanostructures (MTex) were used for biofilm eradication. A nanozyme with better kinetics than natural peroxidase was developed. A self-protecting nanozyme was developed for Alzheimer's Disease. CuSe nanozymes was developed to treat Parkinson's Disease. A nanocluster-based nanozyme was developed. Glucose oxidase-like gold nanoparticles combined with cyclodextran were used for chiral catalysis. An artificial binuclear copper monooxygenase in a MOF was developed. A review on highly efficient design of nanozymes was published. Ni–Pt peroxidase mimics were developed for bioanalysis. A POM-based nanozyme was reported to protect cells from ROS stress. A gating strategy was used to prepare selective nanozymes. A Mn single atom nanozyme was developed for tumor therapy. A pH-responsive oxidase-like graphitic nanozyme was developed for selective killing of Helicobacter pylori. An engineered FeN3P-centred single-atom nanozyme was developed. Peroxidase- and catalase-like activity of gold nanozymes were modulated. Graphdiyne–cerium oxide nanozymes for radiotherapy of esophageal cancer. Defect engineering was used to develop nanozyme for tumor therapy. A book entitled "Nanozymes for Environmental Engineering" was published. Pd single atom nanozyme was developed for tumor therapy. A HRP-like nanozyme was developed for tumor therapy. The mechanism of GOx-like nanozyme was reported. An Account review on nanozymes was published. A mechanism study on nanonuclease-like nanozyme was reported. A perspective on nanozyme definition was published. Aptananozymes were developed. Ceria nanozyme loaded microneedles helped the hair regrowth. Catalase-like Pt nanozyme was used for small extracellular vesicles analysis. A book on Nanozymes: Advances and Applications was published by CRC Press. A review on nanozyme catalytic turnover was published. A nanozyme was developed for ratiometric molecular imaging. A Fe3O4/Ag/Bi2MoO6 photoactivatable nanozyme was developed for cancer therapy. Co/C as NADH oxidase mimic was reported. Iron oxide nanozyme was used to target biofilms causing tooth decay. A new strategey for high performance nanozyme was developed. A high-throughput computational screening strategy was developed to discover SOD-like nanozymes.
