Artificial enzyme
It seeks to deliver catalysis at rates and selectivity observed in naturally occurring enzymes.
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 molecules by combining substrate-binding with catalytic functional groups.
Classically, artificial enzymes bind substrates using receptors such as cyclodextrin, crown ethers, and calixarene.
For instance, scaffolded histidine residues mimic certain metalloproteins and enzymes such as hemocyanin, tyrosinase, and catechol oxidase.
[13][14] The term "nanozyme" was coined in 2004 by Flavio Manea, Florence Bodar Houillon, Lucia Pasquato, and Paolo Scrimin.
In 2006, nanoceria (CeO2 nanoparticles) was reported to prevent retinal degeneration induced by intracellular peroxides (toxic reactive oxygen intermediates) in rat.
[18] 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 designed an immunoassay based on this property.
[19][20] Hui Wei and Erkang Wang then (2008) used this property of easily prepared magnetic nanoparticles to demonstrate analytical applications to bioactive molecules, describing a colorimetric assay for hydrogen peroxide (H2O2) and a sensitive and selective platform for glucose detection.
[36] Colorimetric applications of peroxidase mimesis in different preparations were reported in 2010 and 2011, detecting, respectively, glucose (via carboxyl-modified graphene oxide)[37] and single-nucleotide polymorphisms (in a label-free method relying on hemin−graphene hybrid nanosheets),[38] with advantages in both cost and convenience.
A use of colour to visualise tumour tissues was reported in 2012, using the peroxidase mimesis of magnetic nanoparticles coated with a protein that recognises cancer cells and binds to them.
[40] A study at a different centre two years later reported V2O5 showing mimicry of glutathione peroxidase in vitro in mammalian cells, suggesting future therapeutic application.
[41] The same year, a carboxylated fullerene dubbed C3 was reported to be neuroprotective in a primate model of Parkinson's disease.
[42] 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, alternately isolating it from the cytoplasm or allowing access according to a gatekeeping receptor molecule controlled by competing guest species; the device, aimed at imaging and therapeutic applications, is of biomimetic size and was successful within the living cell, controlling pro-fluorophore and prodrug activation.
[43][44] An easy means of producing Cu(OH)2 supercages was reported, along with a demonstration of their intrinsic peroxidase mimicry.
[45] 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.
[46] A method of ionising hydrophobe-stabilised colloid nanoparticles was described, with confirmation of their enzyme mimicry in aqueous dispersion.
[47] De novo designed metallopeptides with self-assembling properties carry out the oxidation reaction of dimethoxyphenol.
[48] Field trials in West Africa were announced of a magnetic nanoparticle–amplified rapid low-cost strip test for Ebola virus.
[49][50] H2O2 was reported as displacing label DNA, adsorbed to nanoceria, into solution, where it fluoresces, providing a highly sensitive glucose test.
[58] Researchers designed gold nanoparticle–based integrative nanozymes with both surface-enhanced Raman scattering and peroxidase-mimicking activities for measuring glucose and lactate in living tissues.
[63] Heparin elimination in live rats was monitored with two-dimensional MOF-based peroxidase mimics and AG73 peptide.
[64] Glucose oxidase and iron oxide nanozymes were encapsulated within multi-compartmental hydrogels for incompatible tandem reactions.
[70] Mn3O4 nanozymes with the ability to scavenge reactive oxygen species were developed and showed in vivo anti-inflammatory activity.
[71] A proposal entitled "A Step into the Future – Applications of Nanoparticle Enzyme Mimics" was presented.
[81] Two-dimensional MOF nanozyme-based sensor arrays were constructed for detecting phosphates and probing their enzymatic hydrolysis.
[83] Nanozyme sensor arrays were developed to detect analytes from small molecules to proteins and cells.
[129] A ligand-dependent activity engineering strategy was reported to develop a glutathione peroxidase–mimicking MIL-47(V) metal–organic framework nanozyme for therapy.
[186] Combined with small interfering RNA, ceria nanozyme was used for synergistic treatment of neurodegenerative diseases.
[227] Certain nanozymes have the potential for treating ischemic stroke and traumatic brain injury due to their ability to mitigate the harmful effects of excessive free radical production, oxidative brain damage, inflammation, and blood-brain barrier disruption.
