Artificial Cells, Nanomedicine, and Biotechnology

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Nanozyme applications in biology and medicine:

an overview

Jafar Golchin, Kazem Golchin, Neda Alidadian, Shahrooz Ghaderi, Sajjad

Eslamkhah, Masoud Eslamkhah & Abolfazl Akbarzadeh

To cite this article: Jafar Golchin, Kazem Golchin, Neda Alidadian, Shahrooz Ghaderi, Sajjad
Eslamkhah, Masoud Eslamkhah & Abolfazl Akbarzadeh (2017) Nanozyme applications in biology
and medicine: an overview, Artificial Cells, Nanomedicine, and Biotechnology, 45:6, 1069-1076,
DOI: 10.1080/21691401.2017.1313268

To link to this article: https://doi.org/10.1080/21691401.2017.1313268

Published online: 21 Apr 2017.

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ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY, 2017
VOL. 45, NO. 6, 1069–1076
http://dx.doi.org/10.1080/21691401.2017.1313268

Nanozyme applications in biology and medicine: an overview

Jafar Golchina, Kazem Golchina, Neda Alidadianb, Shahrooz Ghaderib,c, Sajjad Eslamkhahb, Masoud Eslamkhahb
and Abolfazl Akbarzadehd
a
Division of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; bImmunology Research Center, Tabriz University of Medical Sciences,
Tabriz, Iran; cDivision of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;
d
Division of Nanomedicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

ABSTRACT ARTICLE HISTORY

Nanozymes, in nature, are artificial enzymes. Innovated by Ronald Breslow to mimic enzymes. Received 16 January 2017
Nanozymes have widespread applications including targeted cancer therapy, diagnostic medicine and Accepted 27 March 2017
bio-sensing even environmental toxicology. However, these applications are a novel research field in
biomedicine, but are growing fast. Enzyme-based applications such as immune-absorbent assay (ELIZA)
KEYWORDS
are expensive because of the complexity of producing enzymes and antibodies. Not only, some nano- Nanozyme; metal
particles can mimic these enzymes such as superoxides, but also they can manipulate biological path- nanoparticles; bio-mimic;
ways directly like autophagy. These abilities make them a suitable alternative for both therapy and medical application
diagnosis. In this review, we opted on metal nanoparticles and application of this cutting edged tech-
nology into modern medicine.

Introduction Although hydrogen peroxide itself is stable and less active,

Nanomaterials performance as enzymes
Natural enzymes are mostly proteins, made from amino acid
sequence and have a different structure. However, most
Nanomaterials have different size or structure [1]. Although,
proteins are considered as soft materials, nanomaterial is
hard with a porphyritic nucleus [2]. Notably, they share a cer-
tain likeness, such as overall size, shape and surface charge,
which enable nanomaterials to mimic enzyme [3]. In this part,
we will look at different nanomaterial that can mimic natural
enzymes as the base of texture similarity and flexibility.
Cerium oxide-based nanomaterial
Cerium oxide nanoparticles and magnetic nanoparticles are
the most widely used metal oxide. CeO2 nanoparticles, (Ce3þ,
Ce4þ), possess many unique properties that have proven in
biomedical and catalytic applications. Nanoceria mimics SOD
thanks to catalyzing the dismutation of superoxide anions
into hydrogen peroxide and molecular oxygen (2O2 þ 2 Hþ
!H2O2þO2) [1,4]. SOD have an antioxidant ability leading to
many biological applications. Some alternative role exists for
cerias as SOD (O2þCe4þ!O2þ Ce3þ and O2þCe3þþH2þ!
H2O2þCe4þ). Nanoceria mimics catalase and catalase the
decomposition of hydrogen peroxide into molecular oxygen
and water (2H2O2!2H2O þ O2). Hydrogen peroxide, end
product of superoxide radicals’ dismutation (2O2 þ 2 Hþ !
H2O2þO2), plays a dual role in biological systems. It may be a
signalling molecule or a non-radical reactive oxygen species.
but may convert into highly active and detrimental hydroxyl
radical through Fenton chemistry. In nature, catalase
employed as the most efficient enzyme for the conversion of
hydrogen peroxide to less active oxygen. Some studies
showed catalase-like activity and SOD-like activity depend on
Ce3þ/Ce4þ ratio. Oxidase reaction including of oxidizing a
substrate by molecular oxygen late, converted into either
water or hydrogen peroxide. (AredþO2þH2O!AoxþH2O2 and
AredþO2!AoxþH2O and Aredþ O2!AoxþO2). Cerium oxide-
based nano materials cerium oxide (ceria) identified as highly
catalytic performance in various applications. Thanks to the
presence of mixed volume states of Ce3þ and Ce4þ, and oxy-
gen vacancies [5]. Cerium (III) nitrate reduces superoxide lead-
ing to superoxide oxidase (SOD) mimetic [6]. The initial
studies demonstrated that vacancy-engineered nanoceria pro-
tected of normal cells from radiation-induced damage but
not tumour cells [7]. The protective role of the nanoceria is
related to omission of radiation-induced free radicals, which
is may be to occur through oxidation process via a Ce3þ to
Ce4þ conversion [8]. Nanoceria and enzyme including (SOD,
catalase, oxidase) share their properties to some biomedical
functions such as omission radicals both in vitro and in vivo
[9–12]. For instance, nanoceria introduced as a novel super-
oxide dismutase (SOD), catalase and oxidase mimetic proper-
ties [13]. Recently, revealed that there is a significant
similarity between SOD and nanoceria by competitive elec-
tron paramagnetic resonance (EPR) analysis [14]. According to
the evidence, nanoceria exhibit superoxide dismutase (SOD)
activity by using a ferricytochrome [15]. Nanoceria showed

CONTACT Abolfaz Akbarzadeh akbarzadehab@tbzmed.ac.ir Division of Nanomedicine, Faculty of Advanced Medical Sciences, Tabriz, Iran
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
1070 J. GOLCHIN ET AL.
antioxidant activity by catalyzing dismutation reaction of
superoxide anions into hydrogen peroxide and molecular
oxygen [16]. Nanoceria is ROS scavenger and mimics the
chemical reactions and antioxidant properties of SOD [17].
However, we do not know yet what physical characteristics
exactly, make nanoceria effective at scavenging superoxide
anion [18]. Although, some studies suggest that the surface
of nanoceria oxidation state plays a perfect role in the SOD
mimetic. The ability to scavenge superoxide related to cerium
(III) concentrations at the surface particle [19]. On the other
hand, SOD plays important role in redox biology and cellular
Anti-inflammatory response [20]. Free radicals overproduction
such as nitric oxide (NO) by the enzyme inducible nitric oxide
synthase (iNOS) is critical to regulate inflammation. NO over-
production leads to some disease and collaborates to tissue
destruction, consequently [21]. The ability of nanoceria to
scavenge free radical or reactive oxygen species (ROS) and
inhibit inflammatory mediator helps to protect the whole cel-
lular architecture against inflammatory disease. Also, it has a
potential to manage chronic inflammation conditions thanks
to reducing ROS production [22]. In parallel, superoxide dis-
mutase (SOD) enzymes are required for antioxidant defenses,
maintaining the steady-state levels of O2; surprisingly, nano-
ceria are remarkably efficacious in reducing the inflammation
both in vitro and in vivo [23]. SOD have anti-apoptotic prop-
erties although the signalling pathway of this anti-apoptosis
mechanism is not clear, but maybe related to Ce3þ/
Ce4þ redox reactions [24]. Some studies demonstrated that
SOD is neuroprotective. In a neurodegenerative disease like
Alzheimer, free radicals play an important role [25]. Using a
mouse hippocampal brain slice model of cerebral ischemia,
showed that ceria nanoparticles reduce ischemic cell death
50%. These findings proposed that the scavenging proper-
ties of nanoceria to eliminate peroxynitrite. It must be
answered, in which mechanism cerium oxide nanoparticles
mitigate ischemic brain injury. Peroxynitrite plays a pivotal
role in the dissemination of oxidative injury in biological tis-
sues [26]. There is another application of nanoceria-based
enzymes such as promotion of stem cell growth. For
example, Xiang et al. showed that nanoceria increased vascu-
larization of bone grafts by activating calcium channel
through mesenchymal stem cells. [27]. Also, they used cerium
oxide nanoparticle as a modified scaffold to improve the
blood vessel distribution inside of tissue engineering bone.
Because of the unique properties of cerium oxide nanopar-
ticles such as power to proliferate stem cells [28]. It may be
used as scaffold/artificial niche. However, ceria-nanoparticles
produced as therapeutic agents in some inflammatory dis-
ease, they have wide range applications in diagnostics medi-
cine [29]. For example, ceria nanoparticle as oxidase mimic
use in the detection of glucose in serum or urea. This method
is based on the changes in the physicochemical properties of
ceria, as chromogenic indicators, in response to the analyte.
Another application of nanoceria is Immunoassay technique
thanks to HRP enzyme sensing. Thus, the conjugate nanoceria
detect cancer cells [30]. Ceria oxide nanoparticle has a unique
application in environmental toxicology for an instant: nano-
ceria deleted pollutants by oxidation of CO and hydrocarbon
from automobile engine lightening [31,32].
Iron oxide-based nanomaterial
Peroxidase, consisting of a large family of enzymes, catalyzes
the oxidation of its substrate with peroxide (hydrogen perox-
ide in most cases) (AH2þROOH!A þ ROH þ H2O). Thanks to
reaction, peroxidases play many critical roles in biological sys-
tems, such as detoxifying reactive oxygen species [33] (e.g.
glutathione peroxidase) and defending against pathogens
[34] (e.g. myeloperoxidase). Peroxidase (especially HRP) has
been widely used in bio-analytical and clinical chemistry, it
employed as a conjugate to an antibody for enzymatically
catalyzing colorimetric substrates for signalling or imaging
[35]. Novel sensing platforms designed for both H2O2 and
glucose detection by Fe3O4 nanoparticles as peroxidase [36].
The results of these initial studies stimulated rapidly expand-
ing interests in the use of iron oxide nanomaterial as a perox-
idase mimic. Among them, Fe3O4 (magnetite) nanomaterial
have studied well. Magneto ferritin (Fe2O3 in ferritin) nano-
particles are employed for targeting and visualizing tumour
tissues [37]. GU et al. showed, iron oxide nanoparticles (both
Fe3O4 and g-Fe2O3) exhibited dual enzyme mimetic proper-
ties including catalase and peroxidase [37].
a. (Fe3þþ H2O2!FeOOH2þþHþ, FeOOH2þ!Fe2þþH2O,
Fe þH2O2!Fe3þþOH þ H) b. (Fe3þþH2O2!FeOOH2þþHþ,
2þ
FeOOH2þ!Fe2þþHO2, HO2!!HþþO2, HO þ HO2/

O2 !H2O þ O2)
Other nanomaterials have been studied for oxidase
mimetic properties. Fe2O3 nanowires explored as a sensor for
glucose detection using their oxidase-like activity [38]. The
non-enzymatic glucose sensor was fabricated with a Fe2O3
nanowire [34]. Also, Iron oxide nanoparticles using magnetic-
ally isolate and purify proteins, DNA, viruses and even whole
mammalian cells [37]. Autophagy or programmed cell death
2 (PCD2) has attracted a great deal of research interest in
tumour biology in recent years. In general, autophagy is elim-
inating the non-functional bio-molecules even organelles
from cellular milieu [35]. Novel iron oxide NPs synthesized
that induce autophagy in the lung cancer cell line (A549) and
not in normal cells (IMR-90) [36]. Notably, autophagy corre-
lated with ROS production as well as mitochondrial damage.
Protection against ROS clearly suggested the implication of
ROS in hyper-activation of autophagy and cell death. Pre-
treatment of cancer cells with 3-MA (an autophagy inhibitor)
also exhibited ROS induction mitochondrial damage and pro-
mote cellular death in cancer cells. These results confirmed
that iron oxide NPs induce classical mTOR pathway in A549
cells. According to the evidence, iron oxide NPs may trigger
cancer cells specifically. One of the most wide nanomaterial
via numerous reports in the literature, testify to their poten-
tial applications in medical diagnostics, controlled drug
release and separation technologies, is superparamagnetic
iron oxide (Fe3O4) nanoparticles [39]. These nanoparticles are
using in sensing, imaging, separation and capture of analytes
[40]. They have used for (bio) analysis, (bio) electrocatalysis,
drug delivery, bacteria inactivation [41] and Lithium-Ion
Batteries [42,43], Stem cell tracking, which is an emergent
field of regenerative medicine, following the stem cells fate
after their introduction in the body [44]. Also, upper-para-
magnetic iron oxide (SPIO) nanoparticles are very useful for

Figure 1. Biomedical and industrial applications of nanomaterials.
mesenchymal stem cells growth [45]. Ferro-carbon-promoted
cell growth thanks to its ability to diminish intracellular H2O2
through intrinsic peroxidase-like activity [46]. Also, ferro-car-
bon may accelerate cell cycle and proliferation, which may be
mediated by the free iron (Fe), released from lysosomal deg-
radation and involves the alteration of Fe on the expression
of the protein regulators of the cell cycle [47]. Also, some of
the medical applications including Transplant monitoring in a
study for therapy of diabetes via transplant pancreas and
monitoring by iron oxide nanoparticles for tissue transplant-
ation [48]. Targeted cell death of tumour cells through con-
trolled heating of the damaged tissue via Engineering the
magnetic nanoparticles for Hyperthermia is based on mag-
netic nanoparticle [49]. Notably, Magnetic nanoparticles have
promising biomedical applications, especially in drug delivery
and tissue engineering [50] (Figure 1). Also, iron oxide can
act as peroxides mimics [51]. There is growing evidence that
magnetite nanoparticles, in fact, possess an intrinsic enzyme
mimetic activity similar to that found in natural peroxidases,
which are widely used to oxidize organic substrates in the
treatment of wastewater or as detection tool [52]. Peroxidase
enzymes activate as hydrogen peroxide to perform numerous
oxidations in nature [53,54]. Also, peroxidases (enzymes that
catalyze oxidation reactions) are popular detection tools
because they simplify colour changes in the presence of cer-
tain dyes. For example, immune-absorbent assay ELIZA tests
[55]. They are also useful in the treatment of waste water for
oxidizing organic substances [56]. However, the wide poten-
tial applications of the peroxidase-like activity of iron oxide
nanoparticles in medicine and biotechnology remain to be
understood yet. A recent study, performed by Gao et al.,
found that the Fe3O4 magnetic nanoparticles (MNPs) were
intrinsically active catalyst for some oxidation reactions, being
similar to natural horseradish peroxidase (HRP) [57]. The per-
oxidase-like nature of Fe3O4 MNPs was employed to replace
the enzyme HRP used in H2O2 detection and immune-absorb-
ent assay and was also explored for the applications in the
degradation of phenolic and aniline compounds [58]. Another
application of Iron oxide as peroxidase including diagnostic
kit for hydrogen peroxide (H2O2) and glucose detection [59].
ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY 1071
Experimental studies demonstrated that the H2O2-activating
ability of Fe3O4 MNPs is not so close to the removal of hydro-
gen superoxide, but it may modify by increasing the
H2O2-activating ability of Fe3O4 MNPs of refractory organic
pollutants from wastewaters [60]. H2O2 detection is useful in
many fields such as biology, medicine, environmental protec-
tion and the food industry [61]. There is a higher efficient
way to Glucose detection via glucose oxidase (GOx) [62].
Fe3O4 MNPs function is on the base of Carboxyl-modified let-
ter oxide (GOCOOH) to possess intrinsic peroxidase-like activ-
ity and catalyze the reaction of peroxidase substrate 3,3,5,5-
tetramethylbenzidine (TMB) in the presence of H2O2 to pro-
duce a blue colour reaction [63]. Highly sensitive and select-
ive colorimetric method for glucose detection has developed
in a buffer solution or diluted blood and fruit juice samples
[64,65]. Glucose detection is a promising method in clinical
and food analysis [66]. Moreover, glucose concentrations in
serum samples could be accurately and selectively detected
over several other sugars, such as galactose, lactose, man-
nose, maltose, arabinose, cellobiose, raffinose and xylose [66].
In the recent years, nanoparticle-based techniques for DNA
detection has developed [67]. The small labelled size, bio-con-
jugation ability and the unusual optical and electrical proper-
ties of metal nanoparticles make them unique tools for DNA
detection [68]. Semiconductor nanoparticles have been exten-
sively used as labels in electrochemical biosensors, especially
DNA sensors. For instance, iron nanoparticle used for labelling
DNA, DNA probe labelled with gold coated iron core-shell
nanoparticles and dissolved the iron-containing nanoparticles
following DNA hybridization, the released iron ions were
determined by cathode stripping voltammetry in the pres-
ence of the 1-nitroso-2-naphthol ligand addition a bromate
catalyst [69]. Double-stranded DNA’s shielding against MNPs’
mimicking activity was combined with PCR, a label-free col-
orimetric platform for DNA sensing developed. Also, aptamers
are selected ssDNA or ssRNA that can specifically bind to a
target and can be considered as nucleic acid versions of an
antibody [70]. Immune-assay is an application via MNPs that
help to detect staphylococcal enterotoxin via magnetic nano-
particles [71]. It has performed due to functionalized antibody
1072 J. GOLCHIN ET AL.
coated on magnetic nanoparticles captured the enterotoxin
antigen from solution [72]. Then, bacterial toxin isolated via
magnetic separation, and amplified the surface plasmon res-
onance (SPR) [73]. In a study by Ibrahim et al., an immuno-
assay was used for the detection of C-reactive protein (CRP)
from rapid whole blood magnetic permeability. The assay
employed monoclonal anti-CRP antibody conjugated to dex-
tran iron oxide nanoparticles (70 nm) as superparamagnetic
labels and polyclonal anti-CRP antibody conjugated to silica
microparticles (to enhance sedimentation of the complex)
[74]. Notably, nanoparticle biosensors with modified antibody
provide three functions including capture, separation and
detection [75]. These novel peroxidase mimic activity of metal
nanoparticles can use for immune-staining. Gu et al. demon-
strated that ultra-small Fe3O4 MNPs were able to replace
expensive enzymes (such as HRP) for immune-histochemistry
staining [76]. In another study, HIV virus was detected by
using antibody biosensing on microfluidic magnetic separator
chip, which they used to concentrate human immunodefi-
ciency virus (HIV) from plasma [77]. Also, super-paramagnetic
nanoparticles conjugated to anti-CD44 to capture the virus,
then passed the particles through a packed bed of 25–75-
lm-diameter iron oxide particles. An external magnet was
used to magnetize the packed bed, which caused the
HIV–magnetic nanoparticle conjugated and trapped, thereby
separating and concentrating them from the plasma matrix.
Off-chip enzyme-linked immune-absorbent assay confirmed
that the HIV virions were concentrated 80-fold over the ori-
ginal solution [78]. Recently, MNPs were used for colorimetric
assay based Fe3O4 magnetic nanoparticle peroxidase mimetic
for the rapid detection of organophosphorus pesticide [79],
acetylcholine esterase (AChE) and choline oxidase (CHO).
H2O2 over-produced in the presence of acetylcholine, then
both the enzymes AChE and CHO were catalyzed. H2O2 then
activates MNPs to catalyze the oxidation of colorimetric
Figure 2. Antioxidant properties of nanoparticles and possible therapeutic applications.
substrates to produce a colour reaction [80]. After incubation
with the organophosphorus neurotoxins, the enzymatic activ-
ity of AChE was inhibited and produced less H2O2, resulting
in a decreased catalytic oxidation of colorimetric substrates
over MNP peroxidase mimetic, the companion by decrease
colour intensity [81].
Cobalt oxide as catalase and peroxidase
Another metal-0base nanoparticle by peroxidase and catalase
enzyme mimic, cobalt oxide, catalyze this reaction as follows:
2O2 þ 2 Hþ ! H2O2þO2 [4]. For example, peroxidase-like
activity was used for wastewater treatment by cobalt-doped
graphitic carbon nitride (Co-g-C3N4) materials [82], as catalase
activity for sensitive and fast sensor of detection H2O2.
Another catalytic application of Co3O4 is the calcium detec-
tion of milk because of increasing significant presence of cal-
cium ion [82]. Also, it can be in peroxidase and oxidase-like
activity that is useful for colorimetric and glucose detection
[83]. The high-redox potential of Co3þ/Co2þ makes this nano-
particle more stronger than others compared to other metal-
based nanomaterial. Thus, the high peroxidase-like activity
designed a new immunohistochemical assay [84]. Avastin
antibody conjugated onto the surface of Co3O4 nanoparticles.
The conjugates obtained were used to detect vascular endo-
thelial growth factor (VEGF) that was overexpressed in
tumour tissue. It may be effective for tumour detection
[52,84]. Co3O4 nanoparticles (NPs) as peroxidase mimics to
catalyze the oxidation of chromophoric substrates by H2O2.
For the detection of H2O2 and glucose, substrates surveyed
even in real samples. Antioxidant capabilities of Co3O4 com-
pared with three natural antioxidants including, gallic acid
(GA), tannic acid (TA) and ascorbic acid (AA) [85] (Figure 2).
Then, enzyme mimics can be used to evaluate antioxidant
capabilities and to screen enzymes inhibitors. In addition,

Co3O4 by oxidase-like activity can used for the detection of
glutathione via TMB-O2-Co3O4 nanotube system [86]. Copper
oxide when used as oxidase mimics CuO nanoparticles show-
ing peroxidase-oxidase mimicking activity. Thus, have same
activity like other metal oxide nanoparticles such as glucose
and L-lactate detection by peroxidase activity [84–86]. Also,
another study shows cupric oxide nanoparticle can be used
as chemiluminescence cholesterol sensor for detection via
peroxidase mimicking [81,85]. Zn–Cuo material is used as a
peroxidase to detect three antioxidants tannic acid, tartaric
acid and ascorbic acid in addition to glucose detection
[58,86], as well as Zn-Cu NPs, when compared to the men-
tioned antibodies have some potential to act like these anti-
bodies [58]. However, Yan Xo et al. showed Cu2þ as an
oxidase mimic is more efficient than Cu/Cuo nanoparticles for
histidine detection even in serum or urea detention in pres-
ence of O-phenylenediamine (OPD) [59].
Manganese dioxide as oxidase
MnO2 nanomaterials with different morphologies (i.e. nano-
sheets, nanospheres, nano-sticks, nano-complexes and nano-
wires) have also been studied to determine their oxidase and
peroxidase and catalase mimicking activity [60]. Liu et al.
showed that BSA-stabilized Mnoþ2 can be used instead of
HRP enzyme and in the detection of goat anti-human in
immunoassay technic as a colorimetric application [60]. In a
study, MnO2 nanosheet was used for detection of
Glutathione via Electrochemical luminescence [61].
Vanadium pentoxide as peroxidase
Vanadium catalysis showed the following reaction: R-
H þ Br þ H2O2!R-Br þ H2O þ OH. Mono-crystalline VO2 (A)
nanoplates were synthesized according to hydrothermal
protocol. VO2 (A) nano-plates showed outstanding peroxid-
ase-like activity and mimics peroxidase activity [63]. Also, van-
adate has halo peroxidases activity in marine macro-algae
due to catalyzing the 2e  oxidation, by H2O2. Vanadium is a
Lewis acid, forming an intermediate peroxide/hydroperoxide
complex. Additionally, the complex can protect the algae
against biofilm formation. Towards the biocidal (anti-bacterial)
potential of the peroxidases [62], another application of van-
adium peroxidase is neutralization of biofilms by mimic van-
adium halo peroxidases [61]. Nanowires had catalytic activity
towards peroxidase substrates (such as ABTS and TMB) in the
presence of H2O2 as demonstrated in a study from Trammel’s
group. Functional materials exerted a strong antibacterial
activity against both Gram-negative and Gram-positive
bacteria.
Gold nanomaterials
Gold nanoparticles (GNPs) mimic oxidase. Glucose has been
detected by GNPs. According to glucose oxidase mechanism
(AredþO2þH2O!AoxþH2O2 and AredþO2!AoxþH2O and
Aredþ O2!AoxþO2), studies suggested a mechanism, which
maybe glucose that firstly adsorb onto the gold
ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY 1073
nanoparticles. Later, one oxygen reacts with the adsorbed
glucose and forms the products which are Gluconic acids and
H2O2. Gold nanoparticles have used to successfully detect tar-
get DNA or microRNA by the hybridization of the nucleic
acids and enzyme activity. Tao et al. use from a synergistic
effect of graphene oxide–gold nanocluster (GO-AuNC) hybrid
for cancer cell detection by constructed as an enzyme mimic
that is able to show high catalytic activity over a broad pH
range, especially at neutral pH [87]. Gold nanoparticles with
either positive or negative surface charges surprisingly
showed peroxidase mimicking activity [88]. Peroxidase-like
activity is used for colorimetric detection of urea, urease and
urease inhibitor [89]. Gold nanoparticles based on peroxidase
function are used to detect kanamycin residue by cataly-
zingthe reaction between H2O2 and reduced thionine to pro-
duce oxidized thionine [67]. A study by Liu et al. showed a
great potential of processing gold nanoparticle via PAMAM
dendrimer as primary neural protection against oxidative
damage via acting like peroxidase [90]. As a common reactive
oxygen species, H2O2 is widely used for bacterial inactivation
and wound disinfection. Water-soluble Au nanocrystal (NC)
micelles with an inserted catalytic Cu (II) centre that act as
excellent nanozyme models for imitating ribonuclease were
constructed by supramolecular self-assembly. The study of
the catalytic behaviour of Au NC micelle catalysis showed
that the Au NC micelles exhibited dramatic ribonuclease-like
activity [91]. Gold nanoparticles use other material to fabri-
cate the Au-Pt nanorods and Au-M (M ¼ Bi, Pd and Pt) nano-
structures to mimic enzyme. Chang et al. demonstrated that
bismuth– gold nanoparticles exhibited peroxidase-like activity
[92]. Wu, Yin et al. extended the previous studies to bimetal
nanoparticles, i.e. Au-Pt nano rods. The Au-Pt nano rods
showed multiple enzyme mimetic capabilities. Au-Ag hetero-
geneous nano rods as nanozyme interfaces with peroxidase-
like activity and their application for one-pot analysis of
glucose at nearly neutral pH [82]. Also, AgM (M ¼ Au, Pd and
Pt) nanostructures have enzyme properties, and a series of
silver-based bimetallic nanostructures, i.e. AgM (M ¼ Au, Pd
and Pt), oxidized colorimetric substrates to correspond prod-
ucts with H2O2, displaying peroxidase-like activity.
Platinum nanomaterial
Platinum nanoparticles encapsulated by apo-ferritin (PtNP-
apo-ferritin) and synthesized to detoxify reactive oxygen spe-
cies. The PtNP-apo-ferritin exhibited SOD-like in vitro [93].
PtNP-apo-ferritin uptake by cells via a ferritin-receptor-medi-
ated process and increased cell viability under stress condi-
tion. Compared to ceria nanoparticles, the SOD-like activity of
PtNP@apo-ferritin is lower on weight basis [94]. Platinum
nanomaterials can mimic catalases and peroxidase [95]. Also,
the PtNP-apo-ferritin exhibited dual enzyme mimic behav-
iours (catalase and peroxidase), both activities dependent on
pH and temperature. Catalase activity enhanced by increasing
pH and temperature while peroxidases activity have a max-
imum value at physiological temperature and slightly acidic
conditions. The catalytic activities were dependent on Pt con-
tent, with higher Pt content having better activities [95].
Recently, Liu et al. revealed that platinum nanoparticles
1074 J. GOLCHIN ET AL.
(Pt NPs) exhibit catechol oxidase-like activity, oxidizing poly-
phenols into the corresponding o-quinones [96].
Carbon-based nanomaterial
Carbon-based nanomaterial, such as fullerene, graphene, car-
bon nanotubes and their derivatives, mimic various natural
enzymes [97]. The peroxidase-like activity of CNTs have
reported in another study [98]. The intrinsic peroxidase-like
activity of single-walled carbon nanotubes (SWNTs) was inves-
tigated by Qu et al. [74]. Similar to HRP, its activity was pH,
temperature and H2O2 dependent. Graphene oxide was also
found to possess intrinsic peroxidase. Mimicking activity
depending on surface-to-volume ratio as well as high affinity
towards organic substrates, graphene oxide showed a higher
affinity towards TMB than HRP (Km, 0.0237mM for graphene
oxide vs. 0.275 mM for HRP), but a lower affinity towards
H2O2 than HRP (Km, 3.99 mM for graphene oxide vs. 0.214 mM
for HRP). CNTS was used to detect H2O2 and glucose. Other
applications include metal ion detection, DNA detection,
aptasensors and immunoassay.
Conclusion
Overall, metal nanoparticles surprisingly mimic some bio-
active compound. When these common domains share
between nanoparticles and enzymes, altered production of
bioactive peptide is possible. The point of this cutting-edge
technology includes direct or indirect manipulation of some
biological pathways, medical diagnostics and environmental
toxicology. For these reasons, metal nanoparticles are a good
candidate to replace some complicated and cost-effective
enzymes or using them as a novel and unique techniques in
the medical laboratory. Recent adventures in this field includ-
ing targeting tumour tissue and molecular imaging expand
the molecular therapy horizon. Also, nanozymes have applica-
tions in microbial detection strategy. For instance, nanozyme
developed to diagnose Ebola. Applications of nanozymes
including bioanalytical and electrochemical techniques are
growing besides medical uses.
Disclosure statement
The authors report no conflicts of interest. The authors alone are respon-
sible for the content and writing of this article.
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