Catalytically Active Nanomaterials Lin, 2014
Catalytically Active Nanomaterials Lin, 2014
pubs.acs.org/accounts
1. INTRODUCTION biology has also ignited intensive research efforts for designing
Enzymes are extremely efficient at catalyzing a variety of functional nanomaterials that exhibit various properties intrinsic
reactions with high substrate specificity, activities, and yields to enzymes.6,8−25 A variety of nanoscale materials, such as
under mild reaction conditions.1,2 As a result, there is significant cerium oxide nanoparticles,8−10 magnetic nanoparticles,3,11,12
interest in utilizing enzymes for applications in biosensor, gold nanoparticles (AuNPs),13−18 V2O5,19,20 PtPd−Fe3O4,21,22
pharmaceutical processes, food industry, and agrochemical graphene oxide, 23 and carbon nanotubes,24 have been
production. However, problems, including their low operational discovered to possess unique enzyme-mimic catalytic activities.
stability (denaturation and digestion), sensitivity of catalytic Due to the outstanding catalytic property of thiol monolayer
activity to environmental conditions, difficulties in recovery and protected nanogold, Scrimin, Pasquato, and co-workers called it
recycling, and high costs in preparation and purification, greatly “nanozyme” in analogy to the nomenclature of catalytic
limit their applications.3,4 To circumvent aforementioned polymer (synzyme).25 Here, to highlight enzyme-like activity
limitations, artificial enzymes have been established as low- of the nanomaterial, we adopt the term ‘‘nanozyme’’ to describe
cost and highly stable alternatives to natural enzymes.5−7 So far,
design of artificial enzymes has very rapidly emerged as a lively Received: October 16, 2013
field of research. Recently, the merging of nanotechnology with
© XXXX American Chemical Society A dx.doi.org/10.1021/ar400250z | Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research Article
Figure 3. Schematic illustration of procedures for targets detection by using the catalytic GH and targets-induced assembly.29 Copyright 2013,
Elsevier.
but in recent years AuNPs with different surface modifications concentration of a buffer solution.42 Therefore, we offered an
have been found to exhibit GOx- or peroxidase-like effective way to eliminate the incompatibility of different
activity.14−16,46 After that, Fan et al. have constructed a new reactions and piece different activities together into a self-
sensor platform for sensitive detection of DNA and microRNA organized artificial cascade reaction. Initially, EMSN-AuNPs
by utilizing this GOx-like activity.17 However, the potential of catalytically oxidized glucose by oxygen to yield gluconic acid
AuNPs as enzyme mimics is limited by their relatively low and hydrogen peroxide in 0.5 mM phosphate buffer, pH 7.4.42
catalytic activities and stability.17 In addition, single-component Next, gluconic acid produced in the system decreased the
AuNPs cannot simultaneously possess dual enzyme-like ambient pH, which could activate the peroxidase-like activity of
functionalities, as unsupported AuNPs with different surface EMSN-AuNPs.42 In the presence of TMB, EMSN-AuNPs
properties only keep one enzyme-like functionality active while could produce a blue color reaction owing to the oxidation of
the other catalytic activity can be completely blocked.15,46 TMB by cumulative product H2O2 (Figure 5D).42 This is the
Recently, the emergence and recent advance of nano- first example using nanomaterials alone as dual artificial
technology opens new opportunities for the development of enzymes for mimetic cascade catalysis.42 Therefore, the proof-
nanoparticles with stable and high catalytic activity.47,48 With of-principle results take an important step forward in
this in mind, we set out to investigate the fabrication of AuNPs developing enzyme mimics for realizing more complex
encapsulated in expanded mesoporous silica support (EMSN) functions.
(Figure 5A).42 EMSN as the skeleton assists the synthesis of a Recently, noble-metal nanoclusters have also become a
burgeoning area of scientific interest.49 Intriguingly, Wang et al.
discovered that bovine serum albumin-stabilized gold clusters
(BSA-AuNCs) possess intrinsic peroxidase-like activity.50
Inspired by these initial results, our group developed an easy
prepared fluorometric and colorimetric dual channel probe for
dopamine by using BSA-AuNCs.43 The as-prepared BSA-
AuNCs exhibited strong fluorescence and high peroxidase-like
activity.43 In the presence of dopamine, the fluorescence
intensity of the AuNCs decreased significantly through a
photoinduced electron transfer process (Figure 6A).43 Mean-
mimics.3,8−12,19,20 Among them, cerium oxide nanoparticles8−10 7B).51 To create this nanogated ensemble, ferrocene groups
and magnetic nanoparticles3,11,12 are two most widely used were first introduced onto the outlet of mesoporous silica.51
metal oxide catalysts. But this introduction will focus on our Therefore, β-CD-functionalized CeO2 nanoparticles could cap
interests in making use of CeO2 nanoparticle based ones.51 onto ferrocene-modified mesoporous silica through host−guest
CeO2 nanoparticles, which exist in a mixed valence state interactions.51 After internalization into A549 cells by a
(Ce3+, Ce4+), possess many unique properties that have proven lysosomal pathway, the ferrocenyl moieties were oxidized to
to be of high utility in biomedical and catalytic applica- ferrocenium ions by CeO2 lids, which could trigger uncapping
tions.8,52−57 Recently, they have been reported to possess of the CeO2 and cause drugs release.51 Moreover, as cancer
multienzyme, such as SOD,10,54 catalase,9 oxidase,8,56 and cells have a more acidic cytosolic pH than normal ones, CeO2
phosphatase,57 mimetic properties. For instance, Perez’s group with oxidase-like activity could oxidize some intracellular and
reported that nanoceria has an intrinsic oxidase-like activity at extracellular components to induce cancer cell apoptosis
acidic pH values, as it can quickly oxidize a series of (Figure 7C).51 This proof of concept provides a novel route
colorimertic dyes without any oxidizing agent.8 Following for using switchable enzymatic activity of CeO2 as capping
these early works, we found that the pH-tunable oxidation agents in the field of versatile controlled delivery nanodevices.
ability of nanoceria to ferrocenecarboxylic acid (Fc-COOH).51
After incubation nano-CeO2 with Fc-COOH solution at pH 3. EXPLORING EFFICIENT MODULATORS
7.4, there was no significant change in absorption or color.51 To keep up with the overall performance of natural enzymes,
While after incubation at pH 4.5, the mixture solution displayed one major activity is searching more efficient nanozymes, as
a yellow to green color change with a new absorption band reflected by numerous recent publications.8−25 An alternative
appeared at 632 nm, which suggested the ferrocenyl moieties strategy is exploring modulators to further enhance the
could be oxidized to positively charged ferrocenium ions by performance of existing artificial enzymes. Below, we introduce
nano-CeO2 under acidic pH (Figure 7A).51 More interestingly, three exciting push in the use of efficient modulators on
artificial catalytic systems.58−60
3.1. Ionic Liquid
In spite of the fascinating features of present peroxidase mimics,
one of the main shortcomings that these enzyme mimics
(including EMSN-AuNPs) suffer is that their catalytic perform-
ance at high temperature is far below expectations.3,23,58 As
they usually exhibit superior thermal stability to natural
enzyme,3,23,58 we rule out the possibility of this phenomenon
caused by nanozymes themselves, and point out that the
thermally induced instability of enzymatic product ABTS•+
inhibit their catalytic activity at high temperature (Figure 8A).58
Inspired by the unique properties of the ionic liquid, we
reasoned that it could serve as a stabilizing agent for improving
thermal stability of ABTS•+, and subsequently enabling high-
temperature reaction that were not working efficiently in buffer
solution. Indeed, in the presence of ionic liquid, their catalytic
activity and product stability at high temperature were much
Figure 9. (A) Schematic illustration of the high catalytic activity of synergistic GO-AuNCs hybrid in a fairly broad range of operating pH.59 (B)
Time-dependent absorbance changes at 652 nm in the presence of (1) GO, (2) AuNCs, and (3) the GO-AuNCs hybrid at pH 7.0.59 (C) Schematic
representation of preparation of GFA and cancer cell detection by using target-directed GFA.59 Copyright 2013, Wiley-VCH.
Figure 10. (A) Increased catalysis of nucleoside triphosphates (NTPs) to oxidase-like activity of nanoceria.60 (B) Schematic illustration of the
coupling of the oxidative reaction with the NTP hydrolysis reaction.60 Copyright 2013, Wiley-VCH.
greater than that obtained in the absence of ionic liquid (Figure catalytic activity at neutral pH, whereas, both GO and AuNCs
8B, C).58 Such a positive effect is possibly connected with their showed almost no activity.59 Significant activity enhancement
weak interactions with product, a large number of cations and indicated that GO played an important role in modulating the
anions, and their greater solvation power.58 Our findings pave catalytic activity of the AuNCs. Initially, TMB could be
the way to applying ionic liquid as a positive modulator in absorbed onto GO efficiently as GO possessed high surface-to-
nanozyme-based catalytic reactions. volume ratios as well as high affinity for hydrophobic
3.2. Graphene Oxide molecules.23 After that, the active site of AuNCs and substrate
TMB were confined in the same nanoscale region, which could
Compared with other nanomaterial-based peroxidase mimics, greatly enhance the catalytic activity of AuNCs.59 This
AuNCs as nanozymes are more prominent for bioanalysis due mechanism was similar to that of natural enzymes in which
to their small size, excellent stability, and biocompatibility.50 the extraordinarily high catalytic efficiency was largely due to
Despite these favorable properties, AuNCs usually suffer one the ability to bring substrates into proximity with their active
main shortcoming: its optimum reaction occurs in acidic sites.2 Consequently, the hybrid catalyst showed an excellent
solution, which seriously restrict its applications in biological peroxidase-like activity over a broad pH range, thus opening
systems where a near neutral pH is required. To overcome this this novel catalytic system for a multitude of potential
drawback, we demonstrated that GO could serve as the enzyme applications in biological systems.59 For instance, upon
modulator to regulate the peroxidase-like activity of lysozyme- conjugation of folic acid to the hybrid, we have utilized the
stabilized AuNCs (Figure 9A).59 The most exciting feature of target-functionalized nanohybrid (GFA) as a robust nanoprobe
the synergistic GO-AuNCs hybrid is that it exhibits high for selective, quantitative, and fast colorimetric detection of
catalytic activity over a broad pH range, even at neutral pH.59 cancer cells at physical pH, which would provide a drastic
As shown in Figure 9B, hybrid catalyst exhibited excellent positive effect on diagnosis and prognosis (Figure 9C).59
F dx.doi.org/10.1021/ar400250z | Acc. Chem. Res. XXXX, XXX, XXX−XXX
Accounts of Chemical Research Article
3.3. Nucleoside Triphosphates bringing substrates into proximity with active sites.2 (3) The
Very recently, we reported that nucleoside triphosphates types of nanozyme catalytic reactions are limited to only redox
(NTPs) could be used as coenzymes improve the oxidase-like type reactions and hydrolytic reactions, whereas enzymes are
activity of nanoceria and that activity enhancement is related known to catalyze various types of biochemical reactions.
with the type of NTPs (Figure 10A).60 Since the nanoceria has Therefore, further investigations are indeed essential to
both oxidase-like8 and phosphatase-like57 activities, such construct novel nanozymes for catalyzing other types of
increased catalysis resulted from the coupling of the oxidative reactions. (4) Rational design of efficient nanozymes is still
reaction with the NTP hydrolysis reactions (Figure 10B).60 In remains a big challenge. A solution to this problem may be
addition, the difference of the improvement effect reflected the offered by the rapidly growing field of nanotechnology.47,48
different dephosphorylation catalytic activities of nanoceria to Besides resolving those problems mentioned above, future
the NTP used.2 Based on these intriguing results, we also work in nanozymes technology is likely to continue to focus on
developed series effective and high-throughput colorimetric the exploitation of their potential applications and piece these
assays for single-nucleotide polymorphism (SNP) typing.60 synthetic nanocomponents together into organized functional
systems.
4. CHALLENGES AND FUTURE OPPORTUNITIES
5. CONCLUSIONS
To better understand the challenges and opportunities of
nanozymes, the main advantages and disadvantages of nano- Over the past few decades, natural enzymes have been a
zymes and natural enzymes are presented in Table 1. Under constant source of inspiration for chemists in their efforts to
comparison, artificial enzymes are less vulnerable to denatura- create synthetic structures that mimic their functions and
tion, low-cost, easy to obtain, and more stable to promote catalysis. In this Account, we summarized our recent
biodegradation. In addition to the above advantages shared development in the field of nanozymes. The studies featured
with other enzyme mimics, nanozymes also possess their herein attempt to understand and apply nanomaterials as
unique features, including large surface area for further enzyme mimics and, more significantly, shed light on the
modification and other specific functions besides catalysis improvements of these catalytic nanomaterials and their
(e.g., magnetic property of magnetic nanoparticles). promising applications in biomedical diagnosis, environmental
Despite these advantages, there are four important challenges monitoring, and therapeutics.
that remain for efficiently directing the development of Despite the fact that there are still many unresolved issues
nanomaterial-based artificial enzymes (Table 1). (1) Nano- and challenges, the unique properties and functions of these
zymes usually exhibit the relatively low catalytic activity, in enzyme mimics and the promising results exhibit that this field
comparison with natural enzymes. In this respect, the will continue to thrive and mature in the years to come.
development of enzyme mimics to be able to show excellent
enzyme-like activity will have great potential for the next
generation of mimetic enzyme systems. Alternatively, our
■ AUTHOR INFORMATION
Corresponding Author
recent works have started to address this issue by exploring *E-mail: [email protected].
efficient modulators.58−60 (2) Nanozymes often have a lower
binding affinity and lower specificity for substrate than natural Notes
enzymes. In contrast, due to their unique catalytic micro- The authors declare no competing financial interest.
environments, enzymes exhibit high binding affinity and
Biographies
substrate specificity. In their active site, a pocket is available
for substrate recognition and catalysis. For this reason, the Youhui Lin received his B.S. (2008) from Fuzhou University, China.
exterior surfaces of nanomaterials may be coated with He then joined to the Changchun Institute of Applied Chemistry as a
functional groups similar to those exposed by enzymes,6 thus Ph.D. candidate, majoring in Chemical Biology. His current scientific
enhancing their binding affinity and substrate specificity. interest is focused on the fabrication of nanozymes using smart
Meanwhile, it can accelerate the chemical transformations by materials.
Jinsong Ren received her B.Sc. degree at Nanjing University in 1990, (13) Pengo, P.; Polizzi, S.; Pasquato, L.; Scrimin, P. Carboxylate−
and Ph.D. from Changchun Institute of Applied Chemistry, Chinese Imidazole Cooperativity in Dipeptide-Functionalized Gold Nano-
Academy of Sciences in 1995. From 1996 to 2002, she worked in particles with Esterase-like Activity. J. Am. Chem. Soc. 2005, 127,
School of Medicine, UMMC and Department of Chemistry and 1616−1617.
(14) Comotti, M.; Della Pina, C.; Matarrese, R.; Rossi, M. The
Chemical Engineering, California Institute of Technology. In 2002, she
Catalytic Activity of “Naked” Gold Particles. Angew. Chem., Int. Ed.
took a position as a principal investigator at Changchun Institute of
2004, 43, 5812−5815.
Applied Chemistry, Chinese Academy of Sciences. Her current (15) Luo, W.; Zhu, C.; Su, S.; Li, D.; He, Y.; Huang, Q.; Fan, C. Self-
research is mainly focused on drug screening and DNA-based Catalyzed, Self-Limiting Growth of Glucose Oxidase-Mimicking Gold
nanofunctional materials. Nanoparticles. ACS Nano 2010, 4, 7451−7458.
Xiaogang Qu received his Ph.D. from the Chinese Academy of (16) Comotti, M.; Della Pina, C.; Falletta, E.; Rossi, M. Aerobic
Sciences (CAS) in 1995 with CAS President’s Award. He moved to Oxidation of Glucose with Gold Catalyst: Hydrogen Peroxide as
Intermediate and Reagent. Adv. Synth. Catal. 2006, 348 (3), 313−316.
the United States afterward and worked with Professor J. B. Chaires at
(17) Zheng, X.; Liu, Q.; Jing, C.; Li, Y.; Li, D.; Luo, W.; Wen, Y.; He,
the Mississippi Medical Center and Nobel Laureate Professor Ahmed. Y.; Huang, Q.; Long, Y.-T.; Fan, C. Catalytic Gold Nanoparticles for
H. Zewail at the California Institute of Technology. Since late 2002, he Nanoplasmonic Detection of DNA Hybridization. Angew. Chem., Int.
is a professor at Changchun Institute of Applied Chemistry, CAS. Ed. 2011, 50, 11994−11998.
From 12/2006 to 05/2007, he visited the group of Nobel Laureate (18) Bonomi, R.; Selvestrel, F.; Lombardo, V.; Sissi, C.; Polizzi, S.;
Professor Alan J. Heeger at UCSB. His current research is focused on Mancin, F.; Tonellato, U.; Scrimin, P. Phosphate Diester and DNA
ligand-nucleic acids or related protein interactions, and biofunctional Hydrolysis by a Multivalent, Nanoparticle-Based Catalyst. J. Am. Chem.
materials for advanced medical technology. Soc. 2008, 130, 15744−15745.
■
(19) André, R.; Natálio, F.; Humanes, M.; Leppin, J.; Heinze, K.;
Wever, R.; Schröder, H. C.; Müller, W. E. G.; Tremel, W. V2O5
ACKNOWLEDGMENTS Nanowires with an Intrinsic Peroxidase-Like Activity. Adv. Funct.
We acknowledge financial support from National Basic Mater. 2011, 21, 501−509.
Research Program of China (Grant 2012CB720602, (20) Natalio, F.; Andre, R.; Hartog, A. F.; Stoll, B.; Jochum, K. P.;
2011CB936004) and the National Natural Science Foundation Wever, R.; Tremel, W. Vanadium pentoxide nanoparticles mimic
vanadium haloperoxidases and thwart biofilm formation. Nat.
of China (Grants 91213302, 21210002).
■
Nanotechnol, 2012, 7, 530−535.
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