Remote activation of nanoparticulate biomimetic activity by light triggered pH-jump

Article abstract of DOI:10.1039/c8cc04279a

Herein, we report a facile, efficient and versatile method for the photo-regulation of pH-dependent activities of artificial enzymes by incorporating flash photolysis reagents. Under light excitation, a persistent pH shift is achieved by proton release fr

Full text of DOI:10.1039/c8cc04279a

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
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Remote Activation of Nanoparticulate Biomimetic Activity by
Light Triggered pH-Jump
Xiaopei Wang,a Ao Gong,a Wenhao Luo,a Haiqing Wang,a Changxu Lin,a Xiang Yang Liub, a and
Youhui Lina*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Over the past few decades, the capacity of flash
photolysis reagents to induce an enduring change in pH during
light exposure has been widely used for spatial and temporal
Herein, we report a facile, efficient and versatile method for
photo-regulation of pH-dependent activities of artificial enzymes
by incorporating flash photolysis reagents. Under light excitation,
control of acid-catalyzed and pH-sensitive processes.3c, 3d, 4
A
a
persistent pH shift is achieved by proton release from
majority of these reagents possess a 2-nitrobenzyl group,
which serves as an essential role in the photo-labile precursor.
For instance, a commercial molecule 2-nitrobenzaldehyde (2-
NBA) exhibits inherently pKa shift ability by photo-irradiation.
Under the excitation of ultraviolet light, its permanent weak
acidic-form, nitrosobenzoic acid (2-NBS), and proton can be
produced quickly by the intramolecular proton-transfer
reaction.4a The reaction mechanism about such photo-
conversion as well as the kinetics have also been thoroughly
photosensitive 2-nitrobenzaldehyde. Following such change,
controlled activation of oxidase-like activity of nanoceria is
successfully demonstrated.
Recently, due to the merging of nanotechnology with biology,
design and development of functional nanomaterials with
intrinsic enzyme mimetic activities has attracted enormous
research interest.1 As promising candidates of natural
enzymes, these nanomaterial-based artificial enzymes, termed studied.5 Inspired by this light-triggered pH shift and the
phenomenon that many enzyme-mimicking activities of
nanozymes are highly dependent on pH, we develop a simple
and very efficient approach for photo-mediated control of
oxidase-like activity of nanoceria by incorporating
photosensitive 2-NBA. This strategy is not only restricted to
nanoceria-based artificial enzymes and can also be readily
applied to all other kinds of nanozymes.
as ‘‘nanozymes’’, have already been extensively utilized in a
wide variety of applications, including biosensor,
environmental chemistry, and therapeutics.1 Among these,
cerium oxide nanoparticle (CeO2 NP or nanoceria) is one of the
typical nanozymes, which has been discovered to possess
2
multiple enzyme-like activities.1f, For example, nanoceria
exhibits a specific pH-dependent oxidase-like activity,2a which
can rapidly oxidize a variety of organic substrates without any
oxidant, such as hydrogen peroxide. This activity likely comes
from the reversible conversion of the oxidation state between
Ce4+ and Ce3+.2a On the other hand, control and especially
controlled activation of biochemical events can offer many
new opportunities for biotechnology and chemical industry.3
Previous researchers have focused on the manipulation of
enzyme function.3 However, regulation of the activities of
nanozymes has rarely been investigated.3 Therefore, it would
be highly desirable to develop new approaches for controlling
these nanoparticulate biomimetic activities.
Scheme 1. The working principle of controllable oxidase-like activity of dextran-
decorated nanoceria based on photo-induced proton release from pH-jump 2-
NBA.
The working principle of controllable oxidase-like activity
of dextran-decorated cerium oxide nanoparticles by photo-
induced pH-jump 2-NBA is illustrated in Scheme 1. Firstly,
dextran-decorated cerium oxide nanoparticles were
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synthesized based on
a
previously reported procedure.6 with main absorbance peaks at 417 nm (Fig. S3). Very interestingly,
Dextran can serve as an excellent stabilizer based on strong no apparent oxidation of TMB was observed under physiological
coordination interactions between hydroxyl groups of dextran condition, which could be confirmed by the absorbance change of
and rare earth ions.7 The as-prepared cerium oxide TMB (Fig. 1E). Furthermore, pH-dependent studies showed that the
nanoparticles were characterized by transmission electron ability of cerium oxide nanoparticles to oxidize TMB decreased as
microscopy (TEM). The HRTEM image indicated the presence the pH value of the solution increased from 4.0 to 8.0 (Fig. 1F). The
of discrete nanocrystals with an average size of 4 nm as well as above results indicated that the as-prepared nanoceria as an
good monodispersity (Fig. 1A). Our obtained cerium oxide oxidation catalyst behaved in a pH-dependent manner with strong
10
nanoparticles with small sizes are expected to exhibit catalytic activity under acidic environment.2a, We expect such
intriguing catalytic performance.8 Moreover, the preferred characteristic pH-dependent oxidase-like activity could be
plane (111) (d = 0.314 nm) on the surface was observed (Fig. controlled by light if the combination of photosensitive pH-Jump
1B).9 Also, the formation of a face-centered-cubic nanoceria reagents.
core was identified by selected-area electron diffraction
(SAED) and X-ray powder diffraction (XRD) pattern (Fig. 1C and
1D).9
Fig. 2 (A) Absorption spectra of 2-NBA solution prior and after UV excitation (10
min). (B) pH changes of different samples determined by pH meter prior and
after UV excitation (10 min). (C) Absorption spectra and (D) the relative catalytic
activities of TMB reaction solutions under different conditions.
0 unless
otherwise stated. [Nanoceria] = 0.1 mg/mL, [TMB] = 1 mM, [2-NBA] = 4 mM,
[Phosphate buffer] = 0.5 mM.
Before investigating whether light could switch the
oxidase-like activity of nanoceria in the presence of 2-NBA, the
UV responsive properties of 2-NBA and 2-NBA/CeO2 hybrid
solutions was taken into consideration. Upon optical excitation
toward 2-NBA, its acidic-form 2-NBS was promptly generated
as a result of the intramolecular proton-transfer reaction,3c, 5
accompanied with the absorption change of 2-NBA (Fig. 2a and
Fig. S4). During the formation of the nitronate anion, proton
was released simultaneously, which could dramatically
decrease the pH in aqueous solution. To detect the changes in
the solution pH, the acid-base indicator methyl red, which
presents red in pH below 4.4 and yellow in pH over 6.2, was
selected (Fig. S5). Before UV exposure, the indicator displayed
a yellow color in the phosphate buffer solution (0.5 mM, initial
pH 7.0) containing 4 mM 2-NBA. While after excitation of
ultraviolet light, a distinct yellow to red color change was
observed, indicating the pH of the aqueous phase was
decreased (Fig. S5). The solution pH value measured by pH
meter further confirmed that the pH was changed from 7.0
down to 3.6 (Fig. 2B). Without 2-NBA, the excitation of UV light
toward solution could not cause any pH change (Fig. S6). These
experiments indicated that light-triggered proton release from
2-NBA induced the change in pH. Since the dextran-coated
nanoceria has a large number of hydroxyl groups on the
surface, these groups can serve as proton scavengers and
Fig. 1 (A, B) TEM images of as-prepared nanoceria. (C) The corresponding SAED
pattern. (D) Wide-angle powder XRD pattern of nanoceria. (E) The absorbance
changes of different samples as a result of the formation of oxTMB. (F) The pH-
dependent catalytic activity of nanoceria.
To evaluate the oxidase-like activity of cerium oxide
nanoparticles, 3,3’,5,5’-tetramethylbenzidine (TMB) is selected for
an oxidase substrate, which can yield a product (oxTMB) upon
oxidation. In the absence of hydrogen peroxide, cerium oxide
nanoparticles could catalyze the rapid oxidation of substrate TMB
to oxTMB and produced a blue color at pH 4.0 with central
absorbance peaks at 370 nm and 652 nm (Fig. 1E and Fig. S1).
Meanwhile, with the increasing concentrations of nanoceria, the
more oxTMB product was generated (Fig. S2). We selected the
absorbance changes at 652 nm for monitoring the catalytic reaction
to avoid possible interferences from 2-NBA and 2-NBS. To further
confirm
this
oxidase-like
activity,
2,2’-Azino-bis-(3-
ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), is
also utilized as an oxidase substrate. Similarly, nanoceria could also
catalyze the oxidation of ABTS to generate a green color product
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weaken the final pH-jump.4g For this reason; we also texted the Overall, we have demonstrated the feasibility of the above
pH change ability of 2-NBA in the presence of the suitable scheme that we proposed.
concentrations of nanoceria. Importantly, in the system
containing 0.1 mg/mL nanoceria, the presence of 4 mM 2-NBA containing 2-NBA and cerium oxide nanoparticles was highly
after UV irradiation could still cause pH jump of depended on the activated time of ultraviolet light. With the
approximately three units from 7.0 to 4.0 (Fig. 2B and Fig. S6). increasing of excitation time, the pH value decreased from 7.0
Although the pH change ability of 2-NBA/CeO2 hybrid system down to around gradually (Fig. 3). Meanwhile, the
More importantly, the pH change of the system
a
4
was slightly weaker than that containing 2-NBA alone, such corresponding catalytic activity of such system (using TMB as a
resulting pH shift was massive enough to change the oxidase- substrate) could be tuned easily by adjusting the illuminating
like activity of nanoceria remarkably.2a
time (Fig. 3 and Fig. S11). Similar result was also observed for
ABTS-based substrate (Fig. S12). Above results sufficiently
proved the activation efficiency of nanozymes are highly
tunable.
In summary, this study provides a first example of using
flash photolysis reagents for controlled activation of pH-
dependent activity of nanoceria. This strategy presented
herein is simple in design, label-free, non-invasive, and suitable
for almost all different nanozymes. Moreover, the activation
efficiency can be easily tailored. Since control of nanozymes’
activity can modulate their selectivity and catalytic efficiency
and avoid some potential problems,11 our work may open a
range of potential applications in future biomedical, industrial,
and environmental fields.
This work was supported by National Nature Science
Foundation (Nos. 21771150, 21401154, U1405226), 111
project (B16029), the Fundamental Research Funds for the
Central Universities of China (Nos. 20720170011,
20720140528), and Doctoral Fund of the Ministry of Education
(20130121110018).
Fig. 3 The pH change of 2-NBA/CeO2 hybrid system under different illuminating
time and the corresponding catalytical activity under different illuminating time.
[Intial pH] = 7.0, [Nanoceria] = 0.1 mg/mL, [TMB] = 1 mM, [2-NBA] = 4 mM,
[Phosphate buffer] = 0.5 mM.
Conflicts of interest
Next, we addressed the possibility of applying UV light to
switch the oxidase-like activity of cerium oxide nanoparticles in
the presence of flash photolysis reagents. Without the
excitation of ultraviolet light, no distinct activity was observed
for all samples in 0.5 mM phosphate buffer (pH 7.0), even the
presence of both 2-NBA and nanoceria (Fig. 2C and Fig. 2D).
However, the reaction system containing 2-NBA and CeO2 NPs
after UV exposure showed strong ability toward the catalytic
oxidation of TMB to product oxTMB (Fig. 2C). We noted that to
avoid the oxidation of TMB by UV, TMB was added in the
above system after UV exposure. Moreover, the catalytic
ability of activated cerium oxide nanoparticles reached
approximately 97.1% of that at pH 4.0 (Fig. 2D). Above
experiments indicated that the resulting low pH from
photosensitive 2-NBA could almost entirely activate the
oxidase-like activity of nanoceria, and there was no significant
impact on the oxidase-like activity of nanoceria by 2-NBA, 2-
NBS and photoexcitation. In contrast, under the same
condition, neither nanoceria nor 2-NBA alone could catalyze
the oxidation TMB efficiently (Fig. 2C). It meant that without 2-
NBA, only ligh could not activate the activity of cerium oxide
nanoparticles. Also there was no significant impact on the
oxidation state of nanoceria upon the photoexcitation (Fig.
S7). Furthermore, our photo-activation method toward ABTS-
based substrate, citrate-based buffer and pH-dependent V2O5
peroxidase mimic, has also been demonstrated (Fig. S8-S10).
There are no conflicts to declare.
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By incorporating flash photolysis reagents, a facile and
versatile method for photo-regulation of pH-dependent
activities of artificial enzymes is presented.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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ChemComm
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TOC
By incorporating flash photolysis reagents, a facile and
versatile method for photo-regulation of pH-dependent
activities of artificial enzymes is presented.