Light-triggered charge reversal of organic-silica hybrid nanoparticles

Article abstract of DOI:10.1021/ja303118w

A functional nanoparticle with light-triggered charge reversal based on a protected amine-bridged polysilsesquioxane was designed. An emulsion- and amine-free sol-gel synthesis was developed to prepare uniform nanospheres. Photolysis of suspensions of these nanoparticles results in a reversal of the χ potential. This behavior has been used to trigger nanoparticle self-assembly, nanocomposite hydrogel formation, and nanoparticle release, showing the potential of this material in nanoscale manipulation and nanoparticle therapy.

Full text of DOI:10.1021/ja303118w

Communication
pubs.acs.org/JACS
Light-Triggered Charge Reversal of Organic−Silica Hybrid
Nanoparticles
Li-Chih Hu, Yusuke Yonamine, Shih-Hui Lee, Wytze E. van der Veer, and Kenneth J. Shea*
Department of Chemistry, University of California, Irvine, California 92697, United States
S
* Supporting Information
release of therapeutic NPs that function by “direct interaction”
(such as those that capture toxins23 or disrupt deleterious
ABSTRACT: A functional nanoparticle with light-trig-
cells24) still remains a challenge. In this study, we report a novel
gered charge reversal based on a protected amine-bridged
polysilsesquioxane was designed. An emulsion- and amine-
free sol−gel synthesis was developed to prepare uniform
nanospheres. Photolysis of suspensions of these nano-
particles results in a reversal of the ζ potential. This
behavior has been used to trigger nanoparticle self-
assembly, nanocomposite hydrogel formation, and nano-
particle release, showing the potential of this material in
nanoscale manipulation and nanoparticle therapy.
type of BPS NP with charge-reversal functionality triggered by a
photochemical reaction and model studies suggesting its
applications in fields such as nanomaterial self-assembly and
nanoparticle therapy. The design of our nanomaterials features
a negative colloidal charge that is intrinsic to the as-synthesized
BPS NPs. Upon UV irradiation, secondary amine groups
emerge in the bridging moieties, reversing the overall colloidal
charge from negative to positive. BPS NPs with o-nitrobenzyl
carbamate-protected amine25 bridging groups were chosen as
the photoresponsive material to demonstrate this concept.
To prepare the precursor for the nanomaterials, o-nitrobenzyl
chloroformate26 was slowly added to a solution of equimolar
bis(trimethoxysilylpropyl)amine and excess Et3N at −12 °C.
NMR analysis of the reaction mixture showed full consumption
of the chloroformate with ∼3 mol % decomposed chlor-
oformate and ∼3 mol % unreacted monomer. A corresponding
amount of the chloroformate was added. This procedure
yielded o-nitrobenzyl-N,N-bis(trimethoxysilylpropyl) carbamate
(1), the monomer for the photoresponsive BPS materials (eq
1).
here has been substantial progress in the synthesis and
T
applications of uniform, spherical bridged polysilsesquiox-
ane (BPS) xerogel nanoparticles (NPs). Emulsion,1 modified
Stober,2 templated modified Stober,3 and self-assembly4,5
̈
̈
methods were developed for NP synthesis from monomers
spanning a range of water solubilities, shapes, and rigidity.
Applications of BPS NPs include their use as photodeformable
and photopatternable materials,4 cellular-imaging NPs,6 and the
active component in solid-state electrochromic devices.7
Both inorganic and organic moieties can contribute
significantly to the colloidal charge of BPS NPs. While
uncondensed silanol groups (pKa ≈ 4) generally provide
abundant negative charge at pH 5 or higher, recent findings2
have shown that functional organic bridging groups (e.g.,
alkylamines) may contribute positive charge that only partially
compensates for the surface negative charge (negative ζ
potential) under basic conditions but eventually dominates
the surface charge (positive ζ potential) under neutral or acidic
conditions. This phenomenon offers the potential to modulate
the colloidal charge over a wide range.
The self-assembly of NPs based on charge interactions has
been proven to be one of the most effective and reliable
strategies for the fabrication of novel nanostructured materials.
The methods range from layer-by-layer assembly8 for planar or
colloidal structures9 to NP “complexes”,10 superlattices or
crystals,11 and nanocomposites.12 Applications include elec-
tronic devices,13 HPLC stationary phases,14 solar cells,15
imaging quantum dots,16 self-healing hydrogels,17 and ther-
apeutic NPs.18
Typical sol−gel syntheses of SiO2 or organic-silica hybrid
NPs involve reaction in aqueous ammonia solution. Since the
carbamate group is known to be unstable in the presence of
NH3, a protocol for base-catalyzed BPS NP synthesis without
highly nucleophilic reagents was needed. The synthesis of
uniform, spherical BPS NPs (1P) from monomer 1 was
achieved in aqueous solution containing catalysts such as
Na2CO3, NaOH, and KF and 1-PrOH as a a cosolvent (eq 2
and Table 1). Model studies using o-nitrobenzyl-N,N-diethyl
carbamate in the catalyst solutions showed no reaction of the
starting material, suggesting that the carbamate bridging moiety
would be stable under these polymerization conditions.
NPs with charge-reversal capability have recently attracted
attention in the release of therapeutic agents triggered by pH
change19,20 or UV irradiation.21,22 The strength of the latter
strategy lies in its site and time specificity. However, most
current research in the field is focused on triggered release of
therapeutic small molecules or nucleic acids from NPs. The
Received: March 31, 2012
Published: June 25, 2012
© 2012 American Chemical Society
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NPs would be transformed into species with a positive ζ
potential, providing the potential for self-assembly of a shell of
SiO2 NPs on the surface of the BPS NPs (Scheme 2).
Table 1. Amine-Free Modified Stober Synthesis and Size
Control of BPS NPs 1P (A Recipe for Finer Size Control Is
Included in the Supporting Information)
̈
[Na2CO3]
(mM)
[NaOH]
(mM)
[KF]
(mM)
1-PrOH
(%)
[1]
T
D
n a
Scheme 2. Light-Triggered “NP Shell” Assembly
(mM) (°C) (nm)
20
10
10
25
0
0
0
0
0
0
50
20
20
20
10
10
10
10
60
25
25
25
25
25
25
25
400
200
260
160
83
0
0
0
10
0
0
0
5.0
5.0
7.5
7.5
10
20
0
0
0
5
110
42
0
0
0
10
0
63
a
Number-average diameter determined by DLS. All DLS measure-
The expectation from the preceding experimental design was
supported by DLS measurements. The volume average of “large
NPs” in the presence of 70 nm SiO2 particles showed a
significant increase in size after irradiation, with Dv increasing to
∼260 nm (Figure S4 in the Supporting Information; Dn
increased to 230 nm). Since the diameter measured by DLS
is an “equivalent spherical” (or “same-size sphere”) diameter,27
such a size increase corresponds to close to a monolayer of 70
nm SiO2 NPs assembled on the BPS NPs. The volume ratio
between “large NPs” and SiO2 NPs showed an over-
representation of the former in both mixtures and thus is less
representative of the difference between the irradiated and non-
irradiated mixtures. SEM images of a better “visualized”
example obtained by using larger 1P NPs is presented in
Figure 2.
ments gave a polydispersity index (PDI) of <0.09, suggesting
monodisperse NPs.
Suspensions of dialyzed carbamate-BPS NPs were irradiated
with a hand-held UV lamp (4 mW/cm2 of 254 nm UV light).
Little change in particle size was observed by dynamic light
scattering (DLS), and the ζ potential was reversed from
negative to positive upon irradiation (Scheme 1 and Figure 1a).
Scheme 1. Light-Triggered Charge Reversal and Chemistry
of 1P NPs
Figure 2. SEM image of centrifuged, resuspended, and dried mixture
suspension of 1P (260 nm) and SiO2 NPs (70 nm) (a) before and (b)
after UV irradiation. Scale bar: 1 μm.
Figure 1. (a) ζ potential measurements of suspensions of 1P NPs after
UV irradiation for various durations. 1P NPs of various sizes generally
gave nearly identical results. (b) IR spectra of 1P and 1P-i NPs with
various durations of UV irradiation in water suspension.
The light-triggered self-assembly phenomenon could also be
applied in the formation of a bulk nanocomposite hydrogel
(Scheme 3). A mixture containing 1P NPs (Dn = 42 nm) and
poly(acrylic acid) (pAAc, MW = 1.0 × 106, pH adjusted to 8.1
by KOH) appeared as a viscous fluid. With UV irradiation, the
mixture turned into a nanocomposite hydrogel that was soft but
held its own weight and kept its shape even after being stored
upside down for more than 2 weeks (Figure 3). This is
This experiment showed that 10 min of UV irradiation with a
hand-held UV lamp was sufficient for reversal of the colloidal
charge. This was confirmed by the IR spectra of 1P and 1P-i
NPs drop-coated on a CaF2 plate. Samples prepared from
suspensions of 1P exhibited absorptions at 1698 cm−1 (CO)
and 1530 cm−1 (NO2). After irradiation for 10 min or longer,
these absorptions were no longer detectable (Figure 1b).
An application of light-triggered colloidal charge reversal was
demonstrated by the triggered self-assembly of nanomaterials.
A suspension of 1P (with number- and volume-average
diameters Dn = 160 nm and Dv = 200 nm, respectively) and
Scheme 3. Light-Triggered “Nanocomposite Hydrogel”
Assembly
SiO NPs (70 nm, prepared by the published Stober process)
̈
2
was prepared by mixing deionized water suspensions of the two
types of NP. We expected that without UV irradiation, the
negatively charged BPS NPs and SiO2 NPs would show little
affinity for each other. However, upon UV irradiation, the BPS
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of materials for cell and tissue experiments is under
investigation.
Hydrogel NPs (PA+74) remained suspended in the
supernatant under centrifugation while BPS NPs were
deposited as a solid. This difference was utilized to visualize
the light-triggered release. Without irradiation, the SEM image
of the NP complex collected by centrifugation showed organic
PA+74 NPs collected along with 1P NPs. Following light-
triggered release, the image suggested that PA+74 was no
longer associated with 1P-i (Figure 4). An experiment using
Figure 3. Photograph of a mixture of 1P NPs (Dn = 42 nm) and
aqueous pAAc (K+ salt), stored as shown for 14 days after UV
irradiation.
attributed to cross-linking of the linear polyanion by the
positively charged 1P-i NPs (converted from negatively
charged 1P NPs) through charge interactions. It is also
noteworthy that the total non-water mass percent in the
hydrogel network was ∼0.2%. An optimized version of the
nanocomposite hydrogel may exhibit properties such as high
mechanical toughness and self-healing17 and provide applica-
tions in fields such as tissue engineering28 and catalytic
hydrogels.29 These applications are currently under inves-
tigation.
Figure 4. SEM images of centrifuged, resuspended, and dried 1P NPs
(Dn = 160 nm) assembled with PA+74 NPs (a) without and (b) with
UV irradiation in H2O suspension. The dark region in (a) is dried PA
+74 (lightly cross-linked hydrogel) NPs (Figure S6).
The triggered release of functional NPs could also be
accomplished by the BPS NPs with light-triggered charge-
reversal capability. (Scheme 4) “PA+74” NPs (74 nm, ζ
fluorescence-labeled PA+74 NPs confirmed this observation.
The hydrogel NPs were released into water as a stable
suspension after the light-triggered release. With UV
irradiation, far more fluorescent hydrogel NPs stayed in the
supernatant rather than being removed by centrifugation with
1P NPs, providing the supernatant with higher fluorescence
intensity (Figure 5).
Scheme 4. Light-Triggered Release of “Plastic Antibody”
NPs
potential = +37
7 mV) belong to a family of therapeutic
polymer hydrogel NPs with antibody-like affinity for
peptides.30,31 1P (Dn = 160 nm) was slowly added into a
suspension of PA+74 NPs. After mixing and sonication, the
suspension consisted of 1P NPs loaded with PA+74 NPs in
excess. We expected that charge reversal of 1P NPs induced by
UV irradiation would trigger release of the PA+74 NPs by
charge repulsion.
The expectation from this experimental design was
supported by DLS data. The size of 1P NPs loaded with PA
+74 (Dn = 255 nm, Dv = 340 nm; minor aggregation among
multiple 1P and PA+74 NPs may have occurred during the
loading process) showed a significant decrease after irradiation
(Figure S6; Dn = 201 nm, Dv = 238 nm). The volume
contributed by PA+74 NPs, although underrepresented by
DLS in both samples, also increased from 31% in the non-
irradiated sample to 37% in the irradiated sample. Overall, the
size distribution difference between the irradiated and non-
irradiated mixtures suggests that the release of PA+74 NPs
from the surface of 1P NPs triggered by UV irradiation takes
place with significant efficiency. This experiment suggests the
possibility of triggered release of therapeutic NPs. Optimization
Figure 5. Fluorescence spectrum (λex = 330 nm) of the supernatant
after a centrifugation that removed 1P loaded with PA+74 NPs from
the suspension (blue). The 1P−PA+74 assembly was isolated from
the excess PA+74 prior to the experiment. The same sample was then
redispersed, UV-irradiated, and centrifuged, and the fluorescence
spectrum of the resulting supernatant was taken (pink).
In this research, we have demonstrated the first amine-free
modified Stober synthesis of uniform bridged polysilsesquiox-
̈
ane NPs (and size control strategies), the design and synthesis
of photoresponsive organic−silica hybrid NPs, and their
function of light-triggered charge reversal. We have also
accomplished light-triggered NP self-assembly, nanocomposite
hydrogel formation, and NP release based on the light-triggered
charge reversal of the BPS NPs. Our strategy and materials have
been shown to be compatible with organic or inorganic, soft or
rigid NPs as well as linear polymers. Thus, this research reveals
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(20) Guo, S.; Huang, Y.; Jiang, Q.; Sun, Y.; Deng, L.; Liang, Z.; Du,
Q.; Xing, J.; Zhao, Y.; Wang, P. C.; Dong, A.; Liang, X. J. ACS Nano
2010, 4, 5505−5511.
a novel strategy for nanoscale manipulation with good potential
for applications that include controlled formation of nano-
structured materials and nanocomposites as well as release of
polymer and NP drugs.
(21) Han, G.; You, C. C.; Kim, B. J.; Turingan, R. S.; Forbes, N. S.;
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ASSOCIATED CONTENT
(22) Vivero-Escoto, J. L.; Slowing, I. I.; Wu, C. W.; Lin, V. S. J. Am.
Chem. Soc. 2009, 131, 3462−3463.
■
S
* Supporting Information
(23) Hoshino, Y.; Kodama, T.; Okahata, Y.; Shea, K. J. J. Am. Chem.
Soc. 2008, 130, 15242−15243.
Detailed synthesis and characterization data as well as
experimental procedures and data supporting the statements
about the function of materials. This material is available free of
charge via the Internet at http://pubs.acs.org.
(24) Nederberg, F.; Zhang, Y.; Tan, J. P.; Xu, K.; Wang, H.; Yang, C.;
Gao, S.; Guo, X. D.; Fukushima, K.; Li, L.; Hedrick, J. L.; Yang, Y. Y.
Nat. Chem. 2011, 3, 409−414.
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AUTHOR INFORMATION
4303−4313.
■
(26) Singh-Gasson, S.; Green, R. D.; Yue, Y.; Nelson, C.; Blattner, F.;
Corresponding Author
kjshea@uci.edu
Sussman, M. R.; Cerrina, F. Nat. Biotechnol. 1999, 17, 974−978.
(27) Schartl, W. Light Scattering from Polymer Solutions and
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Notes
Nanoparticle Dispersions; Springer: Berlin, 2007.
The authors declare no competing financial interest.
(28) Chang, C. W.; van Spreeuwel, A.; Zhang, C.; Varghese, S. Soft
Matter 2010, 6, 5157−5164.
(29) Das, A. K.; Collins, R.; Ulijn, R. V. Small 2008, 4, 279−287.
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ACKNOWLEDGMENTS
■
We thank Lawrence Livermore National Laboratory for support
of this research. L.-C.H. is also grateful for a graduate fellowship
from Lawrence Livermore National Laboratory. We also thank
Dr. Philip R. Dennison, Jorge Meyer, and Matthew Sullivan for
NMR, glass, and SEM techniques.
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