Gold nanoparticles coated with semi-fluorinated oligo(ethylene glycol) produce sub-100 nm nanoparticle vesicles without templates

Article abstract of DOI:10.1021/ja302122w

Gold nanoparticles (NPs) with diameters of 5, 10, and 20 nm coated with semifluorinated oligo(ethylene glycol) ligands were formed into sub-100 nm hollow NP assemblies (NP vesicles) in THF without the use of a template. The NP vesicles maintained their st

Full text of DOI:10.1021/ja302122w

Communication
pubs.acs.org/JACS
Gold Nanoparticles Coated with Semi-Fluorinated Oligo(ethylene
glycol) Produce Sub-100 nm Nanoparticle Vesicles without
Templates
,†
‡
§
‡
§
∥
Kenichi Niikura,* Naoki Iyo, Takeshi Higuchi, Takashi Nishio, Hiroshi Jinnai, Naoki Fujitani,
and Kuniharu Ijiro†,⊥
†
Research Institute for Electronic Science (RIES), Hokkaido University, Kita 21, Nishi 10, Kita-Ku, Sapporo 001-0021, Japan
Graduate School of Chemical Sciences and Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-Ku, Sapporo 060-8628, Japan
Institute for Materials Chemistry and Engineering (IMCE) and Japan Science and Technology Agency (JST), ERATO, Takahara
‡
§
Soft Interfaces Project, CE 80, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
∥
Graduate School of Advanced Life Science, Frontier Research Center for Post-Genome Science and Technology, Hokkaido
University, Sapporo, Japan
⊥
CREST, Japan Science and Technology Agency (JST), Sanban-cho 5, Chiyoda-ku, Tokyo 102-0075, Japan
S Supporting Information
*
10
core to assemble NPs, the inner space might not be sufficient
to enclose drugs.
ABSTRACT: Gold nanoparticles (NPs) with diameters
of 5, 10, and 20 nm coated with semifluorinated
oligo(ethylene glycol) ligands were formed into sub-100
nm hollow NP assemblies (NP vesicles) in THF without
the use of a template. The NP vesicles maintained their
structure even after the solvent was changed from THF to
other solvents such as butanol or CH Cl . NMR analyses
indicated that the fluorinated ligands are bundled on the
NPs and that the solvophobic feature of the fluorinated
bundles is the driving force for NP assembly. The formed
NP vesicles were surface-enhanced Raman scattering-
active capsules.
To utilize the cavity in NP vesicles, the development of
alternative assembly approaches that do not use a template is
important. Stucky and co-workers reported the one-pot
synthesis of NP vesicles using polyamine and negatively
11
charged quantum dots. Recently, the codisplay of hydro-
2
2
phobic and hydrophilic ligands on the surface of NPs provided
an amphiphilic feature to NPs, inducing their self-assem-
12−14
bly.
Kumacheva and co-workers reported the vesicular
assembly of hydrophilic cetyltrimethylammonium bromide
CTAB)-coated gold nanorods by partial modification with
(
12
hydrophobic polystyrene. The coating of gold NPs (AuNPs)
with hydrophobic poly(methyl methacrylate) (PMMA) and
hydrophilic poly(ethylene glycol) (PEG) has also been
nterparticle plasmonic coupling in an assembly produces
collective properties different from those of the dispersed
13
reported to result in the formation of NP vesicles. However,
I
there have been few reports of NP vesicles with sub-100 nm
diameters constructed using these self-assembly approaches.
Herein we demonstrate that surface modification with a
single molecule, a semifluorinated ligand (SFL), can efficiently
produce sub-100 nm NP vesicles (∼60 nm in diameter) in
tetrahydrofuran (THF) solution. The newly synthesized SFLs
were composed of three parts: oligo(ethylene glycol) (OEG),
fluorinated tetraethylene glycol (FG), and an 11-carbon alkyl
chain with a thiol terminus (Scheme 1). This approach is based
on simple one-pot ligand modification and was found to be
applicable to AuNPs with diameters of 5, 10, and 20 nm. We
believe that the important feature of this work is the
preparation of NP vesicles using a homogeneous small surface
ligand instead of multiple different polymers as in previous
reports. The coating with small molecules allows the gaps
between the NPs to be significantly decreased, expanding the
plasmonic application of the NP vesicles. To emphasize these
merits, we demonstrate that NP vesicles can be used as a
particles; therefore, metal and semiconductor nanoparticle
(
NP) assemblies are of considerable interest in many fields,
1
−3
such as materials, analytical, and medical sciences.
vesicular assembly of NPs (NP vesicles), in particular, will
provide new applications for NPs through utilization of the
inner space for drug delivery systems, catalyst carriers, surface-
enhanced Raman scattering (SERS) sensing platforms, and so
on. In particular, for drug delivery carriers, such as micelles, a
diameter of <100 nm is known to be important for targeting
tumor cells. To extend such applications, a new approach to
the assembly or organization of NPs must be developed. As a
conventional approach for the construction of NP vesicles,
templates have been often used. For example, emulsion drops,
known as Pickering emulsion, have been used to assemble NPs
at the liquid−liquid interface. In many cases, the emulsion-
drop-templated method gives micrometer-sized NP vesicles.
The
4
5
6
7
8
Liposomes have also been used as templates to produce NP
vesicles; however, the size of the NPs that can be embedded in
9
lipid bilayers is limited to <6 nm, which makes plasmonic
applications difficult. When template molecules are used as a
Received: March 3, 2012
Published: April 25, 2012
©
2012 American Chemical Society
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Communication
Scheme 1. Structure of the SFL Used in This Study and Self-
Assembly of SFL-AuNPs to Generate NP Vesicles
obtained by inductively coupled plasma optical emission
spectroscopy (ICP-OES) (Table S1). This number corre-
sponds to a 1:2 molecular ratio of ligands to surface Au atoms,
16
indicating almost complete ligand coverage. SEM showed the
efficient formation of spherical assemblies of NPs (Figure 1).
The average diameter of the NP vesicles as judged from the
SEM images (300 counts) was 65 nm for 10 nm AuNPs, and
the size distribution was relatively narrow. Dynamic light
scattering measurements also confirmed this, giving an
assembly size of ∼68 nm in THF solution (Figure S2). In
addition to the 10 nm AuNPs, AuNPs with diameters of 5 and
2
0 nm also formed NP vesicles (Figure 1c,d). The average
diameter of the vesicles increased with increasing size of the
NPs (60 and 95 nm for 5 and 20 nm AuNPs, respectively).
Transmission electron microscopy (TEM) images indicated the
characteristic hollow structures with high contrast between the
shell and the interior (Figure 1e).
platform for optically enhanced spectroscopies such as SERS in
solution because of the close packing of the NPs.
SFL-coated AuNPs (SFL-AuNPs) were synthesized through
ligand exchange from citric acid to SFLs in THF. SFLs in THF
(
2 mM, 1 mL) were added to an aqueous solution (20 μL) of
Transmission electron microtomography (TEMT) was used
to probe the three-dimensional (3D) structure of the NP
assemblies. NP vesicles made from 5 nm AuNPs were
embedded in epoxy resin (Epok-812) by curing at 60 °C for
12 h. Thin-film sections of this epoxy resin were prepared using
an ultramicrotome (Leica Ultracut UCT). The sections were
transferred on a Cu grid with a poly(vinyl fluoride) (PVF)
supporting membrane. A series of TEM images were acquired
at 1° tilt intervals from −73.6 to 75.8°. The tilt-series images
were aligned with a fiducial marker method using AuNPs as the
fiducial markers and then reconstructed using the filtered-back-
projection (FBP) method. A series of images sliced along the
XY plane for the same specimen area at various height positions
are shown in Figure 2a. In these images, the spherical dark
regions correspond to the AuNPs, and the assembly (indicated
by the black arrow) was reconstructed. The 3D image of the
assembly clearly shows the hollow spherical structures of the
NP vesicles composed of a single layer of AuNPs (Figure 2b).
To clarify the mechanism of NP vesicle formation, we
increased the number of terminal ethylene glycol units of the
citric acid-coated AuNPs (10 nm diameter) and purified by
repeated centrifugation. The AuNP solution changed from red
to purple soon after mixing of the AuNPs and SFLs, indicating
that AuNP assemblies were formed in the solution. UV−vis
spectral analysis showed that the surface plasmon resonance
band of the NP vesicles displayed a 30 nm red shift relative to
that of dispersed dodecanethiol-coated AuNPs in THF (Figure
S1 in the Supporting Information), supporting our assumption
that AuNP assemblies were formed in the solution. The
interparticle distance was estimated to be 2.5 nm from the
scanning electron microscopy (SEM) image. This interparticle
distance was also supported by the shift in the plasmon peak. In
the case of a 10.5 nm AuNP superlattice, a plasmon shift of 30
nm was reported for an interparticle gap of 2.3 nm, which is
in good agreement with our results. The length of the linear
form of the SFL is calculated to be ∼3.6 nm; therefore,
interdigitation of the ligands should occur in the interparticle
gap (see Figure 3d). The ligand coverage on a single AuNP was
calculated to be 58.1% on the basis of the S/Au molar ratio
17
15
Figure 1. (a−d) SEM images of NP vesicles made from (a, b) 10, (c) 5, and (d) 20 nm SFL-AuNPs. (e) TEM image of an NP vesicle made from 10
nm SFL-AuNPs.
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Journal of the American Chemical Society
Communication
Figure 2. (a) Reconstructed images (XY plane) of NP vesicles embedded in epoxy resin. (b) 3D structures of NP vesicles as indicated by the black
arrow in (a). Scale bars are 50 nm.
SFLs from 2 to 3 or 4. This increase did not affect the vesicular
assemblies; however, SFLs without OEG or a fluorinated
segment did not produce AuNP vesicular assemblies (Figure
S3), indicating that both segments are essential for the
formation of NP vesicles. Importantly, these NP vesicles
could be observed only when the ligand exchange was carried
out in THF. We examined many general solvents, such as H O,
2
methanol, butanol, ethyl acetate, acetone, toluene, dichloro-
methane, and hexane; however, no NP vesicle formation was
observed. Thus, the solubility of the terminal OEG and FG
segments in THF is an important factor in the NP assembly.
NMR spectroscopy is one of the most powerful methods for
1
8
examining the structure of ligands immobilized on NPs.
1
Figure 3 shows the H NMR spectra of free SFLs in methanol-
d and SFL-AuNPs in methanol-d and THF-d . The sharp,
4
4
8
characteristic NMR spectrum (Figure 3b) indicates the unique
molecular motion of SFLs linked to the AuNPs. The protons of
the terminal OEG segment (peak f) were observed as sharp
signals, whereas the protons adjacent to the FG segment (peak
e) disappeared because of significant line broadening. This
suggests that the OEG segments on AuNPs were directly
accessible to the solvent with high flexibility, similar to those in
the free-form SFLs in methanol. At the same time, the motion
of the FG segments was significantly suppressed, as shown by
the disappearance of peak e, indicating that the FG segments
contribute to the bundle formation (Figure 3d). In THF, the
SFL-AuNPs displayed a significantly broadened spectrum.
Protons derived from both the OEG and FG segments were
not detected, although the signal corresponding to the alkyl
chain protons (peak c) was apparent, indicating that the motion
of the terminal OEG segment and the FG segment was
drastically suppressed in THF. We propose that the
solvophobic feature of the FG segment is the main driving
force behind the NP assembly (Figure 3d). In fact, fluorinated
1
Figure 3. H NMR spectra of (a) free SFLs in methanol-d , (b) SFL-
4
AuNPs in methanol-d , and (c) SFL-AuNPs in THF-d . * represents
signals derived from solvents. (d) Schematic presentation of SFLs on
AuNPs in THF.
4
8
showed a ζ potential of −7.8 mV. This electrostatic repulsion
would stabilize monolayer formation by preventing layering of
the NPs. The sharpness of the alkyl chain peak c in THF means
that the alkyl chains are partially exposed to THF, which is a
good solvent for alkyl chains. This solubility of the alkyl
segment is also thought to contribute to the stable dispersibility
19
compounds are known to demonstrate a solvophobic feature.
In addition, especially in THF, OEG aggregation may also assist
vesicule formation. PEG derivatives tend to aggregate in
2
0
THF. To stabilize the NP vesicles, electrostatic repulsion
21
between the NPs is thought be important. SFL-coated AuNPs
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Journal of the American Chemical Society
Communication
of the NP vesicles in THF. In addition to 1H NMR
measurements, 19F NMR measurements were also performed
to analyze the FG segments directly. As in H NMR spectra,
(2) Jones, M. R.; Osberg, K. D.; Macfarlane, R. J.; Langille, M. R.;
Mirkin, C. A. Chem. Rev. 2011, 111, 3736.
(3) Li, F.; Josephson, D. P.; Stein, A. Angew. Chem., Int. Ed. 2011, 50,
1
3
60.
4) (a) Yang, X. C.; Samanta, B.; Agasti, S. S.; Jeong, Y.; Zhu, Z. J.;
Rana, S.; Miranda, O. R.; Rotello, V. M. Angew. Chem., Int. Ed. 2011,
0, 477. (b) Sanson, C.; Diou, O.; Thevenot, J.; Ibarboure, E.; Soum,
A.; Brulet, A.; Miraux, S.; Thiaudiere, E.; Tan, S.; Brisson, A.; Dupuis,
fluorine signals derived from free SFLs were clearly observed in
THF-d and methanol-d (data not shown), whereas those of
(
8
4
SFL-AuNPs were not detected in either solvent, supporting our
assumption that the solvophobic feature of the FG segments
contributes to the formation of the NP vesicles.
5
́
̀
V.; Sandre, O.; Lecommandoux, S. ACS Nano 2011, 5, 1122.
Interestingly, the vesicle structures formed in THF were
maintained even after dispersion into different solvents,
including nonpolar (CH Cl ethyl acetate) and polar (butanol)
(5) Yang, M.; Alvarez-Puebla, R.; Kim, H. S.; Aldeanueva-Potel, P.;
́
Liz-Marzan, L. M.; Kotov, N. A. Nano Lett. 2010, 10, 4013.
(6) Cabral, H.; Matsumoto, Y.; Mizuno, K.; Chen, Q.; Murakami, M.;
Kimura, M.; Terada, Y.; Kano, M. R.; Miyazono, K.; Uesaka, M.;
Nishiyama, N.; Kataoka, K. Nat. Nanotechnol. 2011, 6, 815.
2
2,
solvents (Figure S4), indicating the stability of the spherical
morphology. Using Monte Carlo simulations, Kegel and co-
workers demonstrated that a hollow shell composed of
individual NPs made on a template is intrinsically stable even
(
(
7) Pickering, S. U. J. Chem. Soc., Trans. 1907, 91, 2001.
8) (a) Dinsmore, A. D.; Hsu, M. F.; Nikolaides, M. G.; Marquez, M.;
Bausch, A. R.; Weitz, D. A. Science 2002, 298, 1006. (b) Saigal, T.;
Dong, H.; Matyjaszewski, K.; Tilton, R. D. Langmuir 2010, 26, 15200.
c) Nie, Z.; Park, J. I.; Li, W.; Bon, S. A. F.; Kumacheva, E. J. Am.
Chem. Soc. 2008, 130, 16508. (d) Thompson, K. L.; Armes, S. P.;
Howse, J. R.; Ebbens, S.; Ahmad, I.; Zaidi, J. H.; York, D. W.; Burdis, J.
A. Macromolecules 2010, 43, 10466.
(9) Rasch, M. R.; Rossinyol, E.; Hueso, J. L.; Goodfellow, B. W.;
Arbiol, J.; Korgel, B. A. Nano Lett. 2010, 10, 3733.
21
after removal of the template. Our data appear to support the
results of these simulations and the general utility of NP
vesicles in various organic solvents. In water, however, the NP
vesicles were not dispersed but rather were aggregated.
SERS enhancement is one of the attractive applications for
NP vesicles, as dispersed vesicles are suitable for direct SERS
detection of analytes in solution. In the presence of the NP
vesicles, SERS signals from crystal violet were clearly observed,
whereas in the case of dispersed AuNPs, no signals were
observed (Figure S5), indicating that NP vesicles can act as a
platform for Raman-based sensing in solutions.
(
(
10) (a) Song, C.; Zhao, G.; Zhang, P.; Rosi, N. L. J. Am. Chem. Soc.
010, 132, 14033. (b) Hwang, L.; Zhao, G.; Zhang, P.; Rosi, N. L.
Small 2011, 7, 1939.
11) Cha, J. N.; Birkedal, H.; Euliss, L. E.; Bartl, M. H.; Wong, M. S.;
Deming, T. J.; Stucky, G. D. J. Am. Chem. Soc. 2003, 125, 8285.
12) Nie, Z.; Fava, D.; Kumacheva, E.; Zou, S.; Walker, G. C.;
2
(
In summary, we have found that AuNPs coated with
semifluorinated OEG ligands efficiently provide sub-100 nm
hollow NP assemblies in THF. The NP vesicles were SERS-
active in THF. Our approach was based on the unique function
of the fluorinated OEG region, which induces the bundling of
ligand molecules on NPs. This approach using a single OEG
derivative appears to be applicable to the construction of NP
vesicles from various kinds of colloidal particles. We are
currently exploring the chemical modification of AuNPs (such
as cross-linking) in NP vesicles to be utilized as plasmon-active
drug delivery carriers in aqueous solutions.
(
Rubinstein, M. Nat. Mater. 2007, 6, 609.
(13) Nikolic, M. S.; Olsson, C.; Salcher, A.; Kornowski, A.; Rank, A.;
Schubert, R.; Fromsdorf, A.; Weller, H.; Forster, S. Angew. Chem., Int.
Ed. 2009, 48, 2752.
(
14) Song, J.; Cheng, L.; Liu, A.; Yin, J.; Kuang, M.; Duan, H. J. Am.
Chem. Soc. 2011, 133, 10760.
15) Chen, C.-F.; Tzeng, S.-D.; Chen, H.-Y.; Lin, K.-J.; Gwo, S. J. Am.
Chem. Soc. 2008, 130, 824.
(
(16) Luedtke, W. D.; Landman, U. J. Phys. Chem. B 1998, 102, 6566.
(17) (a) Jinnai, H.; Spontal, R. J. Polymer 2009, 50, 1067. (b) Jinnai,
H.; Spontak, R. J.; Nishi, T. Macromolecules 2010, 43, 1675.
18) Badia, A.; Singh, S.; Demers, L.; Cuccia, L.; Brown, G. R.;
Lennoz, R. B. Chem.Eur. J. 1996, 2, 359.
19) Ishikawa, Y.; Kuwahara, H.; Kunitake, T. J. Am. Chem. Soc. 2004,
16, 5579.
20) (a) Gitsov, I.; Frec
b) Gitsov, I.; Wooley, K. L.; Frec
Engl. 1992, 31, 1200.
(21) Mani, E.; Sanz, E.; Bolhuis, P. G.; Kegel, W. K. J. Phys. Chem. C
010, 114, 7780.
(
ASSOCIATED CONTENT
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(
1
*
S
Supporting Information
Experimental details and supporting figures. This material is
available free of charge via the Internet at http://pubs.acs.org.
(
́
het, J. M. J. J. Am. Chem. Soc. 1996, 118, 3785.
het, J. M. J. Angew. Chem., Int. Ed.
(
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AUTHOR INFORMATION
■
2
Corresponding Author
kniikura@poly.es.hokudai.ac.jp
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
2
This work was supported by JST-CREST and KAKENHI
2655050: Grant-in-Aid for Challenging Exploratory Research.
A part of this work was conducted at Hokkaido Innovation
through Nanotechnology Support (HINTS), supported by the
“Nanotechnology Network JAPAN” Program of the Ministry of
Education, Culture, Sports, Science and Technotogy (MEXT),
Japan.
REFERENCES
■
(
1) Nie, Z.; Petukhova, A.; Kumacheva, E. Nat. Nanotechnol. 2010, 5,
15.
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