NANO

LETTERS

Hydrophobic Nanocrystals Coated with

an Amphiphilic Polymer Shell: A
General Route to Water Soluble
Nanocrystals

2004
Vol. 4, No. 4
703-707

Teresa Pellegrino,, Liberato Manna,*,, Stefan Kudera, Tim Liedl,

Dmitry Koktysh, Andrey L. Rogach, Simon Keller, Joachim Ra1 dler,
Giovanni Natile, and Wolfgang J. Parak*,
Department of Physics & Center for Nanoscience, Ludwig-Maximilians UniVersitat
Munchen, Munchen, Germany, Department of Chemistry and Pharmacology,
UniVersity of Bari, Bari, Italy, and National Nanotechnology Lab of INFM,
Via Arnesano, Lecce, Italy
Received December 12, 2003; Revised Manuscript Received February 9, 2004

ABSTRACT
A general strategy is described which allows for transferring hydrophobically capped nanocrystals from organic to aqueous solution by
wrapping an amphiphilic polymer around the particles. In particular, high quality CoPt3, Au, CdSe/ZnS, and Fe2O3 nanocrystals have been
water-solubilized in this way. Analysis with transmission electron microscopy, gel electrophoresis, and fluorescence correlation spectroscopy
demonstrates that monodispersity of the particles is conserved upon phase transfer to aqueous solution.

Introduction. Colloidal inorganic nanocrystals are promising

materials because of their unique size-dependent properties.1-3
For many materials nanocrystals can be either synthesized
in aqueous solution (e.g., Au,4 CdTe and CdSe,5 Fe3O4 6) or
in organic solvents (e.g., Au,7 CdTe and CdSe,8 Fe3O4 9).
However, for some materials such as Co10 or for improved
shape control,11 highly crystalline and monodisperse nanocrystals so far need to be synthesized in organic solvents at
high temperature. This involves their surface to be coated
with surfactants that render them hydrophobic.12 Several
methods exist for converting hydrophobic nanocrystals into
hydrophilic particles, which is a prerequisite for biological
applications.13-16 Most methods rely on the exchange of the
surfactant coating with ligand molecules that on one end
carry a functional group that is reactive toward the nanocrystal surface and on the other end a hydrophilic group (see,
for example, refs 13, 17-19). Appropriate ligand molecules
have to be individually chosen for each material. Therefore,
other strategies have been developed which, instead of
exchanging the original hydrophobic surfactant layer with a
hydrophilic one, are based on the addition of a second ligand
layer. The second layer consists of amphiphilic molecules
* Corresponding authors. E-mail: liberato.manna@unile.it; wolfgang.
parak@physik.uni-muenchen.de
Ludwig-Maximilians Universita
t Munchen, Germany.
University of Bari, Italy.
National Nanotechnology Lab of INFM, Lecce, Italy.
10.1021/nl035172j CCC: $27.50
Published on Web 03/26/2004

2004 American Chemical Society

that can intercalate the first hydrophobic surfactant layer with

their hydrophobic portion and that ensure water solubility
of the nanocrystal with their hydrophilic groups. Interdigitated bilayers have been formed, for instance, by the addition
of n-alcanoic acids20 or cetyltrimethylammonium bromide.21
Alternatively, cyclodextrin has been used for the formation
of the second ligand layer, whereby the hydrophobic cavity
of the cyclodextrin is penetrated by the hydrophobic tails of
the first layer and its hydrophilic surface is pointing toward
the solution.22,23 In these examples, the second layer is solely
stabilized around the first layer by hydrophobic interactions.
For improved stability a method has been suggested recently
to coat hydrophobic CdSe/ZnS nanocrystals with a crosslinked amphiphilic polymer,24 in which the hydrophobic tails
of the polymer intercalate with the surfactant molecules of
the nanocrystal and form an additional coating. The water
solubility of the polymer-coated nanocrystals is ensured by
the hydrophilic groups located on the outer region of the
polymer shell. Finally, the polymer shell is stabilized by
cross-linking.
Based on this scheme we have developed a simple and
general strategy for decorating hydrophobic nanocrystals of
various materials (CoPt3,25 Au,7 CdSe/ZnS,26 and Fe2O3 27)
with a hydrophilic polymer shell by exploiting the nonspecific hydrophobic interactions between the alkyl chains of
poly(maleic anhydride alt-1-tetradecene) and the nanocrystal

Scheme 1.

Polymer Coating of the Nanocrystals

Scheme of the polymer coating procedure. Several reports (e.g. ref 35) suggest that the surfactant chains for hydrophobically capped
nanocrystals are pointing away from the nanocrystal surface, in a brush-like arrangement. The following plausible configuration is then
assumed for the polymer coating process: The hydrophobic alkyl chains of the polymer intercalate with the surfactant coating. The anhydride
rings are located on the surface of the polymer-coated nanocrystal. The amino end groups of the cross-linker molecule open the rings and
link the individual polymer chains. The surface of the polymer shell becomes negatively charged, stabilizing the particles in water by
electrostatic repulsion. A structural analysis aimed at determining the detailed conformation of the cross-linked polymer shell is in progress.

surfactant molecules. Addition of bis(6-aminohexyl)amine

results in the cross-linking of the polymer chains around each
nanoparticle (Scheme 1). The nanocrystals become soluble
in water upon hydrolyzation of the unreacted anhydride
groups (which effectively leads to an amphiphilic polymer
shell) and can be further processed according to a universal
protocol that relies solely on the chemistry of the outer
polymer shell.
Experimental Details. Poly(maleic anhydride alt-1-tetradecene) was purchased from Aldrich and had a number
average molecular weight (Mn) 7300, corresponding to
roughly 25 monomer units per polymer chain, and a
monodispersity value (Mn/Mw) equal to 1.23, as declared
by the vendor. Such polymer becomes amphiphilic upon
hydrolyzation of the anhydride functional groups. A solution
of poly(maleic anhydride alt-1-tetradecene) in chloroform
and a solution of monodisperse nanocrystals in chloroform
(100 polymer units per nm2 of nanocrystal surface) were
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mixed and stirred for 2 h at room temperature. After

evaporation of the solvent, bis(6-aminohexyl)amine in
chloroform was then added to cross-link the polymer shell
that had formed around each nanocrystal. The ratio of added
cross-linker molecules to polymer units was 1:10. The
solution was sonicated for 20 min, the solvent was evaporated
again, and the solid was dissolved in a diluted TBE buffer
solution (pH 8-9). After sonicating for five minutes, the
nanocrystals dissolved completely and the solution was
filtered to remove the excess unbound polymer. The buffer
was exchanged with water by two rounds of dilution and
reconcentration through a centrifuge filter. Any residual
unbound polymer was removed by two consecutive purification steps on a size-exclusion column. After purification the
nanocrystals solutions were optically clear. The particles were
characterized by transmission electron microscopy (TEM),
gel electrophoresis, and fluorescence correlation spectroscopy
(FCS). The solutions were stable for months (i.e., no
Nano Lett., Vol. 4, No. 4, 2004

Figure 1. TEM images of polymer-coated nanocrystals of four different core materials: Fe2O3 (9.2 nm average diameter), Au (4.0 nm),
CoPt3 (8.0 nm), and CdSe/ZnS (7.0 nm) nanocrystals.

precipitation occurred and the bands during gel electrophoresis kept their narrow shape).
Results and Discussions. In water the nanocrystals
retained their major physical properties (such as the fluorescence of CdSe/ZnS and the magnetic moment of CoPt3).
TEM analysis (Figure 1) showed no large aggregates of
particles, besides the formation of monolayers. Such patterns
are due to particle-particle interactions (van der Waals,
magnetic) and are also observed on grids prepared from
solutions of hydrophobic nanocrystals. However, the presence
of small aggregates, such as dimers and trimers, cannot be
distinguished from such monolayers and so it cannot be
excluded.
The polymer-coated nanocrystals were investigated with
agarose gel electrophoresis28 (Figure 2). The bands on the
gels are remarkably narrow, and since the particle mobility
on gels depends on both charge and size, we estimated that
our polymer-coated particles have a rather homogeneous
Nano Lett., Vol. 4, No. 4, 2004

distribution of sizes and charges. The mobility of the

polymer-coated nanocrystals is comparable to that of phosphine stabilized Au particles,28 indicating that there is no
cross-linking between several particles. Any aggregates
should in fact migrate much slower through the gel. We can
estimate the sensitivity in assessing particle diameters by gel
electrophoresis by devising a calibration curve of the particle
mobility versus particle diameter, as reported in a previous
study.29 The study showed that the mobility of particles with
diameters between 3 and 20 nm scaled roughly linearly with
the particle diameter. In the present study, the band of 4.0
nm diameter polymer-coated gold nanoparticles (Figure 2)
has a spread of (0.03 if the mobility of the middle of the
band is normalized to 1, allowing us to distinguish between
particles with mobility of 1.0 and 0.97 (or 1.0 and 1.03),
respectively. From the calibration curve,29 a decrease in
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Figure 2. Gel electrophoresis of polymer-coated nanocrystals corresponding to the samples of Figure 1. The bands were observed either
by their fluorescence (CdSe/ZnS) or by their absorption color. For each sample the left lane (lanes 1, 3, 5, 7) corresponds to particles as
obtained after the last column purification step. The right lanes (lanes 2, 4, 6, 8) correspond to an additional purification step where the
fastest migrating band of nanocrystals in a first gel run has been extracted.

mobility of 0.03 corresponds to an increase in effective

particle diameter of only 1.2 nm, which cannot be due to an
aggregation effect between particles having an average
diameter of 4.0 nm. Any significant interparticle agglomeration, if present, would clearly cause a much larger band
spread. We conclude then that no significant agglomerates
are present. Only in the case of CdSe/ZnS nanocrystals could
a small amount of aggregates be seen, since the gel
electrophoresis bands showed slow migrating tails (Figure
2, lane 1). However, after extracting the fastest migrating
band and rerunning it with gel electrophoresis, these aggregates were removed (Figure 2, lane 2). In the case of
Fe2O3, CoPt3, and Au, no remarkable band tails were present
already after the first run. It is worth noting that in this second
run no stripping of the polymer shell from the particles was
observed in any sample, since no tail of particles with
reduced mobility was found. This is an indication that the
polymer layer that formed around the nanocrystals is
significantly stable.
To get an estimate of the effective particle diameter in
solution we used fluorescence correlation spectroscopy
(FCS)30,31 (see Supporting Information). For green and red
fluorescent hydrophobic CdSe/ZnS particles dissolved in
chloroform, we obtained hydrodynamic diameters of 5.7 (
0.5 nm and 11.6 ( 2.8 nm, respectively. After the polymer
coating procedure, hydrodynamic diameters of 19.2 ( 2.0
nm and 23.6 ( 2.0 nm, respectively, were measured for the
particles dissolved in water. Clearly an increase in size due
to the formation of the polymer shell could be observed, but
this is larger than expected if one considers only the
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contribution from the polymer layer. The significant increase

in the hydrodynamic diameter as determined from FCS
measurements could partly result from the change in
particle-solvent interaction, although the formation of small
aggregates as dimers or trimers cannot be excluded.
Considering the TEM, gel electrophoresis, and FCS results,
it seems that no significant interparticle cross-linking occurs
during the synthesis. The minimization of interparticle
aggregation during the polymer coating procedure has been
achieved by working with enough diluted solutions (see
Supporting Information).
Conclusions. The described procedure for transferring
hydrophobic nanocrystals into aqueous solution should be
extendable to any nanocrystal system in which hydrophobic
tails are exposed to the external environment. For example,
it has also been successfully applied to as complex objects
as CdTe tetrapods32 (data not shown). This method therefore
is quite general and could be extended to systems for which
phase transfer to aqueous solution has not been possible so
far with other methods. In principle, the polymer shell could
be further improved regarding its functional groups and its
stability. Incorporation of poly(ethylene glycol) groups, for
example, should improve the stability in electrolytic solution
(such as making the solubility of nanocrystals less dependent
on electrostatic repulsion) and should also minimize nonspecific interactions.
One promising application of the polymer-coated nanocrystals could be the construction of DNA-mediated hybrid
materials,33 such as for instance the formation of dimers
between fluorescent CdSe/ZnS and magnetic CoPt3 nanoNano Lett., Vol. 4, No. 4, 2004

crystals. One requisite for this goal is to precisely control

the number of biological molecules (as oligonucleotides) that
are attached per particle.28,34
The strategy described here yields particles with different
intrinsic properties (such as fluorescence or magnetism) but
identical surface chemistry and with good homogeneity in
charge and size. These nanocrystals then should be promising
candidates for the controlled fabrication of more sophisticated
nanoscale structures.
Acknowledgment. The authors are grateful to Dr. Elena
Shevchenko, Dr. David Gittins, and Eric Dulkeith for help
with the cobalt-platinum and the gold syntheses, to Monika
Rusp for the assistance in TEM measurements, and to Prof.
Dr. Hermann Gaub, Dr. Markus Seitz, Prof. Dr. Jochen
Feldmann, and Prof. Dr. Roberto Cingolani for helpful
suggestions. This work was funded by the Emmy Noether
program of the German research foundation DFG (W.J.P.),
the Fonds der Deutschen Chemischen Industrie (W.J.P.), and
was also supported by the Center for Nanoscience in Munich
and by the Italian INFM-NNL and FIRB funds. T.P. is
grateful to Marie Curie training program of the European
Union, and D.K. is grateful to the Alexander von Humboldt
Foundation. Travel costs between Germany and Italy were
in part supported by the Vigoni foundation/Deutscher Akademischer Austauschdienst (DAAD).
Supporting Information Available: Description of the
various nanocrystal syntheses and polymer coating procedures, gel electrophoresis, and fluorescence correlation
spectroscopy setups. This material is available free of charge
via the Internet at http://pubs.acs.org.
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