2340 Biomacromolecules 2004, 5, 2340-2346

Synthesis of Chitosan-Stabilized Gold Nanoparticles in the

Absence/Presence of Tripolyphosphate
Haizhen Huang and Xiurong Yang*
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry,
Chinese Academy of Sciences, Changchun Jilin 130022, P. R. China
Received May 14, 2004; Revised Manuscript Received July 23, 2004

Gold nanoparticles were prepared by reducing gold salt with a polysaccharide, chitosan, in the absence/
presence of tripolyphosphate (TPP). Here, chitosan acted as a reducing/stabilizing agent. The obtained gold
nanoparticles were characterized with UV-vis spectroscopy and transmission electron microscopy. The
results indicated that the shape and size distribution of gold nanoparticles changed with the molecular weight
and concentration of chitosan. More interestingly, the gelation of chitosan upon contacting with polyanion
(TPP) can also affect the shape and size distribution of gold nanoparticles. By adding TPP to chitosan
solution before the reduction of gold salt, gold nanoparticles have a bimodal size distribution, and at the
same time, polygonal gold particles were obtained in addition to spherical gold nanoparticles.

Introduction obtained by using different molecular weight chitosan as

Metal nanoparticles have attracted much attention for their
unusual chemical and physical properties, such as catalysis,
novel electronic, optic, and magnetic properties, and ap-
plication in biotechnology.1 The synthesis of nanoparticles
with different chemical composition, size distribution, and
controlled monodispersity is an important area of research
in nanotechnology. Concerning the synthesis of metal
nanoparticles, especially gold nanoparticles, many methods
have existed in the literature.2 In the latest several years,
biomolecules and bioorganisms were also used in the
synthesis of nanomaterials.3 A novel biological method for
the synthesis of gold and silver nanoparticles using the fungus
Verticillium was reported by Mukherjee et al. Exposure of
the fungal biomass to aqueous AuCl4- or Ag+ ions resulted
in the intracellular reduction of the metal ions and formation
of gold and silver nanoparticles of good monodispersity.4
Recently, Raveendran et al.5 reported the preparation of
starched silver nanoparticles using a reducing sugar, β-D-
glucose, as the reducing agent and starch as a capping agent,
which provided a method for “green” nanoparticle prepara-
tion.
Gold nanoparticles were prepared using many methods,
as indicated in this article. But to the best of our knowledge,
this is the first time use of a polysaccharide, chitosan, in the
synthesis of gold nanoparticles. Recently, Qi et al.6 reported
the synthesis of gold nanoparticles using sucrose, which is
another kind of sugar. Chitosan has been used as a protecting
agent by Esumi in preparation of gold nanoparticles.3b But
we found that chitosan is more than a protecting agent and
that gold salt can be reduced to zerovalent gold nanoparticles
by chitosan itself without any additional reducing agent. Gold
nanoparticles with different size distribution could be
* Corresponding author. Fax: +86-431-5689711. E-mail: xryang@
ciac.jl.cn.
10.1021/bm0497116 CCC: $27.50
Published on Web 09/03/2004
reducing/stabilizing agent. Chitosan, with excellent biode-
gradable and biocompatible characteristics, is a naturally
occurring polysaccharide. Using chitosan for the reduction
and stabilization of formed gold nanoparticles will not
introduce any environmental toxicity or biological hazards.
With the increasing interest in the minimization or total
elimination of waste and the implementation of sustainable
processes through the adoption of 12 fundamental principles
of green chemistry,7 the development of biological and
biomimetic approaches for the growth of advanced materials
is desirable. And this method for the preparation of gold
nanoparticles may be amenable to a cleaner large-scale
industrial production. Due to the unique polymeric cationic
character of chitosan and its gel- and film-forming properties,
chitosan has been extensively examined in the pharmaceutical
industry for its potential use in the development of controlled
release drug delivery systems.8 The polycationic nature of
chitosan results in polycondensation in the presence of
anionic molecules. Tripolyphosphate (TPP) is a typical
polyanion that can diffuse into chitosan droplets or films
freely to form ionically cross-linked chitosan beads or films.9
Many works have been done on the formation of chitosan
nanoparticles based on the ability of chitosan to undergo a
liquid gel transition due to the ionic interaction with TPP.10
Given that chitosan is a cationic polymer, our study was
based on inducing the gelation of chitosan by controlling its
interaction with the counterion TPP. In this sense, it is known
that the inter- and intramolecular linkages created between
TPP and the positively charged amino groups of chitosan
are responsible for the success of the gelation process, which
resulted in a suspension of chitosan nanoparticles in a certain
concentration of chitosan and TPP. More interestingly, this
gelation did not prevent the reduction of gold salt into
zerovalent gold nanoparticles by chitosan. And gold nano-
particles with bimodal size distribution could be obtained
© 2004 American Chemical Society
Chitosan-Stabilized Gold Nanoparticles Biomacromolecules, Vol. 5, No. 6, 2004 2341

when gold salts were exposed to the mixture of chitosan/

TPP. In addition to spherical gold nanoparticles, polygonal
gold crystals were also obtained.

Experimental Section

Materials. HAuCl4 was purchased from Aldrich and used

without further purification. Medium molecular weight
chitosan (poly-(1,4-β-D-glucopyranosamine), 400 000 g/mol)
with a degree of deacetylation of 100% was purchased from
Fluka, and lower molecular weight chitosan (poly-(D-
glucosamine), <5400 g/mol) with a degree of deacetylation
of 84.5% was bought from Aldrich. Tripolyphosphate
(Na5P3O10, TPP) was bought from Sigma, and all compounds
were used as received. Acetic acid (A. R.) was diluted to
1% aqueous solution before use. All aqueous solutions were
made with ultra-high-purity water purified with an ultrapure
water system Mill-Q Plus (Millipose Co.).
Preparation of Gold Nanoparticles Using Chitosan in
the Absence of TPP. All glassware used was cleaned in a
bath of freshly prepared aqua regia solution (HCl:HNO3 3:1)
and then rinsed thoroughly with H2O prior to use. Before
the preparation of gold nanoparticles, the stock solutions of
2.5% chitosan with medium molecular weight (CHI-medium,
Mw ∼ 400 000 g/mol, 100% deacetylated) and lower mo-
lecular weight (CHI-lower, <5400 g/mol, 84.5% deacety-
lated) were prepared by dissolving a certain amount of
chitosans in 1% acetic acid solution. Due to the poor
solubility of chitosan, the mixture was vortexed and kept
for about 1 week until a clear solution was obtained. When
used in the experiments, the stock solution was diluted to
the needed concentration.
An aqueous solution of HAuCl4 (1 mL, 1 mM) was mixed Figure 1. UV-vis absorption spectra of gold nanoparticles prepared
with a diluted solution of chitosan (3 mL, varied concentra- by different concentrations of medium molecular weight chitosan (a)
tion), and then the mixture was heated to 70 °C under and lower molecular weight chitosan (b).
magnetic stirring using a water bath until a red solution was
obtained. The reaction time is adjusted by the concentration 500 UV-vis-NIR spectrophotometer (Varian, Australia Pty
of chitosan, although a 2 h reaction time is enough. Ltd.).
Preparation of Gold Nanoparticles Using Chitosan in
the Presence of TPP. An aqueous solution of TPP (varied
volume, 0.1%) was added to 3 mL of a chitosan solution Results and Discussion
(0.05%) under magnetic stirring. Fifty minutes later, an
aqueous solution of HAuCl4 (1 mL, 1 mM) was added, and Gold Nanoparticles Prepared by Chitosan in the
heated to 70 °C using a water bath. After a reddish color Absence of TPP. We have reduced 1 mM solutions of
appeared, stirring continued for another 90 min before HAuCl4 by chitosan, and the UV-vis absorption spectra of
removing the heater; the resulting solution was cooled to the solutions are shown in Figure 1, which were collected
room temperature for characterization. after 2-h heating with a 70 °C water bath. Different
Transmission Electron Miscroscopy (TEM) and UV- concentrations of chitosan with medium molecular weight
Vis Characterization. Transmission electron microscopy (CHI-medium, Figure 1a) and with lower molecular weight
(TEM) was carried out with a JEOL-2000EX TEM operating (CHI-lower, Figure 1b) were used. All spectra exhibit an
at 160 kV. Specimens for inspection by TEM were prepared absorption band around 520 nm, which is a typical plasmon
by slowly evaporating one drop of prepared gold nano- resonance band for gold nanoparticles, suggesting the forma-
particles solutions at room temperature on a 400 mesh copper tion of gold nanoparticles.1b-f,2d,e,11 The plasmon absorption
grid, which was covered by a carbon-supported film. UV- of gold nanoparticles varies with the concentration of
vis absorbance spectrometric of gold nanoparticles was chitosan of both molecular weights. When the concentration
collected using a UV-2450 UV-visible spectrophotometer of CHI-medium is increased, the intensity of the absorption
(Shimadzu, Japan) with a slit width of 2.0 nm. The time- increases too and then decreases with a further increase of
dependent UV-vis spectra of gold nanoparticles were the concentration. But for CHI-lower, it is a little different;
recorded at 70 °C using a temperature controller on a Cary the intensity of the absorption band first decreases and then
2342 Biomacromolecules, Vol. 5, No. 6, 2004 Huang and Yang

increases with the growing concentration of chitosan. The

background absorption goes up with the increasing concen-
tration of chitosan, especially for the lower molecular weight
chitosan. But this difference does not affect the plasmon
resonance band of gold nanoparticles obtained. The UV-
vis spectra of different concentration of chitosan were
illustrated in the Supporting Information (see Figure 1a,b of
the Supporting Information). This result indicates that the
size of gold nanoparticles formed varies with the concentra-
tion of chitosan, which acts as a controller of nucleation as
well as a stabilizer.
The difference in UV-vis absorption suggested the
difference in shape or size distribution of gold nanoparticles
obtained, which is further confirmed by transmission electron
microscopy (TEM) observations. TEM images of gold
nanoparticles reduced/stabilized by different molecular weight
chitosan are illustrated in Figure 2. Parts A, a, B, and b of
Figure 2 are TEM images prepared by 0.05% and 0.25%
CHI-medium, while parts C, c, D, and d of Figure 2 are
TEM images of gold nanoparticles obtained by 0.05% and
0.25% CHI-lower. In general, the particles were spherical
in shape, and particle size and size distributions varied
slightly with the concentration and molecular weight of
chitosan. Gold nanoparticles prepared with relatively high
concentration of chitosan have a higher stability. When the
concentration of chitosan was increased from 0.05% to
0.25%, no obvious changes in particle size and size distribu-
tion could be observed for gold nanoparticles prepared by
CHI-medium. However, when a much lower concentration
of chitosan was used, such as 0.005% or 0.01%, gold
nanoparticles prepared were ready to aggregate and precipi-
tate from the solution during stirring. UV-vis absorption
spectra and TEM images of gold nanoparticles prepared with
0.01% chitosan are shown in Figure 3. Gold nanoparticles
prepared with 0.01% CHI-medium were large in size, and
in addition to spherical particles, polygonal gold nanocrystals
were also observed.
From Figure 2 (C,c;D,d), we can see when CHI-lower was
used in the preparation, increasing the concentration of
chitosan, the particle size distribution of gold nanoparticles
obtained was narrower than with a lower concentration of
chitosan. Upon further increasing the concentration of Figure 2. TEM images of gold nanoparticles prepared by 0.05%
chitosan, no obvious changes in particle size and size (A, a) and 0.25% (B, b) medium molecular weight chitosan and 0.05%
(C, c) and 0.25% (D, c) lower molecular weight chitosan.
distribution were observed. The TEM images of gold
nanoparticles prepared with 0.5% CHI-lower are included To get further insight into the formation of gold nanopar-
in the Supporting Information as Figure 2. These results ticles by chitosan, we also performed in situ UV-vis
illustrate the formation of gold nanoparticles inside the experiments at a constant temperature of 70 °C. Figure 4
nanoscopic polysaccharide templates. The electrostatic at- shows the time-dependent UV-vis spectra of mixtures
tractive forces between amino groups in chitosan and metal containing 1 mL of 1 mM HAuCl4 and 0.05% (A) and 0.25%
salt ions (here is AuCl4-) in solution provide an effective (B) medium molecular weight chitosan solution. The spectra
driving force in formation and stabilization of these metal were collected at a time interval of 5 min. With a concentra-
nanoparticles. Changes in particle size and size distribution tion of 0.05%, the induced time was quite short (about 5
of gold nanoparticles with the concentration of chitosan may min) and the absorbance increased very quickly to level off
be decided by the role chitosan plays, the controller of about 110 min. At a higher concentration of chitosan, the
nucleation or the stabilizer. When the concentration of induced time was longer (about 20 min) and the increase of
chitosan is low, up to 0.01%, few chitosan molecules work absorbance is slower; in such a case, the absorbance leveled
as stabilizer by adsorbing on the surface of gold nano- off in about 150 min, which means a longer reaction time.
particles, which resulted in the formation of large gold The shorter induced time and fast reduction of HAuCl4 by
nanoparticles, as shown in Figure 3. 0.05% chitosan may be due to the fast diffusion of AuCl4-
Chitosan-Stabilized Gold Nanoparticles
Figure 3. UV-vis absorption spectra and TEM images of gold
nanoparticles prepared by 0.01% medium molecular weight chitosan
collected at 40 min (a) and 90 min (b).
ions in a more dilute chitosan solution, which results in a
quick nucleation of gold nanoparticles. And with a lower
concentration of chitosan, chitosan molecules adsorbing on
the surface of gold nanoparticles are very few; thus, large
gold nanoparticles are formed. On the other hand, the slight
blue-shift in the maximum absorption in the UV-vis spectra
may be due to the decomposition and recombination of gold
nanoparticles in the process of reaction with the eventual
narrowing of the size distribution as the reaction reaches an
equilibrium (see Figure 3 of the Supporting Information).
This phenomenon is more obvious with a much lower
concentration of chitosan, as shown in Figure 3.
When 0.01% chitosan was used in the preparation of gold
nanoparticles, first the color changed from the yellow of
HAuCl4 to blue, and then it became red-purple at about 90
min, which means the reduction of HAuCl4 to gold nano-
particles. This color change was confirmed by UV-vis
absorption spectra and TEM images of gold nanoparticles
collected at different reaction time (see Figure 3). There are
two distinct absorption bands, one is within 500-600 nm,
and the other is at 600-900 nm. The absorption band within
500-600 nm is attributed to the transverse plasmon band
(TPB) of gold spheres, which arises from the collective
oscillations of the conduction band electrons. The blue-shift
in maximum absorption arose from the size change of the
spherical gold nanoparticles. The other one (600-900 nm)
is mainly induced by the extended plasmon band (EPB),
which can be observed in the strong interparticle interaction
among aggregates12 and the deviation from spherical geom-
etry13,14 of gold nanoparticles. TEM images (Figure 3a,b)
further confirmed this in the morphological aspect. In Figure
3a, the morphology of gold nanoparticles was anomalous
and large, but with long reaction time, gold nanoparticles
Biomacromolecules, Vol. 5, No. 6, 2004 2343
Figure 4. Time-dependent UV-vis absorption spectra of solutions
containing 1 mM HAuCl4 and 0.05% (A) and 0.25% (B) medium
molecular weight chitosan.
decomposed and recombined, and inerratic spherical or
polygonal gold particles were formed, as shown in Figure
3b.
Gold Nanoparticles Prepared by Chitosan in the
Presence of TPP. Many works have demonstrated that TPP
can ionically cross-link with chitosan to form a constant gel-
like opalescent suspension in a certain concentration of TPP
and chitosan, which is called chitosan nanoparticles. Oth-
erwise, a clear solution or precipitation could be obtained.
According to our test result, when the concentrations of
chitosan and TPP were in the range of 0.9-3 and 0.3-0.8
mg/mL, respectively, chitosan nanoparticles could be ob-
tained, which is consistent with the report in the literature.10c,15
When 0-1000 µL of 0.1% TPP was added to 3 mL of 0.05%
chitosan solution, two kinds of solution could be obtained,
one is a clear solution and the other is a suspension of
chitosan nanoparticles. The UV-vis spectra are included in
the Supporting Information as Figure 1c to present an idea
of the opacity of the solutions used. When a solution of
HAuCl4 was added to the resulting chitosan-TPP solution,
zerovalent gold nanoparticles could also be obtained by using
the same method as without TPP.
Figure 5 shows UV-vis spectra of gold nanoparticles
prepared by chitosan in the presence of different amounts
of TPP. The plasmon absorption of gold nanoparticles
2344 Biomacromolecules, Vol. 5, No. 6, 2004
Figure 5. UV-vis absorption spectra of gold nanoparticles prepared
by medium molecular weight chitosan in the presence of various
amount of 0.1% TPP.
prepared by chitosan without TPP took place at 522 nm. By
adding a different volume of 0.1% TPP solution, the plasmon
absorption shifts to longer wavelength with larger addition
volume. When the amount of TPP added was up to 750 µL
or more, the solution was an opalescent suspension, and
another absorbance around 600 nm was observed, which may
be due to the bimodal size distribution16 or deviation from
spherical geometry of gold nanoparticles. Figure 6 shows
the TEM images of gold nanoparticles prepared in the
presence of different amounts of TPP and the histogram of
particle size distribution. These images show a bimodal size
distribution of gold nanoparticles. In Figure 6a,d, it can be
seen that gold nanoparticles are isotropic (i.e., low aspect
ratio) in shape when prepared in the absence of TPP. After
the addition of TPP, small particles and large particles both
existed, and the size distribution was very broad. But in
addition to spherical gold nanoparticles, polygonal gold
Figure 6. TEM images and the histograms of particle size distribution of gold nanoparticles prepared in the presence of various amount of
0.1% TPP: (a, d) 0 µL, (b, e) 500 µL, and (c, f) 1000 µL.
Huang and Yang
nanocrystals, such as triangular or rectangular gold nanoc-
rystals, could also be obtained, so we cannot exclude that
the appearance of the absorption band around 600 nm is not
mirrored by the appearance of anisometric gold particles.14
Interestingly, when 500 µL of TPP was added, we observed
no suspension with the naked eye, but some very large
polygonal gold nanocrystals could be observed under trans-
mission electron microscopy. The TEM images and electron
diffraction patterns of these large gold nanocrystals are shown
in Figure 7. These large particles are regular polygon, and
from electron diffraction pattern analysis, the spot array,
diagnostic of a hexagonal structure, is from the {111}
orientation of the platelet lying flat on the substrate with the
top facet perpendicular to the electron beam. In this case,
the formation of larger polygonal gold nanoparticles may
be due to the preferential growth of the {111} facet of the
gold crystals formed. Similar gold nanocrystals were also
obtained by aspartate reduction of gold chloride recently.17
In this paper, we demonstrated that HAuCl4 can be reduced
into zerovalent gold nanoparticles by chitosan both in the
absence and in the presence of TPP. It is very clear that
chitosan plays a role as a reducing agent, but the exact
mechanism of the reduction is not clear. We know glucose
is a reducing sugar, and it has been used as a reducing agent
in the preparation of metal nanoparticles.5 In chemical
structure, chitosan is a polysaccharide, which can hydrolyze
in an aqueous acid to give D-glucosamine,18 a derivative of
glucose. So we suggested the same mechanism of reduction
of metal salts as for glucose. On the other hand, the -CH2-
OH groups in molecular chitosan may also act as a reducing
group in the formation of gold nanoparticles. For the
formation of polygonal gold particles, TEM images proved
that these polygonal particles cannot be the aggregates of
small gold particles. We did not observe the formation of
chitosan nanoparticles in our experiments under TEM, and
Chitosan-Stabilized Gold Nanoparticles Biomacromolecules, Vol. 5, No. 6, 2004 2345

and National Key Basic Research Development Project

“Research on Human Major Disease Proteomics” (No.
2001CB5102).

Supporting Information Available. UV-vis spectra of

different concentration of chitosan (Figure 1), TEM images
of gold nanoparticles prepared with 0.5% CHI-lower (Figure
2), and UV-vis absorption spectra and TEM images of gold
nanoparticles prepared by 0.05% medium molecular weight
chitosan (Figure 3). This material is available free of charge
via the Internet at http://pubs.acs.org.

References and Notes

Figure 7. TEM images and electron diffraction patterns of gold
nanoparticles prepared with chitosan in the presence of 500 µL of
0.1% TPP.
the interaction between chitosan and AuCl4- may also effect
the interaction of chitosan and TPP. We proposed the
formation of polygonal gold particles by adding TPP into
the system, which is comparable to that formed by using
0.01% chitosan. When adding more TPP into the chitosan
solution, more chitosan molecules bind to TPP to form a
hydrogel. Fewer chitosan molecules are absorbing on the
surface of preformed gold nanoparticles, and in the process
of decomposition and recombination, gold nanocrystal are
ready to form polygonal particles due to the haphazard crystal
growth.
Conclusion
This study shows that chitosan is a very effective reducing/
stabilizing agent for the preparation of gold nanoparticles.
In general, gold nanopartles prepared have a high stability,
without obvious aggregation within two months. Gold
nanoparticles with different size distribution could be
obtained by using a different concentration and molecular
weight of chitosan. Chitosan has a special gelling quality
upon contacting with the counterion TPP. In a certain
concentration of chitosan and TPP, a suspension of chitosan
nanoparticles could be formed. When gold salt was added
to this suspension of chitosan nanoparticles, zerovalent gold
nanoparticles could also be obtained, but with different shape
and size distribution. We also proposed some explanations
for the reduction mechanism of gold salts by chitosan and
the formation of polygonal gold particles. Our proposed
method for the preparation of gold nanoparticles was
considered to be a green approach because of the use of a
naturally occurring polysaccharide, chitosan, as both reducing
and stabilizing agent. Moreover, the abounding existence of
raw materials makes it amenable to a cleaner large-scale
industrial production.
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