STUDY ON SELECTED SYNTHESES OF GOLD NANOPARTICLES khóa luận tốt nghiệp tiếng anh

Phan Thi Thanh Binh K52 Advanced Program Chemistry
VIETNAM NATIONAL UNIVERSITY, HANOI
HANOI UNIVERSITY OF SCIENCE
FACULTY OF CHEMISTRY
Phan Thi Thanh Binh
STUDY ON SELECTED SYNTHESES OF GOLD
NANOPARTICLES
Submitted in partial fulfillment of the requirements for the degree of
Bachelor of Science in Chemistry
(Advanced Program)
Hanoi - 2012
Phan Thi Thanh Binh K52 Advanced Program Chemistry
VIETNAM NATIONAL UNIVERSITY, HANOI
HANOI UNIVERSITY OF SCIENCE
FACULTY OF CHEMISTRY
Phan Thi Thanh Binh
STUDY ON SELECTED SYNTHESES OF GOLD
NANOPARTICLES
Submitted in partial fulfillment of the requirements for the degree of
Bachelor of Science in Chemistry
(Advanced Program)
Hanoi - 2012
Phan Thi Thanh Binh K52 Advanced Program Chemistry
ACKNOWLEDGEMENT
I would like to express my gratitude Assoc. Prof. Dr. Tran Thi Nhu Mai for her
supervisor and guidance throughout all of my researches.
A very special thanks goes out to Professor Catherine J. Murphy and her group's
members, who gave truly help the progression and smoothness of the internship
program in University of Illinois at Urbana Champaign.
I am also thankful all of other members of Laboratory of Organic Catalyst for
their helps during my working time.

Phan Thi Thanh Binh K52 Advanced Program Chemistry
ABSTRACT
Nanoparticles, already widely applied in diverse fields from catalysis to bio-
imaging, have undergone tremendous development in the past two decades, where size
control of spherical nanocrystals of semiconductors, metals and insulators has been
achieved for almost any material. The published results has proven that gold nano-
materials possess strong and unique characteristics being hopeful to apply on a variety
of fields, especially in Chemistry for catalyst purposes or biochemical purposes.
In this research, the seeded - growth and hydrolysis Stober's method was applied
to synthesize and overcoat gold nanorods aiming to biomedical purposes. Moreover,
the hydrothermal method was used to nail gold nanoparticles on the Si template
orienting to the green catalyst. The results showed by physical methods such as Zeta-
potential, transmission electron microscope (TEM) or UV-Vis. EDX and N
2
adsorption/desorption measurements have confirmed the effective of these methods.
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Table of Contents
Table of Contents 5
INTRODUCTION 8
CHAPTER 1: OVERVIEW OF GOLD NANOPARTICLES 9
1.1 BACKGROUND OF METAL NANOPARTICLES 9
1.2 OVERVIEW OF GOLD NANOPARTICLES 10
1.2.1 Properties and Applications 11
1.2.2 Synthesis and Functionalization 20
1.3 GOLD NANORODS 29
1.3.1 Optical properties 29
1.3.2 Synthesis methods 31
1.3.3 Silica coating 34
1.3.4 Applications 35
CHAPTER 2: EXPERIMENT 36

2.1 Seeded - growth method to synthesize gold nanorods 36
2.2 Hydrolysis Stober method to silica - coating gold nanorods 36
2.3 Hydrothermal method to synthesize gold nanoparticles template 37
2.4 Characterization Methods 38
CHAPTER 3: RESULTS AND DISCUSSIONS 44
3.1 PURPOSES 44
3.2 SYTHESIS AND CHARACTERIZATION OF GOLD NANORODS 45
3.2.1 The effects of AgNO3 volume on obtained gold nanorods 46
3.2.2 Effects of PEG - coating and silica - coating on gold nanoparticles 48
3.3 SYNTHESIS AND CHARACTERIZATION OF AU/SI (Au/Si_01) 53
3.2.1 N2 adsorption-desorption measurements 55
3.2.2 TEM, EDX and AAS methods 56
3.4 PROSPECTIVE APPLICATIONS 58
3.4.1 Gold nanorods 58
3.4.2 Au/Si material 59
CONCLUSION 61
REFERENCE 62
Phan Thi Thanh Binh K52 Advanced Program Chemistry
LIST OF FIGURES
Figure 1: Exponential growth in the number of publication on gold nanotechnology and nano-
medicine over the two past decades.[6] 11
Figure 2: Conversion of glucose to gluconic acid in alkaline aqueous solution 12
Figure 3: Approaches of loading/unloading therapeutics 17
Figure 4: Loading drugs into the interior of gold nanoparticles 18
Figure 5: Scheme of sensing layer preparation using both peptide and antibody 19
Figure 6: Gold nanodendrites 20
Figure 7: Gold Nanorods [21] 21
Figure 8:Sharpened nanorods [22] 21
Figure 9: Nanocages/nanoframes 22
Figure 10: Nanoshells [24] 22

Figure 11: Hallow gold nanosphere 23
Figure 12: (a) tetrahedra/octahedra/cubes/icosahedra, (b) rhombic dodecahedra, (c) octahedra 23
Figure 13: Nanocubes 23
Figure 14: Complex nanostructures 24
Figure 15: (a) hydrophobic entrapment, (b) electronstatic adsorption[6] 27
Figure 16: Silance conjugation of gold nanoparticle 28
Figure 17: Electron micrograph of a silica sphere sample 28
Figure 18: UV- Vis spectra of gold nanorods with aspect ratios: (A) 1.42 ± 0.32, (B) 1.82 ± 0.49, (C) 2.31
± 0.55, (D) 2.65 ± 0.43, and (E) 2.80 ± 0.37 30
Figure 19: Illustration of changes of gold nanorod colors due to aspect ratio 30
Figure 20: Scheme of template approach of gold nanorods 31
Figure 21: a, Scheme of electrochemical approach of gold nanorods b, TEM of gold nanorods at other
aspect ratios obtained by elec. method 32
Figure 22: Illustration for gold nanorods growth in the absence of silver ion 33
Figure 23: Proposed formation of gold nanoparticles 33
Figure 24: Illustration: gold nanorods growth in the presence of silver ion 34
Figure 25: Scheme of seeded - growth method procedure 45
Figure 26: UV - VIS of rainbow solutions 46
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Figure 27: The formation of gold nanorods in the presence of Ag 47
Figure 28: TEM image of 10Ag sample 47
Figure 29: Scheme of PEG, silica - modification procedure 48
Figure 30: TEM of mPEG - SH coated gold nanorods PEG-6Ag 50
Figure 31: UV - VIS of PEG-6Ag and Sil-6Ag 51
Figure 32: TEM of Silica - coated nanorods Si-6Ag 52
Figure 33: Scheme of synthesis template procedure 53
Figure 34: Scheme of preparing Au/Si procedure 54
Figure 35: BET of Au/Si_01 55
Figure 36: Pore distribution of Au/Si_01 56
Figure 37: TEM image of Au/Si_01 57

Figure 38: EDX spectrum of Au/Si 58
Figure 39: Typical properties and applications of gold nanorods [43] 59
Figure 40: Products containing calcium gluconate 60
LIST OF TABLES
Table 1: Gold nanoparticles in photothermal therapy applications 15
Table 2: Summary of synthetic approaches to obtain various gold nanostructures 24
Table 3: Outline of relation between stability and zeta-potential 40
Table 4: Data of rainbow gold nanorods 46
Table 5: BET - data of Au/Si_01 55
Phan Thi Thanh Binh K52 Advanced Program Chemistry
INTRODUCTION
Normally, we also know that pure gold is a transition metal in the group 11 of
periodical table. It has a very high melting point and shows the nature as one of the
least reactive metals. However, it exhibits a beautiful appearance, amazing malleability
and ductility, of course, good conductivity. That means why gold have been more
widely used to craft expensive ornaments or gild electronic accessories than apply on
chemical field.
However, in the recent researches, the scientists have discovered that gold on
nanoscale represents a huge number of predominant effects that are full of promises to
play the role of aurotherapy, photothermal argents, and especially catalysis, optical
materials and biomedicine such as drug therapy or biosensor.
In fact, Murphy et al.[1] and Nikoobakht and El-Sayed[2] have been successful
to demonstrate a colloid method to synthesize mono - disperse nanorods at high yield
based on seeded growth method. After that, to increase the biological compatibility,
nanorods will be coated and functionalized by other materials, generally for instance, a
variety of silicates or polymers, which have the functional groups to be similar to acid
amines, enzymes such as thiolate, amines, carboxylate etc. In the first part of this
research, I have already prepared nanorods based on seeded - growth theory in the
Phan Thi Thanh Binh K52 Advanced Program Chemistry
presence of silver and cationic surfactant CTAB and . Then the Stober method was

used to overcoat the nanorods by silica (i.e, TEOS)
On the other hands, although gold is the most inert of all metallic elements, but
many studies have proven that gold nanoparticles also have appropriate properties as
heterogeneous catalysts. The right explanation has been debated, however, one
possibility explaining this phenomenon might be because of the availability of surface
gold atoms with low coordination number and the associated electrons density for
whatever reactions is being catalyzed [3]. But it cannot deny that nanogold has played
an important role in the Chemistry as the green catalyst for many reactions, especially
for Organic chemistry. So we have built a process to nail the gold - nanoparticles on
the template reigned P123 and TEOS by hydrothermal method orienting to catalyze for
reaction of producing calcium gluconate from natural D - Glucose.
CHAPTER 1: OVERVIEW OF GOLD NANOPARTICLES
1.1 BACKGROUND OF METAL NANOPARTICLES
Just as in bulk metals, electrons in the conduction band of nanoscale metals are
free to oscillate upon excitation with incident radiation, referred to as the localized
surface plasmon resonance (LSPR). However, on the nanoscale, the oscillation
distance is restricted by the nanoparticle size. For gold nanoparticles, LSPR
corresponds to photon energies in the visible wavelength regime, giving rise to
significant interest in their optical properties. These optical characteristics include
strong plasmon absorption, resonant Rayleigh scattering, and localized electromagnetic
fields at the nanoparticle surface.
Actually, plasmon absorption in metal nanoparticles is highly dependent on
nanoparticle shape, size, and dielectric constant of the surrounding medium [4]. One
area of catalysis that is developing at a rapid pace is nanocatalysis. Striking novel
catalytic properties including greatly enhanced reactivities and selectivities have been
reported for nanoparticle (NP) catalysts as compared to their bulk counterparts. In
order to harness the power of these nanocatalysts, a detailed understanding of the
origin of their enhanced performance is needed [5]. Many experimental studies on
nanocatalysts have focused on correlating catalytic activity with particle size. While
Phan Thi Thanh Binh K52 Advanced Program Chemistry

particle size is an important consideration, many other factors such as geometry,
composition, oxidation state, and chemical/physical environment can play a role in
determining NP reactivity. However, the exact relationship between these parameters
and NP catalytic performance may be system dependent, and is yet to be laid out for
many nanoscale catalysts. Clearly, a systematic understanding of the factors that
control catalyst reactivity and selectivity is essential if trial and error methods are to be
avoided.
1.2 OVERVIEW OF GOLD NANOPARTICLES
The first scientific report describing the production of colloidal gold
nanoparticles was published in 1857 when Michael Faraday found that the ‘‘fine
particles’’ formed from the aqueous reduction of gold chloride by phosphorus could be
stabilized by the addition of carbon disulfide, resulting in a "beautiful ruby fluid".
Actually, the Human has a huge step up to approach the gold nanoparticles. Nowadays,
most colloidal synthetic methods for obtaining gold nano particles follow a similar
strategy, whereby solvated gold salt is reduced in the presence of surface capping
ligands which prevent aggregation of the particles by electrostatic and/or physical
repulsion.
Gold nanoparticles have been used
in biomedical applications since their first
colloidal syntheses more than three
centuries ago. Actually, over the past two
decades, their beautiful colors and unique
electronic properties have also attracted
serious attention due to their historical
applications in art, medicine and current
applications in enhanced optoelectronics
and photovoltaics. In spite of their modest
alchemical beginnings, gold nano-particles
possess physical properties that are
significantly different from both small

molecules and bulk materials, as well
as from other nano-scale particles.
-Moreover, their unique combination
of properties is just beginning to be
fully realized in range of medical
diagnostic and therapeutic applications
[6].
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Figure 1: Exponential growth in the
number of publication on gold
nanotechnology and nano-medicine
over the two past decades.[6]
To meet the variety of demands, many different methods have been discovered
and practised successfully to make a variety of gold nanoparticles forms such as
nanorods, nanocages, pyramid etc. Particle size is also adjusted by varying the gold
ion: reducing agent or gold ion : stabilizer ratio, with larger (and typically less
monodisperse) sizes obtained from larger ratios.
1.2.1 Properties and Applications
In his own paper on News & Views, using only one short sentence "Nanocystals
- Tiny seeds make a big difference"[7],

Uri Banin of The Hewber University of
Jelusalem has covered all valuable meanings of nanoparticles in general and gold
nanoparticles in specific in the Human living. Up to now, depending on the specific
properties, the applications of gold nanoparticles can divide in four main parts:
catalysis, optical applications, biomedicine and sensors.
Catalysis
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Nanoparticulate Au catalysts are unique in their activity under mild conditions,
even at ambient temperature or less. When Au nanoparticles less than ~ 5 nm in size

are supported on base metal oxides or carbon, very active catalysts are produced. One
of the potential advantages that Au catalysts offer compared with other precious metal
catalysts is lower cost and greater price stability, Au being substantially cheaper (on a
weight for weight basis) and considerably more plentiful than Pt. A huge number of
publications have exhibited the various application of gold nanoparticles as the role of
catalyst such as: pollution and emission control, chemical processing of bulk and
specialty chemicals, clean hydrogen production for the emerging hydrogen economy
including fuel cells, sensors for detecting pollutants [8].
Chemical Processes
Gluconic acid is an important food and beverage additive, and is also used as a
cleansing agent. The German group of researchers has suggested that the oxidation of
glucose to gluconic acid can be maintained at high activity and selectivity using a
stirred tank reactor for up to 110 days with a nanoparticulate Au on alumina catalyst
prepared by deposition precipitation with urea and incipient wetness methods (Fig. 2)
[9].
Figure 2: Conversion of glucose to gluconic acid in alkaline aqueous solution
Another differential of glucose - methyl gluconate, which plays an important
role as a solvent for semiconductor manufacturing processes, as a building block for
cosmetics, and as a cleaner for boilers and metals, has been also demonstrated a
process using Au catalyst with a capacity tons of month. So the methyl gluconate can
be synthesized directly by one - step production:
2 2 2 2 2
2HOCH CH OH MeOH O OHCH COOMe H O
+ + → +
Phan Thi Thanh Binh K52 Advanced Program Chemistry
The first application of Au/Pt catalyst in the vinyl acetate monomers (VAM)
manufacturing has been established. In the industrial scale, VAM is produced from
ethene, acetic acid, and oxygen using Au–Pd catalysts:
2 2 3 2 2 2 2 3 2
1

.
2
CH CH CH CO H O CH CH O CCH H O= + + → = +
In this case, the catalyst is durable and typically lasts for between one and two years.
Additionally, the presence of Au leads to a significant increase in space-time yield
compared with use of Pd alone, and the presence of Au clearly has commercial
importance.
Besides, there are a variety of applications in this fields, but these are the most
typical examples of using gold nanoparticles as catalysts for chemical processes
Pollution control
Au catalysts are highly active for the oxidation of many components in ambient
air at low temperatures, particularly CO and nitrogen-containing malodorous
compounds, such as trimethylamine. This ability offers scope for applications in air
quality improvement and control of odors, be they in buildings, transport, or other
related applications such as gas masks.
Fuel cells and hydrogen production
For use in a fuel cell, the remaining CO in this reversible reaction must be
removed to prevent it poisoning the Pt catalyst in the fuel cell. Au catalysts have been
found to be effective for this at room temperatureNanoparticulate Au on oxide can be
used to catalyze the water gas shift to produce hydrogen from CO and steam:
2 2 2
CO H O H CO
+ → +
Sensors
The requirement of air-quality monitoring demands the development of sensors
that are selective for the detection of individual pollutant gases. It is particularly
convenient that Au catalysts can operate at ambient temperatures. Gas sensors based on
nanoparticulate Au have therefore been developed for detecting a number of gases,
including CO and NO
x

. Au is also particularly promising for color-change sensors used
for monitoring components of body liquids.
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Optical properties - Chemical sensors and Imaging
Strong plasmon absorption and sensitivity to local environment have made
metal nanoparticles attractive candidates as colorimetric sensors for analytes including
DNA, metal ions, and antibodies [10]. These visible color changes are due to metal
nanoparticle aggregation, which in turn affects the plasmon coupling and induced
dipoles. Taking the example of use of gold nanoparticles as selective sensors for Li
+
[11], this solution-based sensor utilizes nanoparticles functionalized with a ligand that
binds to gold via a thiol at its back end, and a phenanthroline derivative at the front end
to selectively bind to Li
+
as a bidentate ligand.
Resonant Rayleigh scattering from metallic nanoparticles is a unique
characteristic of nanoscale metals. Due to the fact of the sensitivity of these plasmon
resonant particles (PRPs) to local chemical environment, refractive index, and
nanoparticle size and shape, resonant Rayleigh scattering from gold nanoparticles,
made by colloidal or lithographic techniques, has been utilizing for biological and
chemical analyses [12]. Moreover, the applications have been straighten in the elastic
light scattering from metallic nanoparticles that is measured to infer nanoparticle
position, local environment, or (in the case of nanorods) relative orientation.
Inelastic visible light scattering from metal nanoparticles is also a useful means
to gain chemical information about the nanoparticle’s environment. Surface-enhanced
Raman scattering (SERS) is a powerful analytical tool for determining chemical
information for molecules on metallic substrates on the 10 - 200 nm size scale. Raman
vibrations of molecules are in general very weak; but in the presence of metals (copper,
silver, gold) with nanoscale roughness, the molecular Raman vibrations excited by
visible light are enhanced by orders of magnitude.

In addition to SERS, surface enhanced fluorescence has also been reported for
molecules near the surfaces of metallic nanoparticles. While molecular fluorescence is
quenched within ~5 nm of the metal nanoparticle surface, at distances of ~10 nm or
greater, fluorescence is enhanced up to 100 - fold by the localized electric field and
increased intrinsic decay of the fluorphore [13].
Golden ages of biomedicine
Gold nanoparticles as intrinsic drug agents
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Gold nanoparticles of very small diameters (less than 2 nm) are able to penetrate
cells and cellular compartments (such as the nucleus) and can be extremely toxic [14].
Interestingly, larger sizes of gold nanoparticles with the same surface capping agent,
were found to be non-toxic under the same dosing conditions. Recently, it was found
that gold nano-particles (5 nm in diameter) exhibit anti-angiogenic properties (inhibit
the tumorigentic growth of new blood vessels) in both in vitro and in vivo studies.
Because of their comparable size relative to biomolecules and proteins, gold
nanoparticles can also interact with and modify physiological processes when
specifically localized within cells and tissues. They have explored similar strategies
whereby gold nanoparticles were found to selectively exert anti-proliferative and
radiosensitization effects.
Gold nanoparticles in photothermal therapy
Photothermal therapy is a central application of gold nano-particles in medicine.
The ability of gold nano-particles to absorb light and convert it to heat is a fascinating
property and has been employed to destroy cancer cells, bacteria, and viruses. Thus,
laser-exposed gold nanoparticles could act as therapeutic agents by themselves and
without the need for co-conjugated drugs.
Gold nanoparticles absorb light with high efficiency (extinction coefficient B10)
in the near-infrared (NIR) region of the electromagnetic spectrum, where attenuation
by biological fluids and tissues is minimal. Gold nanoparticles have the advantage of
higher absorption cross section, higher solubility, efficient absorption at longer
wavelengths, and facile conjugation with targeting molecules and drugs. These

properties make gold nanoparticles promising candidates for photothermal therapy of
cancer and various pathogenic diseases. The common use of gold nanoparticles in
photothermal therapy are abundant in the literature is sum up in Table 1.
Table 1: Gold nanoparticles in photothermal therapy applications
Nanoform Particle size (nm) Available region Applications
Gold - silica
nanoshells
110 - 150 Vis - NIR ablating various cancerous
cell lines in vitro and treating
of cancer in animal models in
vivo
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Nanorods 33.7 ± 3.5 x
9.1±1.4,
50 x 12, 13x 47 etc.
plasmonic
phototherapeutis
ablate tumors in mouse
models of colon cancer and
squamous cell carcinoma.
Nanocages 48.0 ± 3.5 NIR-absorbing Photothermal therapeutic
agents was demonstrated both
in vitro and in vivo.
Hollow gold
nanoshells
415 ± 2.3 NIR To be effective photo-thermal
therapeutics in both in vitro
and in vivo models.
Gold - gold sulfide
nanoparticles

45 NIR targeting and ablation of
melanoma tumors in vivo.
Gold nanoparticles as drug delivery vehicles
Nanoparticles have been used in exploratory drug delivery applications due to
the following 5 main reasons: (i) the high surface area of nanoparticles provides sites
for drug loading and enhances solubility and stability of loaded drugs, (ii) the ability to
functionalize nanoparticles with targeting ligands to enhance therapeutic potency and
decrease side effects, (iii) the advantage of multivalent interactions with cell surface
receptors or other biomolecules, (iv) enhanced pharmacokinetics and tumor tissue
accumulations compared to free drugs, and (v) biological selectivity which allows
nanoscale drugs to preferentially accumulate at tumor sites due to their ‘‘leaky’’ blood
vessels - the so - called enhanced permeability and retention (EPR) effect. Figure 3
focuses and expounds upon the use of gold nanoparticles of different shape/size in drug
delivery applications, each categorized by the previous methods in which their active
agent is loaded and/or released.
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Figure 3: Approaches of loading/unloading therapeutics
into/from gold nanoparticles
The illustration describes the partitioning and diffusion-driven release of hydrophobic
drug molecules in (a) a surfactant bilayer or (b) an amphiphilic corona layer. The
driving force for the observed release is re-partitioning of the drug from the polymer
monolayer on the gold nano-particles to hydrophobic domains in the cellular
membrane [15]. In other case drugs was anchored directly to the surfaces of gold
nanoparticles through Au–S or Au–N bonds (c) (capping agent in blue is hydrophilic
polymer,e.g. PEG, to enhance the overall solubility of the system). Release is triggered
by the photothermal effect, thiol exchange (e.g. glutathione exchange), or simple
diffusion to the cell membranes (in the case of Au–N). Additionally, (d–e) is using Au–
S bonding for double-stranded DNA-loaded gold nanoparticles. The release of double
(d) or single (e) stranded DNA is controlled by an applied laser. Using another way,
Therapeutic agents are coupled/complexed to terminal functional groups of the capping

agent via a cleavable linker (f). In this case, the gold surface is already passivated with
various functional groups and the drug attachment proceeds to the outermost layer on
top of the particles. Release can be triggered by hydrolysis, light, heat, and/or pH
changes. But in the case of (g), charged biomolecules ( e.g. DNA or siRNA) can be
easily attached to the surfaces of complementary charged gold nanoparticles by
electrostatic-conjugation or the related layer-by-layer (LbL) coating. Release of
payload can be triggered by the use of charge-reversal polyelectrolytes combined with
pH change. Finally, drug molecules are incorporated into the matrix of a thermo-
sensitive, crosslinked polymer (h). Then, release can be triggered by the photothermal
heating by gold nanoparticles also incorporated into the matrix.
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Furthermore, under the appropriate excitement, the loading inside the
nanoparticles could be happened by some ways.
Figure 4: Loading drugs into the interior of gold nanoparticles
In the detail:
(a) Gold nanocages (hollow gold cubes with porous walls) are functionalized
with a thermosensitive polymer brush layer at their exterior surface to cage drug
molecules in their interior. Laser irradiation induces local heat flux and thus, collapse
of the thermo-sensitive polymer to release the caged drug molecules.
(b) Gold nanocages with the drugs dispersed into a thermosensitive material in
the interior of the nanoparticles. Laser irradiation results in phase-change (melting) of
the thermosensitive ‘‘filler’’ and thus enhances drug release.
(c) A gold nanoshell covers a liposome carrying drugs in its interior. Gold
nanoshells absorb light and convert it to heat and these events result in disintegration
and clearance of the carrier, as well as release of its encapsulated drugs.
Optional applications
Besides the great potential for gold nanoparticles as drug delivery carriers, they
have also been used to stabilize and enhance the efficiency of other drug delivery
carriers such as liposomes and microcapsules. Moreover, gold nanoparticles were
incorporated in various types of materials to fabricate gold-containing devices for drug

delivery such as thermo-sensitive microcapsules, films, and hydrogels to use as a
component in composite materials for controlled drug delivery applications. The gold
particles were also aiming to target to diseased sites as well.
Phan Thi Thanh Binh K52 Advanced Program Chemistry
In the conclusion, with their exceptional properties, gold nanoparticles have
been played one of the most important roles in improving biomedicine. In the future,
they are also full of promising to apply in developing and optimizing biological
chemistry.
Applications of gold nanoparticles in Vietnam
In fact, the study of gold nanoparticles has not been truly developed in Vietnam
due to a lot of difficulties in required facilities and expenditure. However, recently,
Institute of Chemistry - Vietnam Academy of Science and Technology has been
successful to make electrochemical sensors based on gold nanopartcles. In the first
publication in 2009, they represented electrochemical method - square wave
voltammetric detection using gold biosensors for selective recognition of a protein
marker. The idea was that a short chain peptide would be utilized for the selective
electrochemical detection of the protein biomarker, protective antigen (PA), for the
diagnosis of Anthrax [16].
Figure 5: Scheme of sensing layer preparation using both peptide and antibody
Actually, the major motivation of using a peptide instead of an antibody for the
development of a biosensor is that there are advantages associated with the smaller
size, better biological stability and easy synthesizability of a peptide. In the
Phan Thi Thanh Binh K52 Advanced Program Chemistry
experiment, PA-selective peptide was synthesized and conjugated on a binding layer
previously immobilized onto gold electrode.
After that, in 2011, Huan at al. continued to published a paper related to gold
nanoparticles. But this time, he used 3D gold nanodendrite applying on an
electrochemical sensing for detection of As (III) in ultra low concentration range. The
results showed that the network porous structure of three - dimentional Au
nanodendrite could be greatly promising for high sensitive and selective detection of

diverse biomolecules when a target - specific sensing layer is formed in the surface of
structure [17].
Figure 6: Gold nanodendrites
In addition, the Au microelectrode sensor has been developed for detection of Hg (II)
in a low concentration as well. In short speaking, a simple and reproductile carbon
microelectrode array (CMA), designed to eliminate diffusive interference among the
microelectrodes, has been fabricated and used as a frame to build a gold nicroelectrode
array (GMA) sensor [18].
1.2.2 Synthesis and Functionalization
A variety of synthetic methods and gold nanoparticles forms
In historical sequence, interest in the shape-controlled synthesis of gold
nanostructures began booming in the early 1990's when Masuda et al. and Martin [19]
developed techniques to prepare gold nanorods by electrochemical reduction into
nanoporous aluminium oxide membranes. However, in the beginning, the obtained
nanorods had mono - disperse structures relatively, but because of the low yield and
large diameter (>100nm), the optical response is difficult to discern and largely
Phan Thi Thanh Binh K52 Advanced Program Chemistry
dominated by multipolar plasmon resonance modes [20]. This negative effects had
been improved by Wang and coworker later by electrochemical oxidation of a gold
plate electrode in the presence of cationic, quaternary ammonium surfactants (CTAB
or TOAB). The resulting particles synthesized by this method has only ~ 10nm in
diameter. It also existed many disadvantages needed to upgrade, though.
In general based on previous
achievements and in particularly seeded growth
method, Murphy et al. and Nikoobakht and El-
Sayed later demonstrated a colloidal growth
method to produce mono - disperse gold
nanorods in high yield (Fig. 7). In this method,
small (~1.5 nm diameter) single-crystal seed
particles, produced from the reduction of

chloroauric acid by borohydride in the presence
of CTAB, are aliquoted into Au(I) growth
solution prepared from the mild reduction of
Figure 7: Gold Nanorods

[21]
chloroauric acid by ascorbate and the addition of AgNO
3
and CTAB. As the result,
gold nanorods ca. 10–20 nm in diameter and up to 300 nm in length can be obtained in
relatively high yield. Furthermore, nanorod aspect ratio can be controlled by the
seed/gold salt ratio or by the relative concentration of additive impurity ions.
Figure 8:Sharpened
nanorods [22]
Liz-Marzan and coworkers also showed that
spherically-capped colloidal gold nanorods could be
reshaped to form single-crystal octahedra, using
poly(vinylpyrrolidone) (PVP) functionalized gold
nanorods as seeds for the ultrasound-induced reduction
of chloroauric acid by N, N-dimethylformamide (DMF)
in the presence of PVP [22]. The authors showed
that by increasing the ratio of gold salt to nanorod seeds, the subsequent morphology
varies from sharpened (octagonal) rods to tetragons to octahedra (Fig.8).
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Gold nanocages and nanoframes which
possess desirable optical properties and potentially
cargo-holding hollow structures recently developed by
Xia and coworkers (Fig. 9) . In this case, gold
nanocages/frames are produced by reacting Au(III)
with silver nanocubes produced from the polyol

reduction of silver nitrate, based on a phenomenon
known as galvanic replacement, whereby more noble
metal ions (e.g. Au, Pt) spontaneously oxidize the
surface atoms of a less noble metal (e.g. Ag, Cu) with
concomitant reduction of the more noble metal [23].
Figure 9:
Nanocages/nanoframes
Figure 10: Nanoshells [24]
Silica-gold coreshell nanoparticles, or
gold nanoshells (Fig. 10), have recently attracted
much attention, for example, Aden and Kerber
(1951) or Halas and his coworkers (1998), due to
their interesting optical properties and numerous
biomedical applications. In a typical synthesis,
silica nanoparticle cores are synthesized by the
base-catalyzed condensation of orthosilicate (i.e. Stober hydrolysis) and functionalized
with an amine - terminal silane. Small, anionic gold nanoparticles synthesized from the
aqueous reduction of chloroauric acid by tetrakis (hydroxymethyl) phosphonium
chloride (THPC) are electrostatically adsorbed onto the surfaces of the silica cores and
added to a solution of mildly reduced chloroauric acid. When formaldehyde is added to
the solution, the adsorbed gold particles serve as nucleation sites for the further
reduction of gold around the silicacore, subsequently forming a conformal nanoshell.
Caruso and coworkers obtained hollow gold nanospheres by calcination or
dissolution of polystyrene–gold core–shell nanoparticles (Fig.11). In this case,
polystyrene nanospheres were bounded by polyelectrolyte multilayer films and 4 -
(dimethylamino) pyridine (DMAP) stabilized
gold nanospheres (approx. 6 nm diameter) were
electrostatically adsorbed to the
polyelectrolyte surface. After that,
Phan Thi Thanh Binh K52 Advanced Program Chemistry

Liang et al. showed that similar structures could
be obtained by galvanic replacement with
citrate- stabilized cobalt nanospheres
synthesized from the reduction of CoCl
2
by
borohydride under anaerobic conditions [25].

Figure 11: Hallow gold
nanosphere
Other reports showed that more geometrically complex gold nanostructures
(100–300 nm in size) could be produced by a modified polyol process ( Fig. 12a)[26].
Figure 12: (a) tetrahedra/octahedra/cubes/icosahedra, (b) rhombic dodecahedra,
(c) octahedra
Murphy and Sau later built the high yield synthesis of complex gold nanostructures
via seed-mediated growth methods [31] in which by varying the concentrations of
Au(III), ascorbic acid, and presence of silver nitrate in the growth solution, as well as
the quantity of added seeds, rectangular, hexagonal, cubic, triangular, and star-like
nanoparticles were obtained. Moreover, other methods also led to obtained a variety of
forms of gold nanoparticles, for instant, rhombic dodecahedral morphology (Fig. 12b)
and octahedral geometries (Fig. 12c).
Figure 13: Nanocubes
Recently, a seeded growth technique analogous
to that used to produce nanorod have been applied by
Mirkin and coworkers to develop a method to
synthesize monodisperse gold nanocubes (Fig. 13), but
using the chlorideanalog of CTAB: cetyltrimethyl-
ammonium chloride, CTAC [28]. The advantage of
Phan Thi Thanh Binh K52 Advanced Program Chemistry
this method is that nanocube size could be adjusted simply by varying the amount of

seeds added to the growth solution, obtaining cubes with edge lengths ranging from 38
± 7 nm to 269 ± 18 nm width at high yield up to 95%.
Besides, nano - gold has been found in other various shapes and sizes such as
tetrahexahedra, rhombic dodecahedra, obtuse triangular bipyramids (Fig. 14)
synthesized by a number of methods.
Figure 14: Complex nanostructures
In brief, Table 2 covered approaching methods to make gold nanoparticles:
Table 2: Summary of synthetic approaches to obtain various gold nanostructures
Phan Thi Thanh Binh K52 Advanced Program Chemistry
Au nanoform Approached methods Authors
Nanospheres Citrate - mediate reduction J. Turkevich at al. (1951)
G.Frens (1973)
Nanorods (colloidal) Seeded growth (CTAB) C.J. Murphy (2001)
B. Nikoobak & El-Sayed (2003)
Nanoshells Overgrowth of core - bound particles N.J. Halas (1998)
Hollow nanospheres
Overgrowth of core - bound particles,
galvanic displacement Z.Liang (2003)
H. - P. Liang & L. Jiang (2005)
Nanocages/frames
PVP - stabilized polyol, galvanic
displacement Y. Xia (2002, 2006)
Nanocubes/octahedra
PVP - stabilized polyol, seeded
growth (CPC/CTAC) W. Niu (2008), Jang (2010)
Icosahedra/tetrahedra
PVP - stabilized polyol, seeded
growth (CTAC) F. Kim (2004)
J. Zhang (2008, 2010)
Nanoprisms Biosynthesis seed growth (CTAB) S. Shankar (2004)

J.E. Millstone (2005)
Tetrahexahedra Seeded growth (CTAB) T. Ming (2009)
Obuse triangular
bipyramids Seeded growth (CTAC)
M.L Personick, M.R Langille
(2011)
Rhombic dodecahedra Seeded growth (CPC/CTAC) W. Niu (2008)