Journal of Magnetism and Magnetic Materials 394 (2015) 173–178

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Journal of Magnetism and Magnetic Materials

journal homepage: www.elsevier.com/locate/jmmm

Recent advances in the synthesis of Fe3O4@AU core/shell nanoparticles

Sergei V. Salihov a, Yan A. Ivanenkov c, Sergei P. Krechetov c, Mark S. Veselov c,
Natalia V. Sviridenkova a, Alexander G. Savchenko a, Natalya L. Klyachko a,b,
Yury I. Golovin b, Nina V. Chufarova c, Elena K. Beloglazkina a,b, Alexander G. Majouga a,b,n
a
National University of Science and Technology MISiS, Leninskiy, Building 9, Moscow, 119049, Russian Federation,
b
Moscow State University, Chemistry Department, Lenins kie gory, Building 1/3, GSP-1, Moscow, 119991, Russian Federation
c
Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region, 141700, Russian Federation

art ic l e i nf o a b s t r a c t

Article history: Fe3O4@Au core/shell nanoparticles have unique magnetic and optical properties. These nanoparticles are
Received 9 November 2014 used for biomedical applications, such as magnetic resonance imaging, photothermal therapy, controlled
Received in revised form drug delivery, protein separation, biosensors, DNA detection, and immunosensors. In this review, recent
1 April 2015
methods for the synthesis of core/shell nanoparticles are discussed. We divided all of the synthetic
Accepted 4 June 2015
methods in two groups: methods of synthesis of bi-layer structures and methods of synthesis of mul-
Available online 20 June 2015
tilayer composite structures. The latter methods have a layer of “glue” material between the core and the
Keywords: shell.
Magnetite & 2015 Elsevier B.V. All rights reserved.
Core/shell nanoparticles
Biomedical applications
Nanoparticle synthesis
Gold coated iron oxide nanoparticles.

1. Introduction
Many types of magnetic nanoparticles (MNPs) have been syn-
thesized over the past decade. There are a number of recent re-
views that describes the synthesis and biomedical applications of
MNPs [1–5]. The most important features of MNPs for biomedical
applications are:
(1) Superparamagnetism to prevent aggregation;
(2) Good magnetic responsiveness for separation and delivery,
which is controlled by an external magnetic field;
(3) Appropriate particle size for optimized electrical, optical, and
magnetic properties of MNPs;
(4) Good dispersion, stability, and biocompatibility to avoid mac-
rophage endocytosis and to extend blood circulation time;
(5) Appropriate surface for functionalization.
Different MNPs have different properties, methods of synthesis
and applications. Among these MNPs are Mn3O4, Co, Ni, NiO, Nd
and others [6–9]. Iron oxides are the most commonly used MNPs
because of the toxicity and rapid oxidization of the other MNPs
[10]. Surface modifications of MNPs are very important for medical
applications, including magnetic resonance imaging, controlled
drug delivery, photothermal therapy, protein separation and im-
munoassays [11–17].
However, there are some disadvantages of uncoated iron oxide
nanoparticles for biological applications:

Their instability under physiological conditions [18]

Formation of harmful free radicals promoted by them [19]

Inappropriate surface binding of the ligand, which results in
failure in controlled drug delivery [20]

There are many different approaches to the modification or

Abbreviations: MNP, magnetic nanoparticles; TEM, transmission electron micro- functionalization of the MNPs surfaces with different materials
scopy; CTAB, cetyltrimethylammonium bromide; PZS, polyphosphazene; PEI,
polyethyleneimine; PB, Prussian Blue; PANI, polyaniline; PDADMAC, poly(dia-
such as polymers, organic monolayers, oxides, and metals. One of
llyldimethylammonium chloride); MRI, magnetic resonance imaging; DLS, dynamic the most promising modifications is adding a gold shell. Gold
light scattering; PSS, poly-(sodium 4-styrenesulfonate) nanoparticles are commonly used in biomedical applications due
n
Corresponding author at: Moscow State University, Chemistry Department,
to their simple synthesis, possibility of bioconjugation and good
Leninskie gory, Building 1/3, GSP-1, Moscow, 119991, Russian Federation.
E-mail addresses: chnv@pharmcluster.ru (N.V. Chufarova), biocompatibility [21]. Moreover, gold nanoparticles are already
majouga@org.chem.msu.ru (A.G. Majouga). used for drug delivery [22]. One of the most important properties

http://dx.doi.org/10.1016/j.jmmm.2015.06.012
0304-8853/& 2015 Elsevier B.V. All rights reserved.
174 S.V. Salihov et al. / Journal of Magnetism and Magnetic Materials 394 (2015) 173–178

of gold nanoparticles is so called “surface plasmon”, which results

in significant optical absorption in the visible and near-infrared
region. The optical properties of Fe3O4@Au nanoparticles are de-
sired in biological applications, such as imaging and photothermal
therapy. However, Fe3O4@Au nanoparticles are of low solubility in
water [23]. This low solubility leads to the aggregation and pre-
cipitation of nanoparticles, which is unsuitable for biomedical
applications [24]. For improved solubility in water, the surface of
Fe3O4@Au nanoparticles may be functionalized with hydrophilic
thiols [25,26].
One of the most challenging issues in core/shell MNPs efficacy
is the need to overcome biological barriers to reach their target,
such as tumours. Major clearance routes for these MNPs, according
to their physicochemical properties, are the liver, spleen and kid-
neys. Particles must be able to evade clearance to be delivered to a
tumour. Thus, their physiochemical properties, including size,
charge, surface properties and morphology, must be precisely
controlled [27].
In our previous work we described the distinct effect of non-
heating super-low-frequency magnetic fields as well as radio-fre-
quency magnetic fields on the kinetics of chemical reactions cat-
alysed by the enzymes immobilized on Fe3O4@Au MNP aggregates.
Exposure to an alternating current magnetic field resulted in a
reduction in enzyme activity. This observation suggests the sig-
nificance of magneto-mechanochemical effects induced by the
realignment of MNP magnetic moments in an alternating current
Fig. 1. Schematic representation of three different techniques for the synthesis of
magnetic field rather than traditional heating [28]. Fe3O4@Au core/shell nanoparticles.
In this article, we discuss the work on the synthesis and char-
acterization of Fe3O4@Au nanoparticles for a biomedical applica-
tion that has occurred since 2006. We exclude the methods of added, followed by the addition of sodium citrate as a reducing
synthesis of dumbbell, cluster/shell nanoparticles and iron oxide agent for Au shell formation. L-Homocysteine was added to the
MNPs with Au seeds on the surface; other methods are described boiling solution to form Fe3O4@Au@homocysteine nanoparticles
in other excellent reviews [29–31]. [23,35,45]. These nanoparticles are well dispersed in water, which
is essential for biomedical applications. Moreover, the surface
functionalization with homocysteine is useful for the further
2. Synthesis of Fe3O4@Au core/shell nanoparticles: typical functionalization of the Fe3O4@Au nanoparticle surface. Amine
approaches. and carboxylate groups on the nanoparticle surface may allow
subsequent transformations, as was shown for a Au nanoparticle
During the last few years, many articles have described effec- ligand sphere [47] and for carboxylated Fe3O4@Au nanoparticles
tive chemical techniques to synthesize stable monodispersed [45]. According to transmission electron microscopy (TEM) data,
Fe3O4@Au nanoparticles with the required size. The surface of the the nanoparticles are nearly spherical in shape, with small average
nanoparticles could be further functionalized to produce pro- sizes (12.3 nm [23] and 22 nm [35]). Fe3O4 nanoparticles can also
spective structures for biomedical applications. The most common be coated with gold using the NaBH4 reduction of HAuCl4 in a
synthetic methods for core synthesis are described in other ex- sonicator. The sonication procedure leads to improved nano-
cellent reviews [32–34]. These methods include co-precipitation, particle monodispersity and prevents agglomeration due to ionic
thermal decomposition, reversed micelle technique and the sol- interactions. The resulting core/shell nanoparticles are also small,
vothermal method. There are two types of Fe3O4@Au nano- with an average size of 12.5 7 3 nm, according to transmission
particles: bi-layer and multilayer composite structures (Fig. 1). Bi- electron microscopy (TEM) images [37]. Hydroxylamine hydro-
layer structures, which are the standard structures, consist of two chloride can also be used as a reducing agent. The next approach
layers: the core and Au shell. Multilayer composite structures to the coating of Fe3O4 with gold is HAuCl4 reduction using sodium
consist of more than two layers. Typically, there are three layers: citrate and hydroxylamine hydrochloride. This reduction process
the core, the “glue” material (SiO2, polymers, etc.) and the Au shell. requires a longer time than other methods [23,35,37] and took up
There are two different approaches to the synthesis of Fe3O4@Au to 5 h. The resulting nanoparticles were spherical in shape, with
nanoparticles. The first approach is used to produce bi- layer an average diameter of 20 nm. [38] Subsequently, Fe3O4@Au na-
structures (Scheme I), and the second approach is used for mul- noparticles were functionalized with 11-mercaptoundecanoic acid
tilayer composite structures (Scheme II). and 11-dodecanethiol (Table 1). HAuCl4 reduction with sodium
citrate and hydroxylamine hydrochloride may be performed in
two steps. First, sodium citrate was added to Fe3O4, and the so-
3. Synthesis of Fe3O4 bi-layer structures (Scheme I) lution was stirred before NH2OH  HCl and HAuCl4 were added.
This process took up to 30 min. [48] Next, Fe3O4@Au were mod-
One of the most common methods of the synthesis of ified with 3′-(alkanethiol) oligonucleotides and used for detection
Fe3O4@Au core/shell nanoparticles is the formation of a gold shell of DNA point mutations. The average diameter of the core/shell
directly onto the magnetite surface [11,23,35–45]. For example, nanoparticles was 100 nm [48].
small Fe3O4 (9–20 nm) nanoparticles were first synthesized using The magnetite surface is often modified to attract Au ions. One
the co-precipitation of FeCl2 and FeCl3 in diluted NH3 solution. of the modifications is a sodium citrate coating of Fe3O4. Fe3O4@Au
Next, a HAuCl4 solution was boiled and Fe3O4 nanoparticles were nanoparticles with a diameter of 15–40 nm were obtained using
Table 1
Summary comparison of the synthetic methods.

Core/shell Scheme Synthesis techniques Size, nm Surface modification Application Refs.

Core Shell Core Particle

Fe3O4@Au I Co-precipitation Reduction by citrate N/A 30 Homocysteine Unspecified [36]

20 22 (2 nm gold T2 Contrast Agent in MRIa [35]
shell)
N/A 12.3 (0,5 nm Unspecified [23]
gold shell)
Reduction by NaBH4 Ultrasound 9.5 7 3 12.5 7 3 Boronic oxide Boronic oxide þ Biomolecule immobiliza- [37]
fructose tion and detection
Reduction by hydroxylamine hydrochloride and N/A 20 11-mercaptoundecanoic acid 11- Interaction with target [38]

S.V. Salihov et al. / Journal of Magnetism and Magnetic Materials 394 (2015) 173–178
citrate dodecanethiol molecules
N/A 100 3′-(alkanethiol) oligonucleotide Biosensor [48]
Co-precipitation Citrate Reduction by citrate 11 7 3.2 (DLSb) 24.06 7 1.5 Thiol-terminated polyethylene Doxorubicin delivery [11]
coating (10–15 nm glycol
gold shell)
(DLS)
10 22-30 (12– 3′-alkanethiol- DNA detection [39]
20 nm gold modifiedoligonucleotides
shell)
N/A 15–40 Proteinimmunoglobulin G Biological separations [40]
Reduction by hydroxylamine N/A 30 Different antibodies and proteins Ultrasensitive detection [41]
of carbohydrate-protein
interactions
Thermal decomposition Thermal decomposition from Au(Ac)3, oleic acid 6.7 7 0.7 9.2 7 1.3 Thiolated DNA Unspecified [42]
and oleylamine (organic medium) (1 nm gold
shell)
Reduction byoleylamine (organic medium) 10 12 (1 nm gold No Unspecified [43]
shell)
Reversed micelle technique Reversed micelle technique Reduction by NaBH4 N/A 187 4 No T1 and T2weighted [44]
imaging
6 4–22 (3 nm 11-mercaptoundecanoic acid and DNA sensors [45]
gold shell) streptavidin
Water-in-oil inverse nano- Reduction by NaBH4 9 7 2 137 3 (3–4 nm No Unspecified [46]
emulsion procedure gold shell)
Fe3O4@PZS@Au II Ultrasonic irradiation Facile one-step polymerization Reduction by 8.2 7 1.1 (Fe3O4) 253 7 20 (3 nm No MRI and photothermal [51]
NaBH4 228.5 7 15 Au NPs) therapy
(Fe3O4@PZS)
Fe3O4@PEI@Au From FeSO4 and KNO3, in Reduction by NH2OH  HCl 20 307 5 (4 7 Nitrilotriacetic acid, Ni2 þ Bioseparation and [52]
the presence of PEI (cube 1 nm Au NPs) analysis
Fe3O4@PEI@Au Fe3O4 shape) N/A 50–150 (2 nm No Unspecified [53]
Au NPs)
Fe3O4@Polyaniline@Au Solvothermal method Re- Reduction by NaBH4 170 3 (Au NPs) No Unspecified [54]
duction by ethylene glycol
Fe3O4@PB@Au Co-precipitation PB and bo- Reduction by citrate Less than 10 80(1–3 nm Au Horseradish peroxidase, glucose Electrochemical [55]
vine serum albumin coating NPs) oxidase and antibody biomolecules immunosensors
Fe3O4/Fe2O3@SiO2@Au Co-precipitation Silica coat- Reduction by L-ascorbic acid 170 206 (15 nm Au No Unspecified [50]
ing, three polyelectrolyte NPs)
layers: PDADMAC, PSSc,
PDADMAC

a
MRI – magnetic resonance imaging
b
DLS – dynamic light scattering
c
PSS – poly-(sodium 4-styrenesulfonate)

175
176 S.V. Salihov et al. / Journal of Magnetism and Magnetic Materials 394 (2015) 173–178
this approach. In this case, magnetite nanoparticles were synthe-
sized via the co-precipitation method. Before the precipitate was
rinsed, sodium citrate was added, and then, the solution was
stirred [11,39,40]. A HAuCl4 solution was heated until boiling, and
then, Fe3O4 citrate coated nanoparticles were added to the solu-
tion [11,39]. The other modification of this method is the sonica-
tion of Fe3O4 and citrate and then heating until boiling before the
addition of HAuCl4. This reaction continued for 15 min. after the
addition of Au3 þ salts [40]. Additionally, sodium citrate can be
added after the precipitate was rinsed. In this case, the solution
was stirred overnight to exchange adsorbed OH– with citrate an-
ions [41], which is much longer than in the methods of [11,39,40].
Subsequently, HAuCl4 was added using hydroxylamine as a redu-
cing agent.
The described reactions are rapid and convenient because they
are performed in aqueous solution. However, there are also other
methods of Fe3O4@Au synthesis in organic media. For example,
small Fe3O4 nanoparticles with a diameter of 10 nm [43] and
6.7 70.7 nm [42] were synthesized using the thermal decom-
position method. The reduction of Fe(acac)3 by 1,6-hexadecanediol
in the presence of oleic acid and oleylamine as capping agents
resulted in the formation of Fe3O4 nanoparticles with amine
functional groups on the surface. Thus, these amine groups were
used as a template to attach Au3 þ ions. In one case, the Au shell
was formed by reduction of Au(Ac)3 using 1,2-hexadecanediolin in
the presence of oleic acid, oleylamine and magnetite. The solution
was heated to 180–190 °C and held at this temperature for 1.5 h To
make water-soluble core/shell nanoparticles, they were dissolved
in TMAOH and tri-sodium citrate solution. [42] In another ex-
periment, the Au shell was formed via the reduction of HAuCl4 by
oleylamine in the presence of magnetite [43].These nanoparticles
dispersed well in nonpolar solvents. To make water-soluble core/
shell nanoparticles, the nanoparticles were dissolved in cetyl-
trimethylammonium bromide (CTAB) and a sodium citrate aqu-
eous solution under sonication. The as-prepared nanoparticles
were used as seeds for the continued growth of the Au shell using
ascorbic acid reduction of HAuCl4 for 6 h to deposit an extra
0.5 nm layer of gold. Thus, the obtained nanoparticles have a core
diameter of 10 nm and shell diameters of 1 nm, 1.5 nm, 2 nm,
2.5 nm, and 3 nm [43]. This method takes a longer time than the
reduction using citrate or hydroxylamine described above and
requires temperature control. However, the method allows for
control of the thickness of the Au shell. The dissolving in different
solutions is required to make Fe3O4@Aunanoparticles water-
soluble.
The other group of synthetic methods is reverse micelle tech-
niques. In the first experiment, Fe3O4@Au nanoparticles were
synthesized using the reverse micelle reaction under argon; CTAB
was used as the surfactant, octane as the oil phase, and 1-butanol
as the co-surfactant. The Fe cores were prepared from FeSO4 by the
reduction of Fe2 þ with NaBH4. To create a gold shell on the Fe core,
HAuCl4 was prepared as a micelle solution and then added to the
solution of FeSO4 and NaBH4. The solution was kept stirring at
room temperature overnight. The diameters of the resultant na-
noparticles were 18 74 nm and 4–22 nm ([44] and [45], respec-
tively). The authors found that the Au shell does not protect the
core against oxidation [44]. According to Mössbauer studies, the
product of oxidation appeared to be γ-Fe2O3 [49].
Fe3O4@Au core/shell nanoparticles are also synthesized via pre-
adsorbed Au seeds. In this method, Au seeds attach to the surface
of magnetite nanoparticles. The magnetite nanoparticles serve as
nucleation sites for the shell formation with Au3 þ and a reducing
agent. This method is described by H. Maleki et al. [46]. In their
work, they prepared Fe3O4 nanoparticles using the reverse micelle
technique. Toluene was used as the oil phase with cetyl-
trimethylammoniumbromide as the surfactant and 1-butanol as
the co-surfactant. Subsequently, magnetite nanoparticles were
dispersed in an acidic solution to produce positive charges on their
surface. The Au shell was obtained by reduction with NaBH4. The
excess of NaBH4 introduces a negative charge to the surface of the
Au seeds. This negative charge prevents aggregation of the seeds
and also attracts them to the magnetite surface via electrostatic
interaction [46]. Thus, Fe3O4@Au were synthesized in a single step
and a one-pot procedure using Au seeds as the nucleation sites.
The diameter of the nanoparticles is 13 73 nm, with a core dia-
meter of 9 72 nm.
4. Synthesis of Fe3O4@“glue”@Au multilayer composite
structures
The above-mentioned Fe3O4@Au structures are bi-layer mate-
rials. The methods of multilayer composite structures are different
from those described above. Multilayer structures have a “glue”
layer between magnetite and a gold shell. There are many mate-
rials that serve as the “glue”: silica [50], polymers [51–54] and
other materials [55]. The design and preparation of the “glue”
layer is essential to obtain multifunctional nanoparticles. The
“glue” layer should stabilize Fe3O4 nanoparticles and prevent them
from aggregation. The “glue” should also have metal binding
groups to attach gold seeds to construct nucleation sites for shell
growth. In addition, the “glue” must be biocompatible and have
thermal stability.
Zhou et al. [56] proposed using polyphosphazene (PZS) as the
“glue” material because it is rich in N, P, and S atoms and has many
phenolic hydroxyl groups to interact with gold. Fe3O4 nano-
particles were synthesized from an iron precursor, iron(III) acetyl
acetonate (Fe(acac)3) in the polyol medium triethylene glycol at
elevated temperatures. A mixture of hexachloro-cyclotripho-
sphazene, triethylamine and magnetite in the presence of tetra-
hydrofuran maintained via ultrasonic irradiation. Next, sulpho-
nyldiphenol was added, and then, irradiation continued for 6 h.
The obtained Fe3O4@PZS nanoparticles were added to HAuCl4.
After ultrasonication of the mixture for 30 min, an excess of NaBH4
and sodium citrate were added. In the gold shell growth step,
HAuCl4 and Na3Ct were added to an aqueous solution of
Fe3O4@PZS@Au seeds [51]. According to TEM images, the dia-
meters of the obtained Fe3O4, Fe3O4@PZS, and Fe3O4@PZS@Au
were 8.2 7 1.1 nm, 228.5 715 nm, and 253 720 nm, respectively.
Polyethyleneimine (PEI) is often used for biomedical applica-
tions as well as a “glue” material because every third atom of PEI is
a proton containing amino nitrogen atom [57].
Fe3O4@polyethyleneimine (Fe3O4@PEI) nanoparticles were syn-
thesized from FeSO4 and KNO3 in the presence of PEI. The obtained
nanoparticles had a cubic shape and size of 50 nm [53] and 20 nm
[52]. Next, the Fe3O4@PEI suspension was sonicated and stirred
with colloidal gold nanoparticles. Gold nanoparticles were ob-
tained from HAuCl4 with NaBH4 and sodium citrate reduction. The
Fe3O4@PEI@Auseeds particle surface was then functionalized again
with PEI. Au shells were grown by reduction of HAuCl4 by
NH2OH  HCl [52,53]. The obtained nanoparticles had good mono-
dispersity, exhibiting size distributions of 50–150 nm [53] and
3075 nm [52].
Another prospective “glue” material is Prussian Blue (PB). PB
could accelerate the electron transfer between the electrode and
the enzymes, which is essential for biosensing [58]. Together with
good biocompatibility and hydrophilic properties, PB enables
Fe3O4@PB nanoparticles to be produced for biomedical applica-
tions [59,60]. For the synthesis of Fe3O4@PB@Au nanoparticles,
Fe3O4 nanoparticles were obtained using the co-precipitation
method. Fe3O4@PB were prepared from K3[Fe(CN)6] and FeCl3 in
the presence of HCl using Fe3O4 as seeds. Next, nanoparticles were
 S.V. Salihov et al. / Journal of Magnetism and Magnetic Materials 394 (2015) 173–178
modified with bovine serum albumin to obtain amine and dis-
ulphide groups on the surface of the nanoparticles. Subsequently,
Fe3O4@PB covalently attracted gold seeds, which then serve as
nucleation sites for gold shell formation via citrate reduction. The
obtained magnetite nanoparticles were less than 10 nm in size,
with Fe3O4@PB@Au produced having a diameter of 80 nm [55].
Polyaniline (PANI) is also used as a “glue” material. Magnetite
nanoparticles coated with PANI were demonstrated to be para-
magnetic and therefore a prospective material for biomedical ap-
plications, such as enzyme immobilization, nucleic acid extraction,
cancer diagnosis, biosensors, and drug delivery [61]. In this work,
Fe3O4 nanoparticles were synthesized through a solvothermal
method and then dissolved in water. Next, aniline was added in
the presence of HCl. The solution was shaken for 12 h. Ammonium
peroxodisulphate was added to start the oxidative polymerization
under ultrasonic irradiation. Sonication of Fe3O4@PANI and an
acetic acid solution induced positive charges at the surface of
theFe3O4@PANI nanoparticles. Au seeds were immobilized on the
surface of Fe3O4@PANI nanoparticles due to electrostatic attraction
under sonication. Finally, the Au shell was formed via reduction
with NaBH4. The diameter of magnetic core was 170 nm, with a
gold shell thickness of 3 nm [54].
SiO2 is widely used for an Fe3O4/γ-Fe2O3 coating for biomedical
applications [30,32]. Salgueirino-Maceira et al. [50] used silica as
the “glue” material for iron oxide/gold core/shell nanoparticles. In
this work, Fe3O4/γ-Fe2O3 nanoparticles were prepared using the
co-precipitation technique. Aqueous dispersions of magnetite na-
noparticles that were partially oxidized to maghemite were ob-
tained. Fe3O4/γ-Fe2O3@SiO2 nanoparticles were prepared from
tetraethyl orthosilicate in the presence of NH4OH. A polyelec-
trolyte layer was deposited using the alternating adsorption of
poly(diallyldimethylammonium chloride) (PDADMAC), poly-(so-
dium 4-styrenesulfonate), and PDADMAC onto the silica spheres in
a manner that the polymer selected has an opposite charge to that
on the silica spheres. The polymers were adsorbed through elec-
trostatic interactions. These three layers of polyelectrolytes pro-
duce a smoother, more uniform, and positively charged surface on
the Fe3O4/γ-Fe2O3@SiO2 nanoparticles. The Au seeds were at-
tracted onto the surface of the nanoparticles via electrostatic in-
teractions. The gold shell was formed via reduction of HAuCl4 with
ascorbic acid.
5. Conclusions and outlook
The synthesis of multifunctional nanomaterials for biomedical
applications is one of the most challenging issues. These materials
must be biocompatible and have a surface that is appropriate for
modification. Magnetite nanoparticles should be covered with a
shell material to overcome the instability and toxicity of the in-
trinsic nanoparticles. Gold is a promising shell material because of
its good biocompatibility, its ability to enable surface modifica-
tions and its “surface plasmon” property. Gold nanoparticles are
used for many biomedical applications, including MRI, protein
purification and separation, tumour targeting, photothermal
therapy, and so on. In this review, we summarized the recent
methods of synthesis of Fe3O4@Au core/shell nanoparticles. Gen-
erally, two synthetic methods are used. The first method is used
for the synthesis of bi-layer nanoparticles, and the second method
is used for multilayer composite nanoparticles. Magnetite nano-
particles are synthesized via co-precipitation, thermal decom-
position, the inverse micelle technique, or the solvothermal
method. These magnetite nanoparticles are often modified with
citrate or hydroxylamine to attract Au ions. One of the described
methods enabled the control of the Au shell thickness; nano-
particles with 1 nm, 1.5 nm, 2 nm, 2.5 nm and 3 nm shell
177
thicknesses were obtained [43].
Media for the synthesis of core/shell nanoparticles can be
aqueous or organic. In organic media, the presence of oleic acid
and oleylamine leads to the formation of magnetite nanoparticles
with amine groups on the surface. Amine groups served as a
template to attach Au ions. Pre-adsorbed Au ions can also act as
nucleation sites for Au shell growth with Au ions and a reducing
agent [46]. In the second method, Fe3O4 nanoparticles, after their
synthesis, are covered with a “glue” layer to stabilize the cores and
to prevent their aggregation. Metal binding groups of the “glue”
material can attach gold to create nucleation sites for shell for-
mation. The most prospective “glue” materials are considered to
be PZS, PEI, PB, PANI and SiO2.
Although there are many different methods for core/shell na-
noparticle synthesis, considerable challenges and issues remain to
be solved. Nanoparticles must be well dispersed and hetero-
geneous. These nanoparticles also must have good solubility in
water to be used for biomedical applications. Functionalization of
the surface of nanoparticles is also challenging. Furthermore, the
purity and stability of the nanoparticles in physiological environ-
ments are essential [62]. Therefore, further development of the
methods of synthesis and the surface modification is desirable for
the use of nanoparticles for biomedical applications.
Acknowledgements
The authors gratefully acknowledge the financial support of the
Ministry of Education and Science of the Russian Federation in the
framework of the Increased Competitiveness Program of NUST «MISiS»
(No. K1-2014-022) and Russian Scientific fund RSF 14-13-00731.
Appendix A. Supplementary material
Supplementary data associated with this article can be found in
the online version at http://dx.doi.org/10.1016/j.jmmm.2015.06.
012.
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