Review

Ferrite-based magnetic nanouids used in hyperthermia applications

Ibrahim Shari, H. Shokrollahi
n
, S. Amiri
Electroceramics Group, Department of Materials Science and Engineering, Shiraz University of Technology, Shiraz, Iran
a r t i c l e i n f o
Article history:
Received 11 July 2011
Received in revised form
27 September 2011
Available online 28 October 2011
Keywords:
Ferrite
Hyperthermia
Magnetic property
Magnetic nanouid
a b s t r a c t
Magnetic ferrouids (magnetic nanouids) have received special attention due to their various
biomedical applications such as drug delivery and hyperthermia treatment for cancer. The biological
applications impose some special requirements. For example, the well-known iron oxide ferrouids
become undesirable because their iron atoms are poorly distinguishable from those of hemoglobin. A
conceivable solution is to use mixed-ferrites (MFe
2
O
4
where MCo, Mn, Ni, Zn) to have a range of
magnetic properties. These ferrites have attracted special attention because they save time, and
because of their low inherent toxicity, ease of synthesis, physical and chemical stabilities and suitable
magnetic properties. Based on the importance of ferrite particles in ferrouids for hyperthermia
treatment, this paper gives a summary on the physical concepts of ferrouids, hyperthermia principal,
magnetic properties and synthesis methods of nanosized ferrites.
& 2011 Elsevier B.V. All rights reserved.
1. Introduction
In any discussion of uids with magnetic properties, it is
convenient to divide them into the following categories:
(A) ferrouids; (B) magnetorheological uids; (C) dispersions of
micron-sized particles of a non-magnetic material containing
magnetic nanosized particles and (D) uids containing paramag-
netic particles.
Ferrouids are the colloidal suspensions related to surface-
modied magnetic nanoparticles (220 nm) dispersed in a uid
carrier (Fig. 1; [1]) [24]. The applicable elds are divided into some
biomedical categories: the cancer treatment by hyperthermia [5],
MRI contrast agent [6], drug delivery [7], DNA hybridization [8] and
cell separation [9]. To achieve the ferrouid behavior for a material,
there exist two ways: in one of them the ferromagnetic materials
can be heated until it reaches the liquid. However, they lose their
ferromagnetic behavior because the Curie point is lower than the
melting point [10]. The only exception, undercooled melts of Co-Pd
alloys, found to show a magnetic phase transition in 1996 is of no
technical importance concerning magnetic eld controlled ows
and related applications [10]. Another way is to synthesize a colloid
using very ne particles.
The syntheses of magnetic uids consist of two steps: (a) the
preparation of the nanosized magnetic particles that can be
produced by microemulsion [11], co-precipitation [12], ball
milling [13], sonochemical [14], solgel [15] and thermal decom-
position [16]. (b) The subsequent stabilization/dispersion of the
nanoparticles in various non-polar or polar carrier liquids [17], in
which magnetic nanoparticles can be coated by some methods
such as co-precipitation [12], coreshell [18,19], micro-emulsion
[20,21] and then levitated in the carrier liquid. To obtain a stable
ferrouid, dispersants [22,23] must be chosen to match the
dielectric properties of the carrier liquid. Various surfactants,
e.g. sodium oleate, dodecylamine, sodium carboxy-methylcellu-
lose, are usually used to enhance dispersibility in an aqueous
medium [24].
Historically, the rst magnetic nanoparticle used in magnetic
uids was magnetite (Fe
3
O
4
), in 1960 by NASA [25,26], but
different types of magnetic material include the following:
Ferrites: MFe
2
O
4
(MMn, Ni, Co, Zn, Fe) [22,27,28], g-Fe
2
O
3
[29]
and some alloys such as FePt, NiPt and NiPd [30,31], which can be
used in the magnetic uid. Although pure metals (Fe, Co, Ni)
possess the highest saturation magnetization, they are highly
toxic and extremely sensitive to oxidation then without a further
appropriate surface treatment such pure metal nanoparticles are
not relevant for biomedical applications [32]. In contrast, iron
oxides are less sensitive to oxidation and, therefore, can give a
stable magnetic response. In fact, small iron oxide nanoparticles
have been applied to in vitro diagnosis for about 50 years. Recent
studies have demonstrated that magnetite (Fe
3
O
4
) and maghe-
mite (g-Fe
2
O
3
) are very promising candidates due to their bio-
compatibility and relative ease to functionalize [33,34]. However, in
order to achieve more safety for biomedical applications, iron oxide
nanoparticles must be covered by an organic or inorganic biocom-
patible coating. These coatings include polyethylene glycol, poly-
ethylene glycol fumarate, polyvinyl alcohol, acrylate-based coatings,
dextran-based coatings, synthetic polyesters, alginate, chitosan and
polyethylenimine, gold and silica [35].
Contents lists available at SciVerse ScienceDirect
journal homepage: www.elsevier.com/locate/jmmm
Journal of Magnetism and Magnetic Materials
0304-8853/$ - see front matter & 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jmmm.2011.10.017
n
Corresponding author. Tel.: 98 711 7353509; fax: 98 711 7354520.
E-mail address: Shokrollahi@sutech.ac.ir (H. Shokrollahi).
Journal of Magnetism and Magnetic Materials 324 (2012) 903915
By adding other ions such as Ni
2
, Mn
2
and Co
2
to Fe
3
O
4
,
ferrites having a range of magnetic properties can be obtained. This
exibility can be used to tune the magnetic properties for
hyperthermia applications by creating cubic mixed-ferrite material.
These ferrites have attracted special attention because they save
time, have low inherent toxicity, ease of synthesis and their physical
and chemical stabilities [36]. In all cases, however, issues of
biocompatibility and toxicity limit the choice of materials; however,
the use of coatings may make the use of these materials feasible.
It would be worth mentioning that due to the importance of
biomedicine in our life, this paper investigates a physical concept
of ferrouids and the most important ferrites, which are regarded
as magnetic cores used in the hyperthermia application.
2. Physical concepts of ferroouids
2.1. Inter-particle interactions
An important factor in the application of ferrouids is their
colloidal stability. Stability is determined by the balance between
various forms of energy (attractive and repulsive forces) and
thermal energy (k
B
T) to avoid segregation over a period of time
after the eld is removed (Table 1). If the average thermal energy
exceeds the sum of the total interactions (barrier energy) a
negligible agglomeration will occur. Depending on the particle
volume fraction, size distribution, temperature and applied mag-
netic eld the aggregation will occur in ferrouid [37].
When the A constant becomes zero means no agglomeration
between the surfactant molecules will occur (similar dielectric
properties between the carrier liquid and the tail). It can be
shown that a surfactant layer of 2 nm thickness yields a steric
repulsion strong enough to avoid the direct contact between the
magnetic particles, thereby preventing the inter-particle agglom-
eration (Fig. 2) [10]. The steric repulsion force results from the
reduction of the conguration room of the surfactant molecules,
is much more short-ranged and operates at distances of the
overlap of the surface layers. A surfactant layer consisting of long
chain molecules with a polar head and an unpolar tail prevents
the adhesion due to van der Waals forces. This force depends on
the inter-particle distance and the thermal energy cannot re-
disperse the particles being in contact.
Therefore, in the ferrouids a relatively narrow distribution of
small coated particles is important. The morphology and size of
the coated magnetic particles of the different ferrouids are
shown in Fig. 3 [38,39]. From the TEM micrographs, it is obvious
that the particles are nearly spherical in shape and are generally
well dispersed.
2.2. Heat dissipation mechanisms
Heat dissipation from the small magnetic particles is caused by
the delay in the relaxation of the magnetic moment through
either the rotation within the particle (Ne el) or the rotation of the
particle itself (Brownian, viscous loss). These relaxation mechan-
isms are discussed when the magnetic particles are exposed to an
AC magnetic eld with the magnetic eld reversal times shorter
than the magnetic relaxation times of the particles. The Ne el (t
N
)
and Brownian (t
B
) magnetic relaxation times of a particle are
given by the following equations [42,43]:
t
N
t
0
expKV
M
=k
B
T 1
t
B

3V
hyd
k
B
T
Z 2
Fig. 1. Mechanism of the formation of colloidal suspension [1].
Table 1
Various forces acting in a ferroouid [17, 37, 40, 41].
Interaction force Equation Ferrouid stability criteria Description Particle type
Magnetic eld energy 9E
mag
9m
0
M
0
VH
kT=m
0
MHV Z1,dr
6kt
pm
0
MH

1=3
(Attractive) Uncoated
particles
Gravitational eld Egrav DrVgh
DrgL
m
0
MH
51
Attractive Uncoated
particles
Dipoledipole contact energy
E
dip
m
0
M
2
0
=12V: 12kT
m
0
M
2
V
Z1,dr
72kT
pm
0
M
2

1=3
Attractive Uncoated
particles
Dipoledipole un-contact
energy
nr
ij
,m
i
,m
j
nsr r
ij

1
r
3
ij
m
i
m
j

3m
i
:r
ij
m
j
:r
ij

r
2
ij
" #
Attractive Uncoated
particles
Van der Waals
E
vdW

A
6
2
l
2
4l

2
l 2
2
ln
l
2
4l
l 2
2
! " #
Thermal energy cannot re-disperse the particles
being in contact and depends on the inter-particle
distance
Attractive Uncoated
particles
Steric repulsion It is much more short-ranged and operates at
distances of the overlap of the surface layers
Repulsive Coated particles
Dr: density difference between the particles and the carrier liquid, V: volume of a particle, H: external eld, g: gravitational acceleration, h: typical height of the uid
container, m
0
: magnetic constant, M
0
: spontaneous magnetization of the particle, m
i
: point dipole moment, r
ij
: inter-particle distance, n
sr
: isotropic short-range potential,
A: Hamaker constant and l: distances between the particles.
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 904
t
ef f

t
B
t
N
t
B
t
N
3
where t
N
is the Ne el relaxation time, t
B
is the Brownian relaxation
time, t
eff
is the effective relaxation time, t
0
is approximately
10
9
s, K is the anisotropy constant, V
M
is the volume of particle,
k
B
is the Boltzmann constant, T is the temperature, Z is the
viscosity and V
hyd
is the hydrodynamic particle volume [42].
From the above equations, it is obvious that the relaxation
time relies on the particle diameter. When the particles are
exposed to an AC magnetic eld with the time of magnetic
reversals less than the magnetic relaxation times of particles,
the heat is dissipated due to the delay in the relaxation of the
magnetic moment. Thus, the heat dissipation value is calculated
using the harmonic average of both relaxations and their relative
contributions depending on the particle diameter [42]. For the
superparamagnetic nanoparticles, the power loss is calculated
from Eq. (4) [44], where m is the magnetic nanoparticles (MNPs)
magnetic moment, o is the eld angular frequency, H is the AC
magnetic eld amplitude and r is the ferrite density:
P mHot
ef f

2
=2t
ef f
k
B
TrV1o
2
t
2
ef f
4
3. Hyperthermia
Cancer treatment options include surgery, chemotherapy,
radiation therapy and hyperthermia. Clinical hyperthermia falls
into three broad categories, namely (1) localized hyperthermia,
(2) regional hyperthermia and (3) whole-body hyperthermia.
Heating (4146 1C) of specic tissues or organs for tumor/cancer
therapy is named hyperthermia and can be generated by radio
frequency, microwave and laser wavelengths [4547]. Blood
vessels are poorly developed within the cancerous tissues and
have a lower thermal resistance than healthy tissue. Tumor cells
are considered more susceptible to heat than normal cells due to
their higher rates of metabolism, which makes hyperthermia a
very promising cancer treatment [32].
The cancer cell is damaged at lower temperatures than the
healthy tissue but a small section of tumor may not be heated. The
two most obvious reasons are either because of a locally increased
level of blood ow, because of a nearby blood vessel, or an
inadequate concentration of implanted magnetic nanoparticles.
The challenge in this method is to restrict local heating of the
tumor surrounding by self-control heating or by lowering the
exposure time. This goal can be partially accomplished by the
physical phenomenon of losses. It is desirable to have a high specic
loss power (SLP) heat generated per unit mass of MNPs, to achieve
the desirable temperature rise enhancement with low MNP concen-
tration. In addition to the eld parameters, specic loss power of MNP
dispersions are strongly dependent on particle size, size distribution,
anisotropy constant, saturation magnetization and surface modica-
tion [46]. The magnetic material is designed to have a Curie
temperature equal to the temperature required for hyperthermia.
It is concluded that the selection of synthesis method and
ferrite chemistry strongly affect the hyperthermia treatment. The
specic absorption rate (SAR) is expressed by Eq. (5) where C is
the specic heat of ferrouid and sample holder taken together,
DT/Dt is the initial slope of the time dependent temperature
curve, m
ferrite
is the total ferrite content in the uid [45]. Fig. 4
depicts the CoZn ferrite nanoparticles have higher magnetiza-
tion and magnetic heating loss than MnZn ferrite nanoparticles
(Eq. (4)). Hence CoZn ferrite particles can be effectively used for
the preparation of temperature sensitive ferrouid. The research
work done by Giri et al. [45] on the investigation of different soft
ferrites for hyperthermia applications is shown in Fig. 5.
Fig. 5a depicts as the magnetic eld and magnetic moment
increase the SAR parameter increases (Eq. (4)). Furthermore, Fig. 5b
Fig. 2. Schematic representation of the coated magnetic particles in a ferrouid.
The size of the surfactant molecules has not been given on the scale to make the
gure clearer [10].
Fig. 3. Intrinsic magnetic properties for various uniformly sized spinel ferrite
nanoparticles [39].
Fig. 4. Variation of saturation magnetization [65].
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 905
shows the magnetization initially increases with x up to a value of
x0.4 and then it decreases. The decrease beyond x0.4 is due to the
weakening of the AB interaction when Fe
3
is substituted by Mn
2
in the A site. Table 2 compares the SAR results of the most widely
used ferrite compounds. It is clear that the SAR value strongly
depends on the particle size, surfactant of ferrite material. For
example, in the case of Co-ferrite the highest value of SAR396
can be related to the mono-dispersed particles synthesized by
thermal decomposition method [4854]. Table 3 summarizes the
different magnetic heat generation mechanisms as a function of
average particle size:
SAR C
DT
Dt
1
m
f errite
5
4. Magnetic properties of nanosized particles
The change in magnetic properties of small ferrite particles such
as M
S
, H
C
and Curie temperature is due to the inuence of the
surface effects, cationic stoichiometry and their occupancy in the
specic sites [55]. Magnetic particles below a critical diameter
cannot support more than one domain, and are thus described as
single domain. This critical diameter is approximately 2A
1/2
/M
S
(A:
exchange constant, M
S
: moment per unit volume), and typically is
about 10100 nm for a wide range of materials. In here, the different
effective parameters on the magnetic properties of nanosized
particles will be explained.
4.1. Size effect
Magnetic properties of nanomaterials change as the ratio of
surface to volume increases. Formation of dead layer on the
surface, existence of random canting of particle surface spins,
non-saturation effect due to random distribution of particle size,
deviation from the normal cation distribution/cation site disorder,
presence of adsorbed water also result in the reduction of
magnetic properties of nanosized particles.
Fig. 6 illustrates as the particle size decreases the coercivity
increases up to single domain region and then decreases as a
result of superparamagnetic size (H
c
0) [20]. Magnetic nanopar-
ticles display the phenomenon of superparamagnetism, not
Fig. 5. Variation of SAR with (a) AC magnetic eld amplitude measured at 300 kHz for different ferrouid samples and (b) magnetization and Mn II concentration [45].
Table 2
Summary of relevant SAR determinations for ferrite nanoparticles [4854].
Magnetic compound Core diameter (nm) Corona H (kA/m) n (kHz) SAR (W/g
Fe
) Author/group
Magnetite 13 Aminosilan 13 520 146 Jordan/Felix (1999)
Magnetite 18 Dextran 16 55 57 Li-Ying/Xu-Man (2007)
Magnetite 10 6.5 400 211
a
Hilger/Kaiser (2001)
Magnetite 910 Lauric acid 15 300 168 Bahadur (2006)
Manganese ferrite 1011 Lauric acid 15 300 135.8 Bahadur (2006)
Manganese ferrite 10 Liposomes 15 300 135 Pradhan/Bahadur (2007)
Cobalt ferrite 6 Mercaptoundecanoic acid (11-MUA) 50 266 6
a
Dong-Hyun/Brazel (2008)
Cobalt ferrite 18 Suspended in gel of agarose 30 108 3.5
a
Veverka/Vasseur (2007)
Cobalt ferrite 910 Lauric acid 15 300 51.8 Bahadur (2006)
Cobalt ferrite 15 Lauric acid, dodecylamine, 1,2- hexadecanediol 5 300 396.1 Dravid (2009)
a
(W/g
Ferrite
).
Table 3
Different loss mechanisms under different average particle sizes.
Various conditions D4D
SD
DD
SD
a
D
SP
b
oDoD
SD
DD
SP
DrD
SP
c
Dominant loss mechanism/s HysteresisEddy current
d
anomalous
d
Hysteresis HysteresisNe el Brownian Ne el Brownian Brownian
a
Single domain diameter.
b
Superparamagnetic diameter.
c
In viscose medium.
d
At high frequency and high magnetic eld.
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 906
remaining magnetized after the action of magnetic eld, offering
advantage of reducing risk of particle aggregation. Superpara-
magnetic nanoparticles have been considered as attractive mag-
netic probes for biological imaging and therapeutic applications
due to two main reasons. One is the high surface-to-volume ratio,
which enables the maximum loading molecules or largest inter-
action interface. Another one is the superparamagnetic property.
Fig. 7a shows energy diagram of magnetic nanoparticles with
different magnetic spin alignments (ferromagnetism) and super-
paramagnetism in a small nanoparticle [56]. Fig. 7b and c depicts
the size dependent transition of iron oxide nanoparticles from
superparamagnetic to ferromagnetic showing TEM images and
hysteresis loops of (b) 55 nm and (c) 12 nm sized iron oxide
nanoparticles.
The expression for surface anisotropy can be simplied as
follows: K
S
6K
0
S
/d, where d is the particle size, K
S
is the surface
anisotropy energy constant [57]. Fig. 8 shows the different
conditions of surface and bulk anisotropies [58]. For K
S
K
V
20,
the calculated spin structure is collinear along Oz vertical axes,
both in the core and at the surface of the nanosphere (Fig. 8a).
Slight uctuations in spin direction can be due to the thermal
effects. For high value of K
S
, all the spins are radially oriented,
either outward or inward of the center of the nanoparticle, giving
rise to a hedgehog-type spin structure (Fig. 8d). Substitution of
ion by a more anisotropic ion, like in ferrites, can increase the
magnetocrystalline anisotropy of the inorganic core allowing for
the decrease of the magnetic particle size [59]. The reduced size of
nanoparticles results a much smaller anisotropic energy com-
pared with thermal energy, which is sufcient to invert the spin
direction. Such magnetic uctuation leads to a net magnetization
of zero, which means superparamagnetism. For example, g-Fe
2
O
3
nanoparticles of 55 nm exhibit ferromagnetic behavior with a
coercivity of 52 Oe at 300 k, but smaller 12 nm sized g-Fe
2
O
3
nanoparticles show superparamagnetism with no hysteresis
behavior [56].
4.2. Chemical composition
Magnetic properties of ferrites are directly related to the
chemical composition and distribution of the cations over tetra-
hedral and octahedral lattice sites. Since the magnetic moments
of the ions are ordered parallel within each sublattice and
antiparallel between both sublattices, the difference in the mag-
netic moments between both sublattices gives magnetic moment
to the ferrite crystal. Fig. 9 shows the hysteresis loops measured
for three MFe
2
O
4
samples (MMn, Co, Ni), which have similar
particle size (7 nm) [60]. It is clear that the magnetization for Co
ferrite is higher than the other ferrites.
4.3. Zinc effect
It should be pointed out that ZnFe
2
O
4
is less used in hyperther-
mia treatment as a pure ferrite. Zinc substituted mixed ferrites
chosen here are highly sensitive to temperature. Zinc ferrite
shows paramagnetic behavior as bulk material due to its normal
spinel structure, with Zn ions incorporated almost exclusively at
tetrahedral sites. When ZnFe
2
O
4
is prepared in the form of
nanoparticles, it becomes ferrimagnetic due to a partial migration
of Zn to the octahedral sites. [61,62,21]. This feature is generally
associated with the increase of the cation inversion and with the
diminution of the size of the grains [63]. One potential key
advantage of Zn ferrite nanoparticles is the reduction in toxicity
of the Zn ferrite as compared with other ferrites such as MnZn
ferrite [64]. Fig. 6. Effect of particle size on the magnetic coercivity [20].
Fig. 7. Nanoscale transition of magnetic nanoparticles from ferromagnetism to superparamagnetism [56].
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 907
Zinc ion has a strong effect on the magnetic properties of ferrites
and especially reduces the Curie temperature and for this reason it is
widely used as a common component in ferrites (Table 4). The zinc
ion can induce the self-controlled hyperthermia at relatively high
concentrations. The substitution of nonmagnetic ion such as Zn,
which has a preferential A site occupancy, results in the reduction of
the exchange interaction between A and B sites. Hence, by varying
the degree of zinc substitution, it is possible to vary magnetic
properties of the ne particles. The particle size and saturation
magnetization decrease with the increase in Zn concentration for
CoZn as well as for MnZn ferrites (Fig. 4 and Fig. 10) [65].
4.4. Synthesis method
Nanosize ferrites can be prepared by various synthesis techni-
ques. Due to the dramatic dependence of the magnetic properties on
the MNP morphology and structure, the preparative methods have
to allow a good control of the particle size, size distribution, shape
and crystal defects. The general strategy for preparing monodisperse
nanoparticles in solution phase is to separate the nucleation and
growth of nanocrystals. Summary comparison of various Iron oxide
magnetic nanoparticle synthesis methods is shown in Table 5 [66].
Fig. 12 illustrates the TEM micrographs of a Co-ferrite synthesized
by different methods. These images conrm the powder specica-
tions discussed in Table 5.
4.4.1. Co-precipitation
Co-precipitation method is a classical synthesis method used
to prepare uniform magnetic ferrite nanoparticles because of its
simplicity and productivity. The process involves separation of
the nucleation and growth of the nuclei via homogeneous
precipitation reactions [70]. It is widely used for biomedical
applications due to the ease of implementation and need for less
hazardous materials and procedures. In medicine co-precipitation
is specically the precipitation of an unbound antigen along with
Fig. 8. Central plane for a smaller nanosphere for K
S
/K
V
1 (a), 10 (b), 40 (c) and 60 (d). The Oz axis is vertical [58].
Fig. 9. Field-dependent magnetization measurements at RT of MFe
2
O
4
(MCo, Ni,
Mn) ferrites with particle diameter 7 nm.
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 908
an antigenantibody complex. The reaction principle for magne-
tite is simply as
Fe
2
2Fe
3
8OH

3Fe(OH)
2
2Fe(OH)
3
-Fe
3
O
4
4H
2
O
Fig .11 [71] shows the magnetizationtemperature curves of
MnZn ferrite prepared by (a) co-precipitation, (b) ceramic and
(c) co-precipitated and calcined methods. Magnetization of sam-
ple A is smaller than sample B. However, the value of sample C is
comparable to the one prepared by the ceramic method. The
difference could be associated to their higher particle sizes.
4.4.2. Microemulsions
The main advantage of emulsion methods is that the ferrite
particle size can be easily controlled by changing the size of
micelles and that the nano-reactors are isolated from each
other, limiting the particle growth. Micro-emulsion systems can
be divided into two categories water-in-oil (reverse micelle) and
oil-in-water (normal micelle). A microemulsion is a thermodyna-
mically stable isotropic dispersion of two immiscible liquids,
where the microdomain of either or both liquids is stabilized by
an interfacial lm of surfactant molecules [72]. Depending on
relative concentrations, surfactant molecules self-assemble into a
variety of structures in the solvent mixture, such as micelles,
bilayers or vesicles [73]. This dispersed phase provides a conned
environment for the synthesis and formation of nanoparticles
[7476]. Several kinds of surfactants have been applied for the
formation of such nano-reactors in which the nanoparticle
synthesis takes place, e.g. AOT [18], CTAB [77], SDS [78] and
polyethoxylates (Tween) [79].
4.4.3. Thermal decomposition
Different types of magnetic nanoparticles with control over
size and shape can be prepared by the thermal decomposition
method. This method has a suitable potential for large scale
production of high quality ferrite nanoparticles [80]. Monodis-
perse nanoparticles with good size control, narrow size distribu-
tion and good crystallinity of individual and dispersible magnetic
nanoparticles can essentially be synthesized through the thermal
decomposition of organometallic compounds in high-boiling
organic solvents containing stabilizing surfactants [70,81]. The
organometallic precursors include metal acetylacetonates,
[M(acac)
n
] (MFe, Mn, Co, Ni; n2 or 3, acacacetylacetonate),
metal cupferronates [M
x
Cup
x
] (Mmetal ion; CupN-nitroso-
phenylhydroxylamine, C
6
H
5
N(NO)O

) or carbonyls [82]. Oleic

acid, fatty acids, oleylamine and hexadecylamine are often used
as surfactants [83]. The precise control of morphology and size of
nanoparticles strongly depends on the reaction temperature, the
reaction time and the ratios of the starting reagents [84].
4.4.4. Solgel
The solgel technique is based on the hydrolysis of liquid
precursors and formation of colloidal sols. This method is per-
formed at low temperatures and can be used to synthesize pure,
Table 4
Magnetization, coercivity, Curie temperature, grain size and lattice parameter as a function of chemical composition [65].
Sample with estimated cations Magnetization measurement at 10 kOe Estimated Curie
temperature (1C)
Particle size
D
XRD
(nm)
Lattice
parameter (

A)
M
S
(emu/g) M
r
(emu/g) H
c
(Oe)
Co
0:901
Zn
0:102
Fe
1:96
O
4
54.1 10.6 223 415 11.1 8.390
Co
0:81
Zn
0:204
Fe
1:98
O
4
50.7 4.84 76.2 373 10.9 8.387
Co
0:70
Zn
0:31
Fe
1:96
O
4
48.8 2.35 33.5 352 9.8 8.385
Co
0:61
Zn
0:41
Fe
1:96
O
4
42.8 0.798 11.6 285 9.0 8.383
Co
0:51
Zn
0:5
Fe
1:95
O
4
39.6 0.499 9.77 267 8.8 8.356
Mn
0:875
Zn
0:099
Fe
1:94
O
4
42.4 1.99 12.8 360 11.3 8.442
Mn
0:789
Zn
0:21
Fe
1:96
O
4
48.1 1.45 9.02 10.8 8.440
Mn
0:699
Zn
0:295
Fe
1:98
O
4
44.8 1.27 8.66 303 10.1 8.439
Mn
0:591
Zn
0:399
Fe
1:96
O
4
35.1 0.717 8.58 196 9.2 8.436
Mn
0:499
Zn
0:495
Fe
1:99
O
4
33.5 0.459 8.7 165 8.5 8.409
Fig. 10. Variation of particle size with Zn substitution at room temperature [65].
Fig. 11. Magnetizationtemperature curves of MnZn ferrite prepared by
(a) co-precipitation, (b) ceramic and (c) co-precipitated and calcined methods [71].
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 909
stoichiometric, monodisperse and large size nanoparticles (tens to
hundreds of nanometers) with relatively narrow size distribution
in a large scale. The starting materials are metal precursors, metal
or metalloid element surrounded by various reactive ligands that
undergo slow hydrolysis and polycondensation reactions to form
a colloidal system named sol. The sol evolves and leads to the
formation of a network containing a liquid phase, called gel [85].
4.4.5. Hydrothermal
The hydrothermal or solvothermal method, a solution-phase
chemical method, was one of the most promising routes due to its
low cost and potential advantage for large-scale production of
ferrites. This method is based on a general phase transfer and
separation mechanism occurring at the interfaces of the liquid,
solid and solution phases present during the synthesis in aqueous
or organic systems at high temperature and pressure [86]. The
control of nanoparticle formation, size and distribution can be
achieved by choosing the appropriate mixture of solvents and
varying parameters such as temperature, pressure and reaction
time [87].
Reduction under hydrothermal conditions is performed to pre-
pare monodisperse nanoparticles, using metal salts, ethylene glycol,
sodium acetate and polyethylene glycol. Typically, the reaction
mixture is stirred to form a clear solution, then sealed in a Teon-
lined stainless-steel autoclave, heated to and maintained at tem-
peratures as high as 200300 1C for several hours (72 h) [88].
5. Spinel ferrites
Nano-ferrites are good candidates for biomedical purposes
since they present a high magnetic moment, they are chemically
stable and their surfaces are very reactive to attach biological
molecules. Moreover, the presence of the divalent metallic ion
(usually a d-block metal) can improve the determination of the
in-vivo biodistribution of such nanoparticles in blood probes.
In spinels the unit cell is of face-centered cubic symmetry. The
unit cell is formed by 32 oxygen atoms and 24 cations. There are
64 tetrahedral and 32 octahedral possible positions for cations in
the unit cell. Only 8 tetrahedral and 16 octahedral positions are
occupied by the cations. They are named A and B-positions [20].
Based on the different cation occupancies on the mentioned
crystal positions, a wide range of magnetic properties can be
achieved. Fig. 3 illustrates mass magnetization, magnetic spin
structure and magnetic moment of MFe
2
O
4
with a high monodis-
persity (so8%), single crystallinity and the stoichiometric composi-
tion [39]. The MFe
2
O
4
nanoparticles (12-nm) were examined with a
superconducting quantum interference device (SQUID) magnet-
ometer. When an external eld is applied, the magnetic spins in
the octahedral sites (O
h
) are aligned in parallel with the direction of
the external magnetic eld, but those in the tetrahedral sites (T
d
) are
aligned in antiparallel [89]. As a result, the MnFe
2
O
4
particles have
the highest mass magnetization and magnetic susceptibility. The
magnetic susceptibility gradually decreased as M
2
changed from
Fe
2
to Co
2
to Ni
2
: magnetic spin magnitude changed from
approximately 4 m
B
to 3 m
B
to 2 m
B
Table 6.
5.1. Iron ferrite
Historically, the rst magnetic nanoparticle used in magnetic
uids was magnetite Fe
3
O
4
. The MNPs iron oxide such as
magnetite (Fe
3
O
4
) or maghemite (g-Fe
2
O
3
) with a diameter of
520 nm have attracted much attention [95]. Maghemite is the
ferrimagnetic cubic form of Fe (III) oxide and differs from the
inverse spinel structure of magnetite through vacancies on the
cation sublattice with a slightly lower saturation magnetization
[96]. However, both compositions possess similar lattice para-
meters at 8.396 and 8.346

A for magnetite and maghemite,
respectively. The Fe
3
O
4
MNPs, which are superparamagnetic, have
intensively been investigated [95]because of their non-toxicity,
inherent biocompatibility, their easy synthesis in the form of
stable aqueous magnetic uids and their parallel development as
contrast agents in magnetic resonance imaging [97], as heat
mediators in hyperthermia treatments, and as magnetic guidance
Table 6
Spinel type, chemical formula, saturation magnetization at RT, Curie point, magnetocrystalline anisotropy, compatibility, critical single domain size and superparamagnetic
size of different ferrites [20,38,9094].
Ferrite Spinel type Chemical formula M
S
(emu/g) T
C
(K) K
1
( 10
5
) (erg/cm
3
) Compatibility D
C
(nm) D
SP
(nm)
CoFe
2
O
4
Inversed spinel Fe
3
[Co
2
Fe
3
]O
4
2
8094 790 18, 30 Unbiocompatible 70 14
NiFe
2
O
4
Inversed spinel Fe
3
[Ni
2
Fe
3
]O
4
2
56 860870 0.68 Unbiocompatible 100 28
Fe
3
O
4
Inversed spinel Fe
3
[Fe
2
Fe
3
]O
4
2
90100 860 1.2 Biocompatible 128 25
MnFe
2
O
4
Mixed spinel Me
1d
2
Fe
d
3
[Me
d
2
Fe
2d
3
]O
4
2
80 550620 0.25 Unbiocompatible 128 25
Table 7
Magnetic properties of Zn
x
Fe
1x
O.Fe
2
O
3
[64,65].
Chemical formula Diameter (nm) M
S
(emu/g) w
0
(cgs/g)
FeOdFe
2
O
3
4.670.7 19.8 0.004
Zn
0.14
Fe
0.86
OdFe
2
O
3
4.570.8 26.8 0.010
Zn
0.26
Fe
0.74
OdFe
2
O
3
4.570.7 43.1 0.020
Zn
0.34
Fe
0.66
OdFe
2
O
3
4.970.7 54.1 0.025
Zn
0.76
Fe
0.24
OdFe
2
O
3
4.570.8 30.0 0.008
Table 5
Summary comparison of various magnetic nanoparticle synthesis methods [6769].
Synthetic method Synthesis Reaction temp.
[1C]
Reaction
period
Solvent Surface-capping agents Size
distribution
Shape
control
Yield
Co-precipitation Very simple, ambient
conditions
2090 Minutes Water Needed, added during or after
reaction
Relatively
narrow
Not good High/
scalable
Thermal
decomposition
Complicated, inert
atmosphere
100320 hoursdays Organic
compound
needed, added during reaction very narrow very good high/
scalable
Microemulsion Complicated, ambient
conditions
2050 Hours Organic
compound
Needed, added during reaction Relatively
narrow
Good Low
Hydrothermal
synthesis
Simple, high pressure 220 Hours-days Water-ethanol Needed, added during reaction Very narrow Very good Medium
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 910
in drug delivery applications [98]. The magnetic properties of
magnetite can be affected by different divalent dopants like Zn
ion. Table 7 shows the effect of zinc content on the magnetic
properties of magnetite. It is clear that as the zinc content
increases up to 0.34 the magnetic properties increases and then
decreases as a result of reduction in super-exchange strength
between two sub-lattices Fig. 12.
5.2. Cobalt ferrites
Cobalt ferrite with a large magnetic multiaxial anisotropy,
moderate saturation magnetization, high Curie temperature,
remarkable chemical stability and mechanical hardness is one of
the most signicant magnetic materials [99102]. Nanocrystal-
line cobalt ferrite has recently been reported as a hard magnetic
material due to its high coercivity (5400 Oe) as compared with
co-ferrite prepared via conventional powder sintering [21].
For the CoFe
2
O
4
nanoparticles synthesized by the co-precipitation
method, the H
C
can be above 4000 Oe, much larger than that of
the CoFe
2
O
4
nanoparticles fabricated by other methods [103]. In a
system where K is greater than zero, due to the presence of the six
easy directions along the cube edges, there is a greater probability
that the randomly aligned particles will have an easy direction
close to any direction in which a eld is applied [62]. Cobalt
ferrite nanoparticles are suitable for the isolation and purication
of genomic DNA and the separation of PCR (polymerase chain
reaction) ready DNA [104,105] and especially in hyperthermia
treatment [106,107]. By the addition of zinc in cobalt ferrite, a
self-controlled hyperthermia with a suitable heat generation can
be obtained. Fig. 13 shows that the magnetization gradually
increases with increasing Zn
2
concentration (x) and reaches to
a maxima for x0.1 and then gradually decreases to a minimum
for x1 [108]. Furthermore, Fig. 14 depicts the eld-dependent
magnetization measurements at RT of CoFe
2
O
4
ferrites with
different particle sizes [60]. This gure reveals that with the
decreasing particle size the superparamagnetic behavior increases
at room temperature.
5.3. Manganese ferrites
Nano-sized Mn and MnZn ferrites are found to be of great use
in medical applications especially for hyperthermia application
and as a potential candidate for the contrast agent in MR imaging
[109,110]. The most signicant characteristics of Mn and MnZn
Fig. 12. TEM images of the Co-ferrite nanoparticles synthesized by (a) coprecipitation, (b) microemulsion, (c) thermal decomposition, (d) solgel and (e) hydrothermal
[6769].
Fig. 13. Change in the specic magnetization and Curie temperature with the
degree of zinc substitution in Mn
(1x)
Zn
x
Fe
2
O
4
(x0.10.5) [108].
Fig. 14. Magnetic behavior of three CoFe
2
O
4
ferrite samples with different
particle sizes.
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 911
ferrites are their high permeability and low losses, as well as a
good stability of permeability with temperature and time
[111,112]. This ferrite can be produced by different methods such
as solgel, co-precipitation and hydrothermal [113] methods.
They have also been found to have a very high magnetization
and large relaxation owing to their large magnetic spin magni-
tude [114,115]. The MnZn ferrites are distinguished for their low
Curie temperatures, low remaining magnetization and low values
of the magnetic crystalline anisotropy constant. Like other
ferrites, zinc ion can also affect the intrinsic magnetic properties
including Curie temperature and magnetization of this type of
ferrite, which can make it suitable for hyperthermia treatment.
The changes in the specic magnetization and Curie temperature
with the degree of zinc substitution are given in Fig. 15 [108].
The decrease in Curie point can be related to the increase in inter-
atomic distance between magnetic sites. Also the initial increase
in magnetization is attributed to the higher difference between
magnetization of two sub-lattices and the following decrease is
ascribed by the weakening of super-exchange strength between
two sites [112].
5.4. Nickel ferrites
Among all spinel ferrites, Ni and NiZn ferrites are one of the
most useful materials due to its low cost, high electromagnetic
performance, moderate saturation magnetization, low coercivity
and good chemical stability. The above specications make
Ni-based ferrites a good potential for biomedicine applications
[21,101,116]. NiZn ferrite particles can be used as effective
heating mediators for the hyperthermia application in cancer
therapy [99]. The main reason for considering Ni-ferrite nano-
particles as a hyperthermia agent is that these are expected to
have urgently required magnetic properties for hyperthermia
such as soft magnetism and small magnetic properties degrada-
tion at high frequency [117].
Like other ferrites, Zn ion changes the structural and magnetic
properties of Ni-ferrite and makes it suitable for different biome-
dicine applications. Fig. 16 shows the lattice parameter as a
function of zinc concentration across the Ni
1x
Zn
x
Fe
2
O
4
solid
solution series for the nanoparticles and bulk material fabricated
from the nanoparticles [118]. Fig.17 depicts the magnetization
curves of Ni-ferrite and doped Ni-ferrite [119]. It should be
mentioned that among akin ferrites, NiFe
2
O
4
is special: under
size diminution, its particles, along with usual superparamagnet-
ism, show strong reduction of magnetization with respect to that
of the bulk ferrite. NiFe
2
O
4
nanoparticles in ferrouids show a
spin-glass-like surface layer [120,121].
6. Conclusions
At the nanometric scale, the size reduction leads to interesting
magnetic properties, such as superparamagnetism, enhanced
anisotropy and surface effects. This paper attempts to give a
suitable summary and literature survey on the ferrouids and
their applications in hyperthermia with a focus on the magnetic
properties and the synthesis method of spinel ferrites as magnetic
cores. In hyperthermia application the goal is the higher value of
magnetic heat generation by a stable uid in a lower exposure
time. Nano-ferrites are good candidates for hyperthermia pur-
poses since they present a moderate magnetic moment, chemical
stability and a high specic absorption rate (SAR). For example in
the Co-ferrite the SAR parameter is at the highest level compared
to the other mentioned ferrites in the biological application range
Fig. 15. Change in the specic magnetization and Curie temperature with the
degree of zinc substitution.
Fig. 16. Lattice parameter as a function of zinc concentration [118].
Fig. 17. Room temperature magnetization curve of (a) Ni
1.0
Fe
2
O
4
, (b) Ni
0.90
Zn
0.10
Fe
2
O
4
, (c)Ni
0.80
Zn
0.20
Fe
2
O
4
, (d) Ni
0.70
Zn
0.30
Fe
2
O
4
, (e) Ni
0.60
Zn
0.40
Fe
2
O
4
, (f) Ni
0.50
Zn
0.50
Fe
2
O
4
, (g) Ni
0.40
Zn
0.60
Fe
2
O
4
, (h) Ni
0.30
Zn
0.70
Fe
2
O
4
, (i) Ni
0.20
Zn
0.80
Fe
2
O
4
, (j) Ni
0.10
Zn
0.90
Fe
2
O
4
and (k) Zn
1.0
Fe
2
O
4
[119].
I. Shari et al. / Journal of Magnetism and Magnetic Materials 324 (2012) 903915 912
(5 kA/m, 300 kHz). So based on which heat generation mechanism
we want, a suitable selection of magnetic core, surfactant layer
and liquid type can inuence the cancer treatment.
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