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Nano Res
DOI 10.1007/s12274-015-0730-1
Targeted inductive heating of nanomagnets
combined AC and static magnetic field
by
Ming Ma, Yu Zhang( ), Xuli Shen, Jun Xie, Yan Li, Ning Gu( )
Nano Res., Just Accepted Manuscript • DOI 10.1007/s12274-015-0730-1
http://www.thenanoresearch.com on January 28, 2015
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TABLE OF CONTENTS (TOC)
Targeted
inductive
heating of nanomagnets
by combined AC and
static magnetic field
Ming Ma, Yu Zhang*,
Xuli Shen, Jun Xie, Yan
Li, Ning Gu*
Southeast
University,
China
.
Combined AC and static magnetic field was used to restrict the hyperthermia heating area
and reduce the side effect in the magnetic field inductive hyperthermia of
nanomagnets.
Nano Research
DOI (automatically inserted by the publisher)
Review Article/Research Article Please choose one
Targeted inductive heating of nanomagnets
combined AC and static magnetic field
by
Ming Ma, Yu Zhang( ), Xuli Shen, Jun Xie, Yan Li, Ning Gu( )
Received: day month year
ABSTRACT
Revised: day month year
The conversion of electromagnetic energy into heat by nanomagnets has the
potential to be a powerful, non-invasive technique for cancer therapy by
hyperthermia and hyperthermia-based drug release, while temperature
controllability and targeted heating are the challenges to intensive application
of such magnetic inductive hyperthermia. This study was designed to control
the hyperthermia position and area using combined alternating current (AC)
and static magnetic field. At first, MnZn ferrite (MZF) nanoparticles which
exhibited excellent hyperthermia properties were prepared and characterized
as inductive heating mediator. We built model static magnetic fields simply
using a pair of permanent magnets and studied the static magnetic field
distributions by measurements and numerical simulations. The influence of the
transverse static magnetic fields on hyperthermia properties was then
investigated on MZF magnetic fluid, gel phantoms and SMMC-7721 cells in
vitro. Results show static magnetic field can inhabit the temperature rising of
MZF nanoparticle in AC magnetic field. But in the uneven static magnetic field
formed by magnet pair with repellent poles face-to-face, heating area can be
restricted in central low static field; meanwhile the side effect of hyperthermia
can be reduced by surrounding high static field. It means we can position the
hyperthermia area, protect the non-therapeutic area, and reduce the side effects
just using well-designed combined AC and static field.
Accepted: day month year
(automatically inserted by
the publisher)
© Tsinghua University Press
and Springer-Verlag Berlin
Heidelberg 2014
KEYWORDS
Hyperthermia; magnetic
nanoparticles;
static
magnetic field; alternating
magnetic field; Mn-Zn
ferrite
1 Introduction
When magnetic nanoparticles (MNPs) are subject to
an alternating magnetic field, the dissipated
magnetic energy can be converted into thermal
energy to lead the particle be a heating source [1, 2].
The temperature enhancement of the magnetic
nanoparticles under the external alternating
magnetic field (AMF) has found applications in
many fields, such as thermosensitive polymers [3],
cancer therapy by hyperthermia [4], and
hyperthermia-based drug release [5]. Hyperthermia
is recognized as an alternative treatment that can be
delivered alone or as an adjunct to radiation and/or
chemotherapy to treat cancer [6]. So far,
hyperthermia has successfully been used in the
context of multimodality treatment schedules for
Address correspondence to Yu Zhang, [email protected]; Ning Gu, [email protected]
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Nano Res.
recurrent breast, head, and neck or skin malignancies.
MNPs-based hyperthermia treatment has a number
of
advantages
compared
to
conventional
hyperthermia
treatment.
Nontoxicity,
biocompatibility, high-level accumulation in the
target tumor and effective absorption of the energy of
AMF are the merits of MNPs-based hyperthermia.
Temperature controllability and targeted heating are
all the challenges to the MNPs-based hyperthermia
and magnetically modulated controlled drug delivery.
The targeted treatments can be made possible if the
magnetically induced hyperthermia is combined
with MRI-based location or magnetic targeting of
tumors which both need to use static magnetic field
[7, 8]. The power generated by the MNPs is evaluated
by the specific losses or, more commonly used, by
their specific absorption rate (SAR), which may vary
by orders of magnitude in dependence on structural
and magnetic properties on the one hand, and
amplitude and frequency of the external alternating
magnetic field, on the other. But a few theoretical and
experimental works have pointed out that the
presence of a static magnetic field could influence on
the magnetic hyperthermia properties or SAR of
MNPs [9-11]. According to the theoretical studies
reported by P. Déjardin et al. [11], for
superparamagnetic particles, the static field changes
substantially the nonlinear magnetization dynamics,
primarily the behavior of the reversal time of the
magnetization τ and frequency ω max, where the
imaginary part of the complex susceptibility reaches
a maximum; for anisotropic single-domain particles,
a bias static field of a small value can strongly affect
the shape of the dynamics magnetic hysteresis loop.
This result implies that using weak changes of the
static bias field magnitude one may effectively
control the heat production (SAR) in a magnetic
nanosystem working as a hyperthermia source. It
seems the result is pessimistic on the pursuit of
enhanced emagnetic hyperthermia property of MNPs.
But it also raises a possibility that we can position the
therapeutic area and control treatment temperature
by regulating the strength of combined static
magnetic fields of the therapeutic area in a magnetic
hyperthermia nanosystem. Moreover, we can use a
well-designed static magnetic field to protect the
non-therapeutic area and reduce the side effects on
the normal tissue.
In the present paper, we prepared MnZn ferrite (MZF)
nanoparticles
which
exhibited
excellent
hyperthermia properties in alternating current (AC)
magnetic field. We built two model static magnetic
fields simply using a pair of permanent magnets:
near-uniform transverse static magnetic field in the
central area of magnet pair with two attractive poles
face-to-face; uneven static magnetic field of magnet
pair with two repellent poles face-to-face, where
magnetic field intensity is near zero in the central
point between two magnet poles and the surround
gradually increases. We studied the two static
magnetic field distributions by measurements and
numerical simulations. The influence of the
transverse static magnetic field on magnetic
hyperthermia properties was then investigated by
temperature measurements of MZF magnetic fluid
and gel phantoms. To achieve the aims of controlling
hyperthermia region and eliminating side effect, we
superposed the above mentioned uneven static
magnetic field to the AC magnetic field induced
hyperthermia area of MZF gel phantoms and cell
suspensions. The temperatures and cell killing effect
of cell suspensions at different regions were
measured and compared. We show, magnetic
hyperthermia by combined AC and static magnetic
field can be a new choice to the targeted regional
hyperthermia treatment system while we have an
excellent magnetic nanoparticle as heating mediator.
2 Experimental section
2.1 Synthesis of hydrophobic MnZn ferrite
nanoparticles.
The synthesis was carried out under an oxygen free
atmosphere in a 50ml three-neck round bottom flask.
MnCl2 (30 mM), ZnCl2 (20 mM), oleic acid (0.3 M),
oleylamine (0.3 M) and octadecene (20 ml) were
mixed and stirred under the flow of nitrogen at room
temperature. The mixture was then heated to 110 ºC
under nitrogen atmosphere and maintained at this
temperature for 1 h to remove the water and HCl in
solution. Then 2mmol Fe(acac) 3 was added as
precursor and heated to 200 °C for 30min. The
reaction temperature was then increased to a reflux
temperature(~290 °C) at different heating rate (3.3 °C
/min, 6.6 °C /min and 10 °C /min) and the reflux
continues for 30min during which the colour of the
solution slowly turns from brown to black. The
black–brown mixture was cooled to room
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temperature and then precipitated with 40 mL of
ethanol; it was then separated using a magnet. The
solvent and nonmagnetic suspension were decanted,
and the precipitate was washed once with acetone,
and separated again by centrifugation to remove
excess surfactants. Finally the product was dispersed
in hexane.
2.2 Hydropholic MnZn ferrite nanoparticles.
A hexane dispersion of hydrophobic MZF
nanoparticles (about 50 mg in 10 mL) was added to a
suspension of DMSA (about 25 mg in 10mL) in
acetone. The mixture was shaken at 60 °C for 4 h. The
product was precipitated then washed twice with
ethanol carefully and dispersed in deionized water
(18 MΩ).
2.3 Nanoparticle Characterization.
Particles were imaged using a transmission electron
microscopy (TEM, JEM-200CX, 200 kV). X-ray
powder diffraction patterns of the particle assemblies
were collected on a Rigaku D/Max-RA diffractometer
under Cu KR radiation. The elemental analysis was
carried out using energy dispersive X-ray
spectroscopy (EDS) analyzer connected with the
scanning electron microscope (SEM). Magnetic
studies were carried out using a Lakeshore 7404
vibrating sample magnetometer (VSM).
2.4 Inductive heating of MZF magnetic fluid in AC
magnetic field.
Inductive heating was accomplished by positioning
the MZF magnetic fluid (DMSA-modified MZF
nanoparticles dispersed in aqueous with different
MZF concentrations) sample in an alternating
magnetic field (50kHz, 34kA/m). The equipment
consisted of a high-frequency generator, a
water-cooled inductive coil with a diameter of 3 cm
with 3 loops. An optical fiber thermometer was used
for temperature measurement.
The specific absorption rate (SAR) was deduced from
the initial linear rise in temperature (plain line)
versus time, dT/dt, normalized to the mass of
magnetic material and the heat capacity of the
sample, which can be expressed as
where C is the volumetric specific heat capacity of
the sample, Vs is the sample volume, and m is the
mass of magnetic material in the sample.
2.5 Numerical simulations and measurements of the
static magnetic fields.
Finite element methods were used to solve the
magneto-static problem numerically. We computed
the static magnetic fields from pair of permanent
magnets in the 2D axial symmetry space dimension
using the AC/DC module of the COMSOL
Multiphysics software (Version 3.5a, COMSOL Inc.,
Burlington, MA). The numerical model applied in the
simulations is described in detail in elsewhere[12].
COMSOL computes the magnetic field B and its
components in a region of interest, which can be
exported from the program.
Corresponding to the simulations, we built two static
magnetic fields simply using a pair of NdFeB
permanent magnets (40 ×40×20): attractive poles
face-to-face or repellent poles face-to-face. The
static magnetic field intensities were measured by a
teslameter.
2.6 Inductive heating of MZF magnetic fluid in
combined AC and static magnetic field.
Combined AC and static
magnetic field were
constructed with two NdFeB permanent magnets
placed symmetrically on both side of the inductive
coil with attractive poles face-to-face (Fig. 1(a)). The
static magnetic field intensity in the centre of the coil
was changed by changing the distance between two
permanent
magnets.
MZF
magnetic
fluid
concentration is 1.5 mg/mL. The alternating magnetic
field is 50kHz, 34kA/m. The temperature of MZF
magnetic fluid was monitored during the process of
magnetic field irradiation.
2.7 Heat generation of MZF-doped gel phantoms.
Agarose solution (1%) was mixed with the MZF at
concentration of 1mg/mL. MZF-agarose solution was
then drawn and hardened in a 1-mL syringe tube.
The tube filled with MZF-agarose gel was placed
inside the coil (Fig. 1(b)). Two NdFeB permanent
magnets placed symmetrically on both sides of upper
and lower of the coil in distance of 140mm.
Temperature of the gel phantom was measured by a
portable precision infrared radiation thermometer
(Fluke, Ti32 ) 10 min after the phantom was placed in
the combined AC and static magnetic field. The static
magnetic field intensities in point A, B and C (Figure
1B right) were measured.
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(a)
(b)
Figure 1. Schematic of the experimental setup of combined AC and static magnetic field for heating MZF magnetic fluid (a)
and MZF gel phantom(b). All testing samples were placed inside an inductive coil which was connected to an AC magnetic
field generator and cooled by running water. A pair of NdFeB permanent magnets placed two sides of the inductive coil
face-to-face to form the static magnetic field.
2.8 Cell culture and hyperthermia in vitro.
The cell line SMMC-7721(a human liver carcinoma
cell line) was used. The cells were maintained at 37ºC
in a 5% CO2 atmosphere in Dulbecco’s modified
Eagle’s medium (Gibco) supplemented with 10% fetal
bovine serum.
The cells were washed with PBS under gentle
shaking and detached by trypsin treatment. MZF
nanoparticles were sterilized by filtration. The cells (1
×108) were collected as cell pellets and suspended
with 100μL MZF-containing medium (1mg/mL MZF)
in 250-μL micro tubes. The micro tubes with cell
suspensions were placed in the coil for magnet
irradiation. After magnetic irradiation for 40min, the
MZF-containing medium was carefully removed by
centrifugation. The cells were re-suspended in fresh
medium and seeded into 96-well plate (Corning
Glass) with 10 4 cells per well and incubated at 37°C
for 24h. Then MTT assay was carried out to test the
cell viability. 20μl of MTT-solution (5 mg MTT/mL
phosphate-buffered saline) (Sigma), was then added
to each well, followed by 4 hours incubation in
darkness. The test solution was decanted, and 150μL
of DMSO was added to solubilize the cells. The
resultant solutions were measured in a microplate
reader (TECAN, Infinite 200) at λ590. Cell viability
was determined by the formula: cell viability (%) =
(absorbance of the treated wells - absorbance of the
blank control wells) / (absorbance of the negative
control wells - absorbance of the blank control wells)
× 100%. The negative control cells were not exposed
to the magnetic field. Experiments were performed in
triplicates. Further details on the MTT-test are
provided in a previous study [13] .
3 Results and discussion
3.1 Characterization of nanoparticles.
Monodisperse MnZn ferrite (MZF) nanoparticles
were prepared by the well-known thermal
decomposition method. To date, the thermal
decomposition method is very promising technique
to fabricate high-quality superparamagnetic and
monodisperse iron oxide nanoparticles [14]. Typically,
this method involves decomposition of Fe(acac) 3 in a
high-boiling solvent in the presence of surfactants
such as oleic acid and oleylamine. The morphology
of the prepared MnZn ferrite nanoparticles is shown
by the TEM image in Fig. 2(a). Nanoparticles are
roughly spherical shapes mostly, and a few parts are
octahedral shapes. Figure 2(b) shows the
nanoparticles size distribution, where the average
diameter is 17nm with σ = 2 nm obtained using a
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Gaussian fit. Figure 2(c) shows the typical XRD
pattern of prepared MZF nanoparticles. As shown in
the figure, the position and the relative intensity was
matched well to the series of Bragg reflections
corresponding to the spinel structure.
EDS was used to determine the chemical composition
of the obtained MnZn ferrite nanoparticles. The
result from EDS spectra shows that the nanoparticles
contain Fe, O, Mn and Zn, and no contamination
element is detected. The atomic ratio of Fe:Mn:Zn is
about 17.8:1.1:1.0, indicating that the chemical
formula of the as-synthesized MnZn ferrite is
unstoichiometric in nature. The chemical formula of
the MZF is determined to be Mn0.17Zn0.15Fe2.68O4
according this measured atomic ratio.
The magnetic properties were measured by the VSM
at room temperature as shown in Fig. 2(d). The
saturation magnetization value Ms of the as-prepared
MZF nanoparticles is 102.5 emu·g-1, and the
coercivity value Hc for the samples is 91 Oe. It is well
known that the saturation magnetization of bulk
Fe3O4 is about 85 - 100 emu/g [15]. In present study,
the saturation magnetization of the MZF
nanoparticles is larger than that of bulk Fe3O4. We
propose that the off-stoichiometric chemical
composition of MnZn ferrite particles may further
lead to a change of the structure of as-prepared
particles to mixed spinel type. The rich Fe3+ in our
samples (the molar ratio of Fe/Zn is about 17.9,
Fe/Mn is 15.8) may result in more Fe3+ ions in the B
site, making the materials more ferrimagnetic and of
higher saturation magnetization [16]. Here the B sites
are occupied by Mn2+xFe3+1.32-xFe2+0.68(0<x<0.17) and the
A sites are occupied by Mn2+0.17-xZn2+0.15 Fe3+0.68+x. When
an external magnetic field was applied to this
structure, the magnetic spins in B sites aligned in
parallel with the direction of the external magnetic
field, but those in the A sites aligned antiparallel.
Therefore, prepared MZF had highest magnetic
susceptibility, with approximate magnetic spin
moment of 5.07μB, higher than 4.0μB of bulk Fe3O4
[17].
3.2 Numerical simulations and measurements of the
static magnetic fields.
The model static magnetic fields were formed simply
by a pair of permanent NdFeB magnets. We studied
the static magnetic field distributions by 2-D
numerical simulations and measurements. Figure 3(a)
and (b) show the two different simulated static
magnetic fields from a pair of 2-D rectangle
permanent magnets (20mm×40mm) placed with two
attractive poles (Fig. 3(a)) and two repellent poles
(Fig. 3(b)) face-to-face at a distance of 16 cm on the
center simulation region. The remnant magnetization
of the magnet (NdFeB) is 0.2 T. The point directly
centered between the magnets is taken as the
coordinate center. Figure 3(c) shows the computed
and measured data of magnetic fields along the x
(a)
25
%
20
(b)
15
10
5
0
12
(c)
311
400
222
100
14
16
18
20
Diameters (nm)
22
(d)
M(emu/g)
50
440
220
511
0
-50
-100
20
30
40
50
60
2(degree)
70
80
-6000 -4000 -2000
0
H(Oe)
2000
4000
6000
Figure 2. TEM image (a), size distribution (b), XRD pattern (c) and hysteresis loop (d) of the prepared MZF
nanoparticles.
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axis, the axis of symmetry between the two magnets.
Figure 3(d) compares the measured and computed
data of the static magnetic fields at the point centered
between the magnets with different magnets distance.
The numerical calculations show excellent agreement
with the experimental measurements. We make
several observations: For two symmetrical mutual
repellent poles face-to-face, the field is zero in the
center between the magnets (as is to be expected
from symmetry considerations), maximal at the
magnets’ surface, and then decays approximately
exponentially with increasing distance from the
magnets’ surface. For two attractive poles face-to-face,
likewise, the field is minimal at the center between
the magnets and maximal at the magnets’ surface,
there is a region in the center between two poles
where the magnetic field is parallel and near uniform.
And the magnetic field at the center decreases
rapidly with increasing distance between the magnet
pair.
3.3 Heat generation of MZF magnetic fluid in
combined AC and static magnetic field.
Figure 4(a) displays typical experiments showing the
evolution of temperature as a function of time T(t) for
MZF magnetic fluid with different concentrations in
AC magnetic field of 50kHz, 34kA/m. However, the
estimated values of SAR were determined to be
essentially independent of the amount of MZF. The
temperature increase with time for MZF magnetic
fluid (concentration of 1.5mg/mL) after application of
(a)
(b)
y
y
x
x
70
(d)
20
Magnetic Field (mT)
Magnetic field (mT)
(c) 60
50
40
30
20
10
0
-0.05
x0.00
(m)
0.05
15
10
5
0.016
0.020
Magnets distance (m)
0.024
Figure 3. Finite element simulations of magnetic field of magnets with two attractive poles (a) and two repellent poles (b)
face-to-face. Numerical 2-dimensional calculations were carried out in COMSOL. The graphs show color-coded iso-contour of the
magnetic flux density (unit: mT). The local direction of the magnetic field B is indicated by the cyan arrows. (d) Magnetic fields as a
function of distance from the center of magnet pair along the x axis ( y = 0 ). Solid black line shows the results of calculations of
magnets with two attractive poles while blue dashed line shows the calculation results of magnets with two repellent poles. Scattered
data points (black square and blue triangle) are from measurements of the two magnetic fields with a Teslameter. (d)Central static
magnetic fields (x = 0, y = 0) as a function of distance of attractive magnet pair. Solid black line and scattered data points (blue
square) are from calculations and measurements respectively.
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combined AC and static magnetic field schematized
in Fig. 1(a) is shown in Fig 4(b). The static magnetic
field was formed by a pair of NdFeB permanent
magnets placed two sides of the inductive coil of AC
magnetic field with attractive poles face-to-face. As
shown in Fig. 3(d), the static magnetic field intensity
in the coil was near-uniform which was adjusted by
change the distance between the two magnets. SAR
values as a function of static magnetic field intensity
are summarized in Fig. 4(c). They display a sharp
decrease of SAR as increasing the static magnetic
field. A small static magnetic field of 5mT is enough
to significantly inhabit the SAR value. The result
(a) 30
MZF
MZF
MZF
MZF
25
K
20
2mg/mL
1.5mg/mL
1mg/mL
0.5mg/mL
15
10
5
0
0
200
400
600
Time(s)
800
25
(b)
0mT
5mT
7mT
9mT
15mT
20
T (K)
15
10
5
0
0
200
400
600
Time (S)
800
-1
SAR (W g )
(c)150
100
50
0
5
10
Statics Magnetic Field (mT)
15
Figure 4. Heat generation of MZF magnetic fluid on
combined AC and static magnetic field. (a) Temperature vs
time curves of MZF magnetic fluid on different static
magnetic field; (b)Decrease of SAR value with static
magnetic field. MZF magnetic fluid concentration is 1mg/mL.
The AC magnetic field is 50kHz, 34kA/m.
agrees with the experimental and theoretical results
on ferromagnetic 12.8nm FeCo nanoparticles
reported by Carry’s group[18]. They measured the
high-frequency hysteresis loops when an alternating
field and a transverse static magnetic field were
applied together. Their measurement results show
that a small static magnetic field can significantly
reduce the hysteresis loop area, its squareness and
the overall susceptibility of the sample. This result
implies that using weak changes of the static bias
field magnitude one may effectively control the heat
production in a magnetic nanosystem working as a
hyperthermia source.
3.4 Heat generation of MZF gel phantom.
MZF nanoparticles-doped agarose gel phantom was
used here to simulate human or animal tissue. The
thermograms of MZF gel phantoms heated with
magnetic field are presented in Fig. 5(a). Figure 5(b)
shows the temperature data collected along the
phantom’s centerline (Line L0) from thermal imagery.
The central section of the phantom placed inside the
coil was heated above 33.6 °C and the maximum
temperature reached 35.1ºC after 10min of irradiation
on the AC magnetic field (phantom A, Fig. 5(a)). Two
ends of the phantom outside the coil were heated at
least 1.0 °C above the background temperature by the
attenuated edge AC magnetic field. Phantom C (Fig.
5(a)) was irradiated in combined AC and static
magnetic field of magnets with two attractive poles
face-to-face. The static magnetic field magnitude at
point A, B and C (see Fig. 5(a)) was measured as
19.6mT, 22.5mT and 35.5mT respectively. The
maximum temperature of phantom C was 33.3 °C,
1.8 °C lower than phantom A. The edge temperature
of phantom C was same with the background
temperature. Obviously, the static magnetic field
constrains the temperature rising of MZF gel
phantom on AC magnetic field. Phantom B was
irradiated in combined AC and static magnetic field
of magnets with two repellent poles face-to-face.
Different with attractive poles face-to-face, the static
magnetic field at point A, B and C (see Fig. 1(b)) was
measure as 0.1mT, 8.4mT and 27.1mT respectively.
The maximum temperature of phantom B was
34.7 °C, only 0.4 °C lower than phantom A, 1.4 °C
higher than phantom C. The edge temperature of
phantom B was 30.0 °C, only 0.4 °C higher than
background temperature. The low field in the central
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region of the static magnetic field constructed with
two repellent poles face-to-face cannot constrain the
central temperature rising of MZF gel phantom
effectively. But, surround high field can constrain the
edge temperature rising, which can be clearly seen by
comparing phantom A and B.
hyperthermia with the combined AC and static
magnetic field.
3.5 Hyperthermia in vitro with SMMC-7721 cell.
Heat generation in tumor cells SMMC-7721 was then
studied. Two micro tubes with MZF magnetic
nanoparticles and SMMC-7721 cell suspensions were
36
(a)
phantom A
phantom B
phantom C
gauss fit
34
o
Temperature ( C)
(b)
32
30
0
10
20
30
Line L0 (mm)
40
50
Line L0
Figure 5. (a)The thermographics images of MZF gel phantoms taken 10 min after heated on an AC magnetic field (phantom A),
combined AC magnetic field and static field of magnets with two repellent poles (phantom B) and two attractive poles face-to-face
(phantom C). The background temperature is 29.6º
C. The length of the bar is 10mm. The box marks the section of the phantom
placed inside the coil. (b) Temperature data collected along the phantom’s centerline Line L 0 (the white dash dot line marked by the
arrow) from thermal imagery.
Visually, we obtain good fits to these temperature
distributions with the Gaussian
,
where T is the temperature at Line L0, T 0, T 1, x0 and σ
are constants. The parameter T 1 is the height of the
curve's peak, x0 is the position of the center of the
peak, and σ (the standard deviation) controls the
width of the curve. For phantom A, B and C, T 1 is
4.85, 4.57 and 4.20 respectively, implying temperature
difference between center and edge of MZF magnetic
phantom in the three magnetic fields. The parameter
σ is related to the full width at half maximum
(FWHM) of the peak according to
.[19]
Here, FWHM is 32.0, 24.3 and 32.8mm respectively
for phantom A, B and C. Obviously, phantom A and
C have similar FWHM. Only the FWHM of phantom
B is significantly less than that of the other two
phantoms, and closed to the width of heating region
of the coil (20mm). It means that we can control of
therapeutic area and reduce of side effect of
placed in the inductive coil according to the
arrangement shown in Fig. 6(a). A pair of permanent
magnets was placed two sides of the coil to form the
static magnetic field. The thermographics images of
SMMC-7721 cell suspension in micro tubes after
magnetic field irradiation are shown in Fig. 6(c) and
(d). The temperature of the cell suspension
incorporating MZF magnetic nanoparticles was
raised from 33.7 °C (control, Fig. 6(c)) to 44.0 °C
(AMF, Fig. 6(c)) after 40min of AC magnetic
field(AMF) irradiation (without static magnetic field)
and kept constant. These conditions seemed to be
sufficient for hyperthermia, as shown by the study of
the cell killing effect (Fig. 6(b)). Indeed, when an AC
magnetic field was applied to SMMC-7721 cells
incorporating MZF magnetic nanoparticles, the cell
viability decreased quickly to 61.5%. Then we
applied the combined AC and static magnetic field
arranged as Fig. 6(c) to heat the cells. Obviously, the
two cell suspensions placed at #1 and #2 separately
had distinctive different temperature rising in the
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9
Nano Res.
a
120
c
100
Cell Viability (%)
(b)
(a)
b
80
b
60
40
20
0
n
Co
(c)
tr o
l
AM
#
#
F
ine
mb
Co
dM
F1
dM
Co
m
F2
e
bin
(d)
control
AMF
#1
#2
Figure 6. (a)Schematic of the experimental setup of combined AC and static magnetic field for heating cell suspensions. (b)
MTT assay values for SMMC-7721 treated on AC magnetic field (AMF) and combined AC and static magnetic fie ld (combined
MF #1 and #2 correspond to the tubes of cells which were placed at #1 and #2 inside the coil, respectively). Different letters
means statistically significant differences at p < 0.05. (c), (d) The thermographics images of SMMC-7721 cell suspension in
micro tubes. Control: the cell suspension was not irradiated by magnetic field. AMF: the cell suspension was irradiated by AC
magnetic field for 40min. #1 and #2: the tubes of cells which were placed at #1 and #2 inside the coil and irradiated by the
combined AC and static magnetic field for 40min.
applied combined AC and static magnetic field. The
temperature of cell suspension at #2 reached
44.3 °C(#2, Fig. 6(d)) after 40min of magnetic
irradiation, identically to that irradiated by the AC
magnetic field. However, the temperature of cell
suspension at #1 reached 42.0 °C(#1, Fig. 6(d)), 2.3 °C
lower than #2, though the distance between #1 and #2
was only 15mm. Accordingly, the cell viability at #2
was 53.6%, whereas the cell viability at #1 was 75.4%,
there were statistically significant differences (p <
0.05). The results in vitro show the magnetic
inductive hyperthermia can be located at a
designated very small region just by applying a
well-designed static magnetic field.
4 Conclusion
We investigated the inductive heating properties of
prepared MnZn ferrite nanoparticle in combined AC
and static magnetic field. The model static magnetic
fields applied here were formed simply by a pair of
NdFeB magnets. It’s found the static magnetic field
can inhabit the inductive temperature rising of
nanomagnets in AC magnetic field. But, on the
hyperthermia experiments of gel phantom and
cancer cells in vitro, we took advantage of the results
to control the hyperthermia heating area and position
successfully using an uneven model static magnetic
field formed by magnet pair with repellent poles
face-to-face. The results imply magnetic inductive
hyperthermia using combined AC and static
magnetic field may be a feasible method to optimize
and control a hyperthermia treatment with the
objective to enhance treatment quality and
documentation.
Acknowledgements
This research was supported by the National
Important Science Research Program of China (No.
2011CB933503, 2013CB733800), the National Natural
Science Foundation of China (No. 31170959,
61127002), the Jiangsu Provincial Special Program of
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Research
10
Nano Res.
Medical Science (No. BL2013029), and the Jiangsu
Provincial Technical Innovation Fund for Scientific
and Technological Enterprises (No. BC2013011).
Zahn,
M.
Heating
in
the
mri environment
due
to
superparamagnetic fluid suspensions in a rotating magneticfield.
Journal of Magnetism and Magnetic Materials 2010, 322,
727–733.
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