Hipertermia_noutate_citit

Nano Res

1

Targeted inductive heating of nanomagnets by

combined AC and static magnetic field

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

Tsinghua University Press 2015

Just Accepted

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Nano Research DOI 10.1007/s12274-015-0730-1

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.

Targeted inductive heating of nanomagnets by

combined AC and static magnetic field

Ming Ma, Yu Zhang( ), Xuli Shen, Jun Xie, Yan Li, Ning Gu( )

Received: day month year

Revised: day month year

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

ABSTRACT

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.

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

Nano Research DOI (automatically inserted by the publisher)

Address correspondence to Yu Zhang, [email protected]; Ning Gu, [email protected]

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2 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. Djardin 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 and frequency 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 C

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

blackbrown mixture was cooled to room

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3 Nano Res.

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 M).

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 (404020): 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.


4 Nano Res.

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 37C

in a 5% CO2 atmosphere in Dulbeccos modified

Eagles 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 100L MZF-containing medium (1mg/mL MZF)

in 250-L 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 104 cells per well and incubated at 37C

for 24h. Then MTT assay was carried out to test the

cell viability. 20l 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 150L

of DMSO was added to solubilize the cells. The

resultant solutions were measured in a microplate

reader (TECAN, Infinite 200) at 590. 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 = 2 nm obtained using a

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.

(a)

(b)


5 Nano Res.

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 emug-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


6 Nano Res.

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

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.

-0.05 0.00 0.050

10

20

30

40

50

60

70

Ma

gn

eti

c f

ield

(m

T)

x (m) 0.016 0.020 0.0245

10

15

20

Mag

neti

c F

ield

(m

T)

Magnets distance (m)

x

y

x

y

(a) (b)

(c) (d)


7 Nano Res.

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

agrees with the experimental and theoretical results

on ferromagnetic 12.8nm FeCo nanoparticles

reported by Carrys 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

phantoms 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 35.1C 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

0 200 400 600 8000

5

10

15

20

25

30

K

Time(s)

MZF 2mg/mL

MZF 1.5mg/mL

MZF 1mg/mL

MZF 0.5mg/mL

(a)

0 200 400 600 8000

5

10

15

20

25

T

(K

)

Time (S)

0mT

5mT

7mT

9mT

15mT

(b)

0 5 10 15

50

100

150

SA

R (

W g

-1)

Statics Magnetic Field (mT)

(c)

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.


8 Nano Res.

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.

Visually, we obtain good fits to these temperature

distributions with the Gaussian ,

where T is the temperature at Line L0, T0, T1, x0 and

are constants. The parameter T1 is the height of the

curve's peak, x0 is the position of the center of the

peak, and (the standard deviation) controls the

width of the curve. For phantom A, B and C, T1 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

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

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

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

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 29.6C. 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 phantoms centerline Line L0 (the white dash dot line marked by the

arrow) from thermal imagery.

(a)

0 10 20 30 40 50

30

32

34

36

Line L0 (mm)

phantom A

phantom B

phantom C

gauss fit

Te

mp

era

ture

(oC

)

(b)

Line L0


9 Nano Res.

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. Its 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

0

20

40

60

80

100

120

Comb

ined M

F 2#

Ce

ll V

iab

ility

(%

)

Contr

olAM

F

Comb

ined M

F 1#

a

b

b

c

(a) (b)

(c) (d)

control #1 #2 AMF

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.


10 Nano Res.

Medical Science (No. BL2013029), and the Jiangsu

Provincial Technical Innovation Fund for Scientific

and Technological Enterprises (No. BC2013011).

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11 Nano Res.

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