Effects of Mn concentration on the ac magnetically induced heating characteristicsof superparamagnetic Mn x Zn 1 x Fe 2 O 4 nanoparticles for hyperthermiaMinhong Jeun, Seung Je Moon, Hiroki Kobayashi, Hye Young Shin, Asahi Tomitaka, Yu Jeong Kim, Yasushi

Takemura, Sun Ha Paek, Ki Ho Park, Kyung-Won Chung, and Seongtae Bae

Citation: Applied Physics Letters 96, 202511 (2010); doi: 10.1063/1.3430043 View online: http://dx.doi.org/10.1063/1.3430043 View Table of Contents: http://scitation.aip.org/content/aip/journal/apl/96/20?ver=pdfcov Published by the AIP Publishing Articles you may be interested in Origin of ferromagnetism in self-assembled Ga 1 x Mn x As quantum dots grown on Si Appl. Phys. Lett. 97, 242505 (2010); 10.1063/1.3526378 Static and dynamic magnetic behavior of nanocrystalline and nanocomposites of ( Mn 0.6 Zn 0.4 Fe 2 O 4 ) (1 z ) ( SiO 2 ) z ( z = 0.0 , 0.10 , 0.15 , 0.25 ) J. Appl. Phys. 108, 093912 (2010); 10.1063/1.3499644 Magnetic resonance in Fe x Mn 1 x S single crystals J. Appl. Phys. 106, 073909 (2009); 10.1063/1.3234402 Functionalization-induced improvement in magnetic properties of Fe 3 O 4 nanoparticles for biomedicalapplications J. Appl. Phys. 105, 07B317 (2009); 10.1063/1.3073654 Fabrication of magnetic porous hollow silica drug carriers using Ca C O 3 Fe 3 O 4 composite nanoparticlesand cationic surfactant double templates J. Appl. Phys. 103, 07A320 (2008); 10.1063/1.2837490

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Effects of Mn concentration on the ac magnetically induced heatingcharacteristics of superparamagnetic MnxZn1−xFe2O4 nanoparticlesfor hyperthermia

Minhong Jeun,1 Seung Je Moon,1 Hiroki Kobayashi,2 Hye Young Shin,3 Asahi Tomitaka,2

Yu Jeong Kim,4 Yasushi Takemura,2 Sun Ha Paek,3 Ki Ho Park,4 Kyung-Won Chung,5

and Seongtae Bae1,a�

1Department of Electrical and Computer Engineering, Biomagnetics Laboratory (BML),National University of Singapore, Singapore 1175762Department of Electrical and Computer Engineering, Yokohama National University,Yokohama 240-8501, Japan3Department of Neurosurgery, Cancer Research Institute, Ischemic/Hypoxic Disease Institute, SeoulNational University College of Medicine, Seoul 110-744, Republic of Korea4Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-744,Republic of Korea5Daion Co. Ltd., Incheon 405-846, Republic of Korea

�Received 8 February 2010; accepted 25 April 2010; published online 21 May 2010�

The effects of Mn2+ cation concentration on the ac magnetically induced heating characteristics andthe magnetic properties of superparamagnetic MnxZn1−xFe2O4 nanoparticles �SPNPs� wereinvestigated to explore the biotechnical feasibility as a hyperthermia agent. Among theMnxZn1−xFe2O4 SPNPs, the Mn0.5Zn0.5Fe2O4 SPNP showed the highest ac magnetically inducedheating temperature ��Tac,mag�, the highest specific absorption rate �SAR�, and the highestbiocompatibility. The higher out of phase susceptibility ��m� � value and the higher chemical stabilitysystematically controlled by the replacement of Zn2+ cations by the Mn2+ cations on the A-site�tetrahedral site� are the primary physical reason for the promising biotechnical properties ofMn0.5Zn0.5Fe2O4 SPNP. © 2010 American Institute of Physics. �doi:10.1063/1.3430043�

Magnetic hyperthermia �MH� using a superparamagnticenanoparticle agent �SPNA� has recently drawn huge attrac-tion due to its clinical promises.1,2 Accordingly, the intereststo utilize the ternary phase of SPNPs, MFe2O4 �M=Fe, Co,Ni, and Mg�, with a mean diameter below 10 nm for a MHagent has increased dramatically. However, despite theirpromising chemical, physiological, biotechnical, and physi-cal properties suitable for SPNA applications,3 an insufficient�Tac,mag and low specific absorption rate �SAR� at the physi-ologically tolerable range of frequencies and magnetic fields�fappl�100 kHz, Happl�200 Oe� are still revealed as thetechnical challenges to be overcome for a real clinical MH.4,5

Thus, a great deal of research activity is being conducted inorder to develop a functional SPNA and to improve the effi-ciency of currently used ferrite SPNAs. The quarterly phaseof bulk MnxZn1−xFe2O4, which is one of the softest �orthe highest permeability� ferrite materials, is consideredto be a potential material for MH agent. The main physicalreason is that it has a good electrical field absorptionand a large power loss �500–200 W /m3� at a low frequency��100 kHz� which is due to its low electrical resistivity�0.02–20 � m�.6,7 Furthermore, its magnetic properties, i.e.,saturation magnetization, Ms, and magnetic susceptibility��m=�m� + i�m� , particularly �m� �, which are directly relevantto the �Tac,mag characteristics, can be easily controlled byadjusting the relative concentration of Mn2+ and Zn2+ cationsin the MnxZn1−xFe2O4.6,8,9 However, all of the works rel-evant to the MnxZn1−xFe2O4 done so far were entirely fo-

cused on magnetoelectronics device applications.10 Therehave been no systematic studies on the magnetic properties,�Tac,mag characteristics, and the biocompatibility ofMnxZn1−xFe2O4 SPNPs for MH agent applications until now.

In this paper, we report on the effects of Mn2+ cationconcentration on the magnetic properties and the �Tac,magcharacteristics of MnxZn1−xFe2O4 SPNPs to explore its fea-sibility as a MH agent. The physical correlation between themagnetic properties of MnxZn1−xFe2O4 SPNPs controlled bythe Mn2+ cation concentration and �Tac,mag, characteristicsincluding power loss mechanism were systematically inves-tigated at different ac Happl and fappl. In addition, the cellviability of MnxZn1−xFe2O4 SPNPs with different Mn2+ cat-ion concentrations were quantitatively analyzed to evaluatethe biocompatibility for in vivo MH agent applications.

The spinel ferrite MnxZn1−xFe2O4 nanoparticles �NPs�with different Mn2+ cation concentration were synthesizedusing a modified high temperature thermal decomposition�HTTD� method, where ramping up rate and heat treatmenttime were changed to 8.5 °C /min and 25 min, respectively,compared to a conventional HTTD method.11 The Mn2+ cat-ion concentration of MnxZn1−xFe2O4 NPs was systematicallycontrolled from x=0.2 to 0.8 during the synthesis. The crys-tal structure, the particle size, and the distribution ofMnxZn1−xFe2O4 NPs were analyzed by using a Cu-k� radi-ated x-ray diffractometer �XRD� and a high resolution trans-mission electron microscopy �HRTEM�. The �Tac,mag char-acteristics and the ac magnetic hysteresis of the solid stateMnxZn1−xFe2O4 NPs were measured by using an ac solenoidcoil system, which is connected to a capacitor. The fappl andthe Happl were varied from 30 kHz to 210 kHz and from 60Oe to 140 Oe, respectively. The dc magnetic properties of the

a�Author to whom correspondence should be addressed. Electronic mail:elebst@nus.edu.sg.

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solid state MnxZn1−xFe2O4 NPs were analyzed by using avibrating sample magnetometer and the ac �m was measuredby using an ac magnetosusceptometer. The zero fieldcooling/field cooling �ZFC/FC� measurement was carried outto characterize the dependence of temperature on the mag-netic properties of MnxZn1−xFe2O4 NPs using a supercon-ducting quantum interference device �SQUID�. The cell vi-ability was quantitatively analyzed by employingthe methylthiazol tetrazolium bromide test �MTT� usingneuronal stem cells �NSCs� isolated from human fetal mid-brain. The MnxZn1−xFe2O4 NPs were dispersed into themixed media of 2.5% alcohol, Dulbeco’s modified eagle’smedium, 10% fetal bovine serum, 1% penicillin streptomy-cin, and 2 mM glutamine. The concentration ofMnxZn1−xFe2O4 NPs in the media were variedfrom 5 to 25 �g /ml.

Prior to studying the magnetic properties and the�Tac,mag characteristics, the crystal structure, the particle sizeand the distribution of MnxZn1−xFe2O4 NPs were first inves-tigated. As can be seen in Fig. 1, all of the MnxZn1−xFe2O4NPs had a mean particle size of 5.7–6 nm with a 12% stan-dard deviation and they were well segregated with a roundshapes. In addition, the MnxZn1−xFe2O4 NPs showed a singlephase cubic spinel ferrite structure and did not exhibit anyundesirable crystalline phases. The well controlled structuraland chemical stabilities of MnxZn1−xFe2O4 NPs demonstratethat they can be considered to be an in vivo MH agent be-cause they are expected to minimize the biochemical reac-tion with chemical components in the blood stream and toallow for stable intravenous circulation.

Figure 2 shows the hysteresis loops of MnxZn1−xFe2O4NPs measured under an externally applied field of �a�=�10 kOe and �b� =�80 Oe at room temperature. All ofthe MnxZn1−xFe2O4 NPs had superparamagnetic �SP� prop-erties. Furthermore, the ZFC/FC measurement results �notshown in this paper� confirmed that the blocking temperatureof MnxZn1−xFe2O4 NPs is in the range of 80–120 K depend-ing on the Mn2+ cation concentration, indicating that theyhave a SP phase at room temperature. As shown in Fig. 2�a�,the Ms had a strong dependence on the Mn2+ cation concen-

tration. Particularly, the Mn0.5Zn0.5Fe2O4 NPs had the high-est Ms value of a 47 emu/g. The increase in Ms by increasingthe Mn2+ cation concentration up to x=0.5 is thought to bedue to the increase in magnetic moment of the unit cell up to7.5 �B ��B: Bohr magneton� which resulted from the re-placement of Zn2+ ions by Mn2+ ions on the A-site. However,increasing the Mn2+ cation concentration above x=0.5 wasfound to decrease the Ms. This decrease in Ms is due to thedevelopment of antiferromagnetic alignment of Fe3+ ions onthe B-site �see Fig. 3�c��.6

Figure 3 shows the dependence of Mn2+ cation concen-tration on the �Tac,mag and the magnetic properties ofMnxZn1−xFe2O4 SPNPs. In Fig. 3�a�, it can be clearly ob-served that the �Tac,mag measured at a constant Happl=80 Oe, fappl=210 kHz had a strong dependenceon the Mn2+ cation concentration. The �Tac,mag ofMnxZn1−xFe2O4 SPNPs was increased by increasing the Mnconcentration and reached a maximum �Tac,mag=39 °C atthe composition of Mn0.5Zn0.5Fe2O4. A further increase inMn concentration, x0.5, led to a severe reduction in�Tac,mag. The physical dependence of fappl and Happl on the�Tac,mag is shown in Fig. 3�b�. It was clearly demonstratedthat the �Tac,mag is linearly proportional to the fappl andsquarely proportional to the Happl. These results strongly im-ply that the physical nature of �Tac,mag of MnxZn1−xFe2O4

FIG. 1. HRTEM images and XRD patterns of synthesized superparamag-netic MnxZn1−xFe2O4 nanoparticles with different Mn composition: �a� x=0.33, �b� x=0.5, �c� x=0.67, and �d� XRD patterns.

FIG. 2. Magnetic hysteresis loops of MnxZn1−xFe2O4 nanoparticles withdifferent Mn2+ cation concentration changed from x=0.2 to 0.8. �a� Majorloop and �b� minor loop.

FIG. 3. Dependence of Mn2+ cation concentration on the �a� ac magneticallyinduced heating characteristics measured at the fixed Happl=80 Oe andfappl=210 kHz, �b� applied frequency and magnetic field, and �c� SAR,heating power �total and relaxation loss�, magnetization, out of phase sus-ceptibility and ac magnetic coercivity of superparamagnetic MnxZn1−xFe2O4

nanoparticles �� SAR, � magnetization �dc�, � Ptotal, � Prelaxation loss, � acsusceptibility, and � coercivity �ac��.

202511-2 Jeun et al. Appl. Phys. Lett. 96, 202511 �2010�

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SPNPs is dominantly related to the “relaxation loss” heatingpower, Prelaxation loss, as described in Eqs. �1� and �2�.12 Fur-thermore, from this point of view, the highest �Tac,mag valueobtained from the Mn0.5Zn0.5Fe2O4 SPNP can be understoodto be due to its highest measured �m� value which resultedfrom its softest magnetic property as well as its largest ex-change energy induced by the half portion of Zn2+ ions re-placed by the Mn2+ ions on the A-site.

Prelaxation loss = �0�m� fapplHappl

2 , �1�

�� = �02f�

1 + �2f��2 ,1

�=

1

�N+

1

�B�

1

�N

=2�KuV/kBT

� · �0 exp�KuV/kBT�,�soft ferrite:�N � �B� , �2�

where �N: Néel relaxation time, �B: Brownian relaxationtime, �0:relaxation factor, and Ku: magnetic anisotropy.

The ac magnetic coercivity of MnxZn1−xFe2O4 SPNPsmeasured at Happl= �80 Oe and fappl=210 kHz is shown inFig. 3�c�. The Mn0.5Zn0.5Fe2O4 SPNP exhibited the smallestac magnetic coercivity among the MnxZn1−xFe2O4 SPNPsindicating that it has the lowest ac magnetic anisotropy re-sulting in the fastest �N �or the highest �m� described in Eq.�2��. This experimental result provides strong physical evi-dence that the highest �Tac,mag of Mn0.5Zn0.5Fe2O4 SPNP�x=0.5� is related directly to the well-controlled highest �m� .Furthermore, this indicates that controlling the ac magneticsoftness of SPNPs, which is directly relevant to the Néelrelaxation behavior, is the most crucial factor in determiningthe �Tac,mag characteristics. In order to further clarify thephysical mechanism of �Tac,mag of MnxZn1−xFe2O4 SPNPs,the contribution of Prelaxation loss to the total power heat gen-eration, Ptotal, was numerically compared by calculating bothPtotal and Prelaxation loss from the experimentally obtained�Tac,mag, �m� �at fappl=210 kHz�, mass, and the volumetricheat capacity values of MnxZn1−xFe2O4 SPNPs. As can beseen in Fig. 3�c�, more than 80% or 90% of Prelaxation losscontributed to the Ptotal of MnxZn1−xFe2O4 SPNPs verifyingthat the Prelaxation loss, particularly the Néel relaxation powerloss is dominant for the �Tac,mag of MnxZn1−xFe2O4 SPNPs.To consider the SPNPs for a real clinical MH agent withoutsystemic side effect, the SPNPs should generate a higher�Tac,mag both in a short heat up time and with a amount aslow as possible. These characteristics can be evaluated by theSAR shown in Fig. 3�c�.13 The Mn0.5Zn0.5Fe2O4 SPNPshowed the largest SAR value of 138.4 W/g due to the fastesttemperature rising rate ��T /�t� caused by the highest ��value among the MnxZn1−xFe2O4 SPNPs. This value is con-sidered to be much higher than those obtained from the con-ventional ternary phase SPNAs at the same ac condition,e.g., Fe3O4 �27.3 W/g�, CoFe2O4 �56.1 W/g�, and NiFe2O4�12.6 W/g�.14

The cell viability of MnxZn1−xFe2O4 SPNPs with differ-ent concentrations was quantitatively estimated to explorethe feasibility to a MH agent particularly targeted for braintumors. Figure 4 showed the cell survival rate treated for �a�one day and �b� two weeks, respectively. It was clearly con-firmed that the cell survival rate of MnxZn1−xFe2O4 SPNPs

depends on the concentration of NPs in the cell culture me-dia as well as the Mn2+ cation concentration. All three SP-NPs showed midcytotoxicity or noncytotoxicity. In particu-lar, the Mn0.5Zn0.5Fe2O4 SPNP had the highest cell survivalrate of 80%�8% �10% of standard deviation� even at ahigher NP concentration and for a long treatment time. Thehigher cell survival rate of Mn0.5Zn0.5Fe2O4 SPNP is thoughtto be due to the chemically stable phase of Mn0.5Zn0.5Fe2O4,which is expected to induce less stress on the cells and thelarge portion of Mn2+ cation concentration, which is consid-ered to have a high biocompatibility.15

In conclusion, it was demonstrated that the �Tac,mag andthe magnetic properties of MnxZn1−xFe2O4 SPNPs had astrong dependence on the Mn2+ cation concentration. Amongthe MnxZn1−xFe2O4 SPNPs, the Mn0.5Zn0.5Fe2O4 SPNPshowed the highest �Tac,mag, SAR, and biocompatibility,which make it suitable for MH agent applications. Thehigher �� value directly relevant to the �N �or ac magneticsoftness� and the higher chemical stability systematicallycontrolled by the replacement of Zn2+ cations by the Mn2+

cations on the A-site are the primary physical reason for thebiotechnical promises of Mn0.5Zn0.5Fe2O4 SPNP.

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FIG. 4. Cell viability of superparamagnetic MnxZn1−xFe2O4 nanoparticles�x=0.33, 0.5, and 0.67� in MTT assay with NSCs isolated from human fetalmidbrain treated for �a� one day and �b� two weeks.

202511-3 Jeun et al. Appl. Phys. Lett. 96, 202511 �2010�

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