Modulation of Magnetic Heating via Dipolar Magnetic Interactions in Monodisperse and Crystalline...

Modulation of Magnetic Heating via Dipolar Magnetic Interactions inMonodisperse and Crystalline Iron Oxide NanoparticlesGorka Salas,†,‡ Julio Camarero,†,§ David Cabrera,† Helene Takacs,†,‡ María Varela,∥,⊥ Robert Ludwig,#

Heidi Dahring,# Ingrid Hilger,# Rodolfo Miranda,†,§ María del Puerto Morales,‡

and Francisco Jose Teran*,†,%

†IMDEA Nanociencia, Campus Universitario de Cantoblanco, 28049 Madrid, Spain‡Instituto de Ciencia de Materiales de Madrid-CSIC, C\Sor Juana Ines de la Cruz, 5 Campus Universitario de Cantoblanco, 28049Madrid, Spain§Dpt. Física de la Materia Condensada and Instituto Nicolas Cabrera, Universidad Autonoma de Madrid, Campus Universitario deCantoblanco, 28049 Madrid, Spain∥Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States⊥Dpt. Física Aplicada III & instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain#Institute for Diagnostic and Interventional Radiology I, Jena University Hospital, Friedrich Schiller University of Jena, Bachstraße 18,D-07740 Jena, Germany%Unidad Asociada de Nanobiotecnología CNB-CSIC & IMDEA Nanociencia, Campus Universitario de Cantoblanco, 28049 Madrid,Spain

*S Supporting Information

ABSTRACT: In the pursuit of controlling the heat exposuremediated by magnetic nanoparticles, we provide new guidelines fortailoring magnetic relaxation processes via dipolar interactions. Forthis purpose, highly crystalline and monodisperse magnetic ironoxide nanocrystals whose sizes range from 7 to 22 nm weresynthesized by thermal decomposition of iron organic precursors in1-octadecene. The as-synthesized nanoparticles are soft nano-magnets, showing superparamagnetic-like behavior and SAR valueswhich progressively increase with particle size, field frequency, andamplitude up to 3.6 kW/gFe. Our data show the influence of mediaviscosity, particle size, and concentration on dipolar interactions andconsequently on the magnetic relaxation processes related to theheat release. Understanding the role of dipolar interactions is of greatimportance toward the use of iron oxide nanoparticles as efficienthyperthermia mediators.

1. INTRODUCTION

Iron oxide nanoparticles (IONP) are finding a rapidlyincreasing number and variety of biomedical applications1,2

due to their size-driven colloidal and magnetic properties at thenanoscale.3−5 The precise control of IONP size and coatingengineering6 favor their internalization into cells withoutcytotoxicity drawbacks.7,8 These features render IONP as asuitable platform for simultaneously acting as imaging contrastagents,9,10 drug-delivery nanocarriers,11,12 and intracellularhyperthermia mediators.9,13−15 For the latter application, theconversion of electromagnetic energy into heat taking place iniron oxide nanocrystals has proven to successfully removetumors13−15 and/or control cellular machinery.16

In the past 20 years, the use of magnetic heating mediated byIONP for therapeutic purposes has experienced a vastdevelopment. IONP have eventually reached clinical trials13,14

thanks to the progress in materials science4,5,17 for producingbiocompatible nanoparticles with optimal magnetic properties18

and in cell biology for assessing the biological activity ofIONP.2,7,8 Nowadays, IONP have a great potential as aminimally invasive and local heating generators13−15 underalternating magnetic fields (HAC) at moderate frequencies ( f)and amplitudes (μ0H) in order to preserve patient comfort andsafety.19 The forthcoming clinical potential of heating mediatedby IONP relies on three aspects. First, the heat release shouldbe the highest possible at the lowest IONP dose. Second,uniform size and morphology are required to providehomogeneous heat dissipation power according to each

Received: April 28, 2014Revised: July 23, 2014Published: July 23, 2014

Article

pubs.acs.org/JPCC

© 2014 American Chemical Society 19985 dx.doi.org/10.1021/jp5041234 | J. Phys. Chem. C 2014, 118, 19985−19994

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IONP dose. Third, heating mechanisms should not beinfluenced by the biological matrix (i.e., cells or tissues whereIONP are located) in terms of viscosity and aggregation. Anyimprovement in the chemical synthesis of IONP to strengthentheir magnetothermal properties and to control their heat lossmechanisms is of paramount relevance for their application asmagnetic heating mediators. In order to achieve these goals, bigefforts are paid to obtain highly crystalline and narrow sizedistribution IONP with large saturation magnetization values(MS). Thermal decomposition routes20,21 allow to obtaincrystalline IONP22 due to the high temperature of the chemicalreaction which favor both crystal growth and size distributionnarrowing, leading to high values of MS and heatingefficiency.23,24 Recent strategies to enhance MS and heatingefficiency are based on manipulation of the exchange couplingin core−shell nanoparticles15 or cooperative phenomena.9,25−27

The latter strategy takes advantage of the collective nano-particle behavior mediated by magnetic dipolar interactions,which enhance the heat efficiency under certain condi-tions.9,25,27,28 Understanding the role of dipolar interactions ishighly crucial for the application of magnetic nanoparticles inbiomedicine.26,27 After cell uptake, IONP are located insidesubcellular vesicles forming large aggregates29,30 whereinterparticle interactions negatively influence their magneticproperties,29and consequently their contrast signal30 and/orheating efficiency.31

A precise control of the heat exposure is mandatory for theclinical translation of magnetic heating mediated by IONP. Thiscondition is met when the nature of heating mechanismsremains invariable under distinct environmental conditionssuch as viscosity or aggregation. Different magnetic relaxationprocesses govern heat dissipation in magnetic nanoparticles32,33

depending on distinct parameters such as particle size,dispersion media viscosity, and magnetic properties. In thecase of superparamagnetic IONP, magnetic moment relaxationmechanisms involved in heat dissipation can be described interms of Brown and Neel processes.34 These relaxationprocesses are related to different physical phenomena. Onone hand, Brown relaxation is due to thermally drivenreorientation (i.e., physical rotation of the particle) in thedispersion media while the magnetic moment is locked ontothe crystal anisotropy axis. On the other hand, Neel relaxationis related to the internal reorientation of the particle magneticmoment due to thermal fluctuations across the anisotropicbarrier of the particle magnetic moment. Neel magneticrelaxation processes depend on particle volume (V), temper-ature (T), and effective magnetic anisotropy (Keff), while Brownrelaxation processes depend on hydrodynamic volume,dispersion media viscosity (η), and T. In general, bothrelaxation processes coexist until one of them shows smallerrelaxation rates and then dominates. Typically, heatingmechanisms evolve from Neel to Brown processes whenincreasing size and Keff.

34 However, Neel relaxation processesare favored when the field amplitude is larger than theanisotropy field.35

Here, we report on the study of the magnetothermalproperties of highly crystalline and monodisperse IONP whosecore sizes range from 7 to 22 nm. IONP were synthesized bythermal decomposition method previously reported.23 Thestudied IONP are highly uniform in size and morphology,showing extremely good crystalline features. In addition, IONPshow superparamagnetic-like behavior with MS values around70 emu/gmagh and specific absorption rate (SAR) values of

several kW/gFe at extreme HAC conditions (435 kHz and 40mT). By varying the viscosity of the IONP dispersion media,we assess the heating efficiency and mechanisms as a functionof particle size and concentrations. Thus, we prove that Neelrelaxation dominates the heating mechanism for all IONP sizes.Our results underline that dipolar interactions are significantlyfavored when increasing IONP core size and concentration.

2. MATERIALS AND METHODSSynthesis of Magnetic Iron Oxide Nanoparticles.

IONP with core size of 7 nm were synthesized by thermaldecomposition of Fe(acac)3 following Sun’s method,

21 but withmechanical stirring instead of magnetic stirring, using 1,2-dodecanediol instead of 1,2-hexadecanediol and with 1-octadecene as solvent. IONP of larger sizes from 12 to 22nm were synthesized by a thermal decomposition ofFe(oleate)3 described by Park et al.20 but including somemodifications.23 The resulting hydrophobic IONP weresubsequently transferred to aqueous media after a ligandsubstitution procedure with meso-2,3-dimercaptosuccinic acid(DMSA).23 DMSA coating provides biocompatible features7,36

and high colloidal stability for months.Structural Characterization. Particle size and shape were

examined by transmission electron microscopy (TEM) 200 keVmicroscopes JEOL JEM 2000 FXII and JEOL JEM 2100.Samples were prepared by placing one drop of a dilutesuspension of the hydrophobic particles in hexane onto acarbon-coated copper grid and leaving it to dry at roomtemperature. The size distributions were determined throughmanual analysis of ensembles of over 300 particles found inrandomly selected areas of the enlarged micrographs, withImageTool software (UTHSCSA) to obtain the mean size andstandard deviation. Atomic resolution scanning TEM imageswere acquired in a Nion UltraSTEM200 equipped with aspherical aberration fifth-order corrector and a Gatan EnfiniumEEL spectrometer. A Nion UltraSTEM100 operated at 60 kVand equipped with a Nion aberration corrector and a GatanEnfina spectrometer was also used.

Colloidal Characterization and Hydrodynamic SizeVariation. The ligand substitution process allows to transferthe synthesized IONP to aqueous dispersions with some degreeof IONP aggregation. Thus, dynamic light scattering (DLS)was employed to measure such aggregation degree expressed bythe hydrodynamic size (DH). A Malvern Zetasizer Nano ZS90was employed for measuring DH in the studied IONP in diluteparticle water suspensions (<0.5 mgFe/mL) at pH 7 placed in astandard cuvette. The energy source was a laser emitting agreen light, and the angle between the sample and detector was173°. The variation of DH in IONP suspensions was achievedby changing the pH36 and/or by adding a phosphate bufferedsaline (PBS) solution (<1%)23 without altering the dispersionviscosity and specific heat. Surface charge of DMSA-coatedIONP diminishes when reducing pH down to 4, leading to anincrease of DH from 50 nm at pH = 7 up to 180 nm at pH = 4.In a similar way, we increase DH by adding PBS from 40 nm (at0% PBS) up to 140 nm (at 0.5% PBS). In all cases, the colloidalstability of particle dispersions was preserved for at least 24 h.Magnetization measurements under quasi-static conditions ofIONP aggregates (DH = ∼50 nm) dispersed in water and inagar allow to monitor the influence of agar in the aggregationstate (i.e., DH). In the Supporting Information, Figure S2 showsa larger coercive field for the agar dispersion than in (frozen)water at 250 K. This can be interpreted as due to a slight

The Journal of Physical Chemistry C Article

dx.doi.org/10.1021/jp5041234 | J. Phys. Chem. C 2014, 118, 19985−1999419986

increase of the aggregation state in agar dispersion with respectto water, which results in an extra anisotropy contribution dueto magnetic dipolar interactions. Thus, we expect that in agardispersions IONP aggregates would have slightly larger DHvalues than in water.Magnetic Characterization. Magnetic characterization of

the IONP samples dispersed in water (volume of 100 μL, ironcontent ranging between 2 and 3 mgFe/mL) under quasi-staticconditions was carried out in a vibrating sample magnetometer(VSM, Oxford Instrument MLVSM9MagLab 9 T). Magnet-ization curves were recorded for a sweeping magnetic field rateof 5 mT/s at T = 10 and 250 K after saturating the IONPmagnetization under external and static magnetic fields of 5 T.Magnetization units are expressed in emu per gram ofmaghemite (γ-Fe2O3). Thus, we enclose the lower limit valueof MS since IONP are a mixture of γ-Fe2O3 and Fe3O4(magnetite).23 MS values were evaluated by extrapolating toinfinite field the experimental results obtained in the high fieldrange where the magnetization linearly increases with 1/H.Zero field cooling/field cooling (ZFC/FC) measurements wereperformed in a temperature range from 5 to 260 K measuringmagnetization while increasing T under a static magnetic fieldof μ0H = 10 mT. Within this thermal range, the IONPdispersions are frozen and magnetization measurements can beprecisely realized. In addition, we have performed magnet-ization measurements for checking the influence of agar on theaggregation state of IONP dispersions. Magnetization cycles ofIONP dispersed in agar (4%) and water dispersions at 250 K atcomparable IONP concentrations (3 mgFe/mL) were measured(see Figure S2). Finally, measurements of magnetization cyclesunder dynamical conditions (100 kHz and 40 mT) wereperformed in a homemade set up similar to the one describedby Mehdaoui et al.37 HAC was generated by an air-cooled Litzwire coil. Inside this coil, two contrariwise-woundedcompensated pick-up coils connected in series were set. Bothpick-up coils have the same diameter and number of turns. Thesystem quantifies the magnetic signal of a 50 μL volume ofIONP solution allowing to compare magnetization cycles fromIONP dispersed in water and agar under HAC conditions similarto those employed for SAR measurements.Calorimetry Measurements. SAR values of IONP

dispersions have been determined by nonadiabatic calorimetricmeasurements. In the present study, calorimetric measurementshave been performed on reduced volumes of IONP dispersedin water and agar at different IONP concentrations. Twodifferent setups have been used: (i) A homemade frequencyand amplitude adjustable system with frequencies up to 180kHz and field amplitudes up to 50 mT described elsewhere.38

The setup requires a reduced sample volume (35 μL) allowingto control and quantify the heat loss mechanisms. Temperaturechanges after applying HAC were monitored via a commercialoptical fiber probe TS2/2 connected to a FOTEMP2-16 two-channel signal conditioner from Optocon AG with anexperimental error of ±0.2 °C. (ii) A homemade water cooledgenerator at fixed frequency of 435 kHz and adjustable fieldamplitudes up to 40 mT. These experimental arrangementswere used to obtain SAR values using reduced volumes (200μL) of the respective particle dispersions in water and agar.Temperature changes after applying HAC were monitored via acommercial optical fiber probe TS5 connected to aFOTEMPMK-19 from Optocon AG, with an experimentalerror of ±0.2 °C. The methodology for extracting SAR values isbased on repeating three times the time variation temperature

curves of IONP dispersions at given particle mass and HACconditions. Thus, we extract the values of the maximal slope atinitial times after switching on HAC (i.e., dT/dt|max) fordetermining its average value and standard deviation. After-ward, SAR values are determined by using the expression

=C mm

Tt

SARdd

d d

Fe max (1)

where Cd is the volumetric specific heat of the dispersion media,md is the mass dispersion, and mFe is the iron mass diluted inthe dispersion and dT/dt|max is the average value of the maximalslope at initial times after switching on HAC. The volumetricspecific heat constant for water and 1% and 10% agardispersions was measured at the Servicio Interdepartamentalde Investigacion from Universidad Autonoma de Madridobtaining the following values: C1% = 4.18 ± 0.05 J/(g K)and C10% = 3.78 ± 0.08 J/(g K), respectively.

3. RESULTS AND DISCUSSIONAqueous Colloidal Suspensions of Uniform and

Highly Crystalline IONP. Highly crystalline and uniformmagnetic iron oxide nanocrystals whose size (d0) ranges from 7to 22 nm were synthesized by thermal decomposition of ironorganic precursors in 1-octadecene. The resulting IONP are amixture of magnetite (Fe3O4) and maghemite (γ-Fe2O3) whoseratio increases with particle size as expected.39,40 Figure 1 showTEM micrographs and size distribution of the studied IONP. Itis worth noting the uniform size and morphology for all sizesand also how IONP shape changes with size. Whereas IONPwith d0 ≤ 12 nm display almost spherical shape, larger particlesizes show cubic (d0 = 14 and 18 nm), octahedral (d0 = 18 nm),and/or truncated octahedral (d0 = 22 nm) shapes.23

Recent work carried out by Varela et al.22 shows the highdegree of atomic order on small particles synthesized by similarmethods whose size ranges from 5 to 10 nm. Similar atomicorder has been also observed in this work for larger sizes (i.e.,d0 ≥ 12 nm). As shown in Figure 2, our IONP are highlycrystalline all the way to the surface and consist of singlecrystallographic domains. Crystalline IONP are associated withhigh values of crystalline anisotropy leading to large values ofMS and Keff at room temperatures due to the high structuralorder.41 Electron energy-loss spectroscopy provides composi-tional maps with sensitivity to the different elements of interest.Thus, the DMSA coating can be observed at the particle surfaceas an amorphous-like phase in the form of a homogeneouscoverage both in the bright field images and also in thecompositional maps. Besides, the coating leads to some degreeof IONP aggregation in water suspension as expressed by theDH values, which range from 45 to 66 nm for DMSA coatedIONP with distinct sizes (see Table 1).

Effect of Particle Core Size on the Magnetic Behaviorof IONP Suspensions. Magnetization curves of the studiedIONP have been characterized by VSM at T = 5 and 250 K asshown in Figure 3. On the one hand, MS values very close to 70emu/gmagh are observed beyond μ0H = ±2.5 T near roomtemperatures for all IONP sizes studied. Indeed, MS valuesslightly change with d0 varying from 66 emu/gmagh (d0 = 7 nm)up to 69 emu/gmagh (d0 = 22 nm). At the same time, MS valuesare not sensitive to temperature increasing around 4% whenlowering temperature to 10 K as shown in Figure 3b. On theother hand, HC and remanent magnetization (MR) values arenegligible at 250 K for all sizes, suggesting superparamagnetic-



like behavior at room temperatures. However, the opening ofmagnetization cycles is well pronounced at low temperatures(T = 5 K), reaching a maximum value of HC = 36 mT for d0 =22 nm (see Figure 3b).Blocking temperatures (TB) can be determined from ZFC-

FC measurements42 (see Figure S1 in Supporting Information).As shown in Table 1, a progressive shift of TB from 70 K totemperatures higher than 270 K was observed when increasingIONP size from d0 = 7 to 22 nm. Approximate values of Keff canbe derived from TB

43 for the sake of a qualitative comparisonwith respect to particle size (see Table 1) in a set ofmonodispersed IONP. All Keff values are larger than thosereported for bulk magnetite and maghemite (1.1 and 0.46 × 104

J/m3, respectively). Keff display bigger values for the smallest d0,which can be understood in terms of a larger surface anisotropycontribution, whereas the largest d0 show Keff values closer tothe bulk. These results are in agreement with the high atomicorder observed in Figure 2 throught the whole IONP volume(i.e., surface and core). In spite of the smaller Keff valuesobtained from TB at large IONP sizes, anisotropic energy

barrier (i.e., KeffV) is up to 4 times larger for d0 = 22 nm thanthose for d0 = 7 nm (see Table 1). The evolution of KeffV withd0 underlines the importance of size for defining IONPmagnetic properties under dynamical magnetic field conditions.Finally, Figure S1 shows the Verwey transition at temperaturesaround 90 K only for particles of d0 = 18 and 22 nm wheremagnetite becomes relevant in composition ratio as reportedelsewhere.23

Size and Field Dependence of SAR. The determinationof SAR values as a function of d0, HAC conditions, and ironconcentration has been performed by nonadiabatic calorimetrymeasurements in reduced volumes of IONP dispersed in waterand agar. Figure 4 shows the field-amplitude dependences ofSAR values for IONP of different d0 and comparable DH (seeTable 1) dispersed in water at moderate HAC conditions ( f = 77kHz) and given iron content (10 mgFe/mL). SAR valuesprogressively increase with d0 and field amplitude up to 320 W/gFe for the largest size at 50 mT. It is worth mentioning thatthese SAR values are reached for Hf ≈ 3 × 109 A/(m s), wellbelow the comfort patient factor threshold (Hf = 5 × 109 A/(ms)).19 Depending on the field amplitude, SAR reaches maximalvalues at different d0. Thus, for μ0H = 10 mT, the maximumSAR value is observed at d0 = 14 nm, whereas for μ0H = 20 mT

Figure 1. Selected TEM micrographs and histograms of normalizedIONP size distributions. Scale bars = 50 nm.

Figure 2. High-resolution high angle annular dark field image(HAADF), along with simultaneously acquired annular bright fieldimages (ABF) of a single IONP, obtained in a dedicated scanningtransmission electron microscope (STEM) operated at 200 kV. Theparticles were hanging over a hole, allowing spectroscopic mapping ofthe surface C. The lower panel shows a low-magnification HAADFimage along with Fe and C compositional maps, overlaid in a matchingscale. Fe (C) maps have been obtained from electron energy lossspectrum (EELS) images including the Fe L2,3 and the C K edges.EELS data were acquired at 60 kV.



the maximum SAR value is observed at d0 = 18 nm. For μ0H >20 mT, maximum values of SAR are expected for d0 > 22 nm.Such behavior has been described in terms of a Stoner−Wohlfarth model where V, Keff, and MS values drive the SARsize dependence at given HAC conditions.44 In addition, theheat losses per cycle (SAR/f)45 is related to the area ofhysteresis loops. It reaches values up to 4.16 J/kgFe for d0 = 22nm, revealing a remarkable sensitivity (up to 1000-fold) of theopening of magnetization cycles for increasing sizes atmoderate HAC conditions (see Table 1).SAR can be also expressed in terms of the intrinsic loss

power (ILP), which is a physical magnitude to compare heatingefficiencies obtained under different HAC conditions.46 ILP isgiven by the expression ILP = SAR/f H2, where f and H are theapplied field frequency and amplitude, respectively. Theconversion of SAR into ILP values has a proper meaningwithin the limits of linear response theory (i.e., when maximum

Table 1. Summary of d0, DH, MS, TB, Keff, KeffV, SAR/f, and ILP Values Obtained from the Studied IONP

d0 (nm) DH (nm)/PDI MSa (emu/gmagh) TB (K) Keff (×10

4 J/m3) KeffV (10−20 J) SAR/fb (J/kg) ILPb (nHm2/kg)

7 ± 1 62/0.18 64 70 13.5 2.43 0.06 0.0412 ± 1 49/0.22 66 140 5.3 4.83 0.21 0.1314 ± 1 45/0.15 69 200 4.8 6.90 0.82 0.5218 ± 2 66/0.18 70 >260−300 2.9−3.4 8.9−10.4 1.61 1.0222 ± 2 48/0.17 69 >260−300 1.6−1.9 8.9−10.6 4.16 (7.03)c 2.60 (6.87)c

aValues at T = 250 K. bValues shown in Figure 4 at f = 77 kHz, 50 mT, and 10 mgFe/mL.cObtained from data shown in inset Figure 6.

Figure 3. Maghemite mass-normalized magnetization cycles (a) for different IONP sizes at temperature of 250 K and (b) for d0 = 22 nm size at T =5 and 250 K. Insets: details of the magnetization curves at low magnetic fields.

Figure 4. Magnetic field amplitude and size dependence of SAR andSAR/f obtained for IONP dispersed in water at given IONPconcentration (10 mgFe/mL) and f = 77 kHz.

Figure 5. Magnetic field amplitude dependence of SAR values obtained for IONP dispersed in water (black circles) and agar (red circles) at IONPconcentration of 10 mgFe/mL and f = 77 kHz for different sizes (a) d0 = 14 nm, (b) d0 = 18 nm, and (c) d0 = 22 nm. (d) SARwater (black empty bars)and ΔSARvis values (blue solid bars) at different d0 and similar HAC conditions ( f = 77 kHz and 50 mT).



applied field amplitude is much smaller than magnetic field atwhich the magnetization saturates).47 As observed in Figure 3a,a MS value is reached for all IONP sizes beyond 1 T. Thus, theHAC conditions employed in this work ( f ≤ 435 kHz and μ0H≤ 50 mT) fit within the limits of the linear response theory forall IONP studied. Kallumadil et al.46 show that particles withILP values beyond 1 are good candidates as hyperthermiamediators. ILP values of the studied IONP range from 0 up to8.15 depending on d0, dispersion viscosity, and field conditionsas shown in Table 1. At moderate conditions, the maximal ILPvalues are 2.60 nH m2/kgFe for d0 = 22 nm. However, underextreme HAC conditions (435 kHz and 40 mT), the maximalILP values are 6.87 (water) and 8.15 nH m2/kgFe (agar) for d0= 22 nm, which are among the highest values reported so far.Besides, heating mechanisms of superparamagnetic nano-

particles are typically related to Neel and Brown relaxationprocesses.32 Calorimetry measurements allow to distinguishamong both relaxation processes when varying the viscosity ofthe IONP dispersion because it affects particle rotation.34

Therefore, one expects to observe differences in the heat releasefrom free-standing and immobilized IONP.Particle Size Effects on Magnetic Relaxation Pro-

cesses. In order to assess the influence of η on heat dissipationpower, we have measured SAR values for IONP with differentsizes and iron content. IONP were dispersed in water, whereparticles are ideally free, forming a stable colloids and agar,where particles are ideally immobilized. Figure 5 shows SARvalues obtained in water (SARwater) and agar (SARagar) forIONP with d0 ranging from 14 up to 22 nm under moderateHAC conditions and a given iron content (10 mgFe/mL). TheSAR field dependence vary with particle size observing a linearfield behavior at d0 = 14 nm while at d0 = 22 nm the fielddependence is parabolic-like. Such distinct field evolution withsize is understood in terms of the Stoner−Wolfhart modelwhere anisotropy field is a crucial parameter defining the SARfield dependence.31,44 In addition, the maximal SAR valuessignificantly increase with size as shown in Figure 5.Simultaneously, comparable SAR values at any field amplitudeare observed for IONP dispersed in water (black circles) andagar (red circles) with sizes d0 = 14 and 18 nm. This indicatesthat heating mechanisms are not significantly influenced byviscosity, which is a clear indication of Neel relaxationprocesses.32,34 However, SAR values significantly differ inwater and agar dispersions for d0 = 22 nm, reflecting theinfluence of viscosity on the heat released from the largestIONP when μ0H > 10 mT. Indeed, SAR values in agar

progressively decrease (up to 70%) with respect to the valuesmeasured in water dispersions, being larger in water. The SARvariation related the viscosity increase (ΔSARvis) is betterappreciated by using the following expression:

Δ = ×−

SAR 100SAR SAR

SARviswater agar

water (2)

Figure 5d shows the values of ΔSARvis derived from datacorresponding to different d0 at μ0H = 50 mT shown in Figures5a−c. Interestingly, these results reveal the correlation betweenΔSARvis and particle core size when observing the rapidincrease of values beyond d0 = 18 nm. At first glance, we mayconsider that Brown relaxation is the dominant heatingmechanism for d0 = 22 nm due to the observed SAR viscositydependence. However, it is worth noting the SARagar reductionat 50 mT for d0 = 22 nm (70 W/gFe) with respect to the valuesat d0 = 14 nm (73 W/gFe) and d0 = 18 nm (149 W/gFe). Theseresults do not match the behavior of SARwater at μ0H = 50 mT,which continuously increases with size. Recent works show thatparticle interactions strongly modify SAR values leading tosignificant reductions or enhancements depending on thenature of the particle interactions.9,25−28 The increase ofparticle concentration favors dipolar magnetic interactions,leading to significantly modification of their magnetic relaxationprocesses and consequently their heat dissipation power.Recently, it has been shown that SAR can be influenced byviscosity due to other mechanisms different than Neel−Brownrelaxation rate crossover.25,28 Indeed, the misalignmentbetween easy-axis and particle magnetization directions mayalter magnetic dipolar interactions,25 resulting in a reduction ofheating efficiency.

Interaction Effects on Magnetic Relaxation Processes.In order to determine the influence of particle interactions onheat dissipation mediated by IONP of d0 = 22 nm, we havestudied the SAR field dependences for two IONP concen-trations (2.5 and 10 mgFe/mL) in water and agar dispersions at104 kHz. Figure 6 shows SAR values obtained in water (blackcircles) and agar (red circles) for 2.5 and 10 mgFe/mL ironcontents. First, SARwater and SARagar values are comparable atlow iron concentration (i.e., 2.5 mgFe/mL) in the overall fieldrange, even at the highest frequency (see inset of Figure 6a).SARagar values are slightly larger than SARwater which can beunderstood in terms of the loss susceptibility for noninteractingparticles dispersed in media with different viscosity.32 Second,at high IONP concentration (i.e., 10 mgFe/mL), SARwater values

Figure 6. Magnetic field amplitude dependence of SAR values obtained for d0 = 22 nm dispersed in water (black color) and agar (red color), f = 104kHz and different IONP concentrations (a) 2.5 mgFe/mL), (b) and 10 mgFe/mL, (c) SARwater (black empty bars) and ΔSARvis (blue solid bars)values at different iron content and similar HAC conditions ( f = 104 kHz and 50 mT). Inset: SAR values obtained for f = 435 kHz and 40 mT inwater and agar dispersions for d0 = 22 nm with iron content of 2.5 mgFe/mL.



are up to 3 times larger than SARagar. Thus, one can appreciatethat ΔSARvis values are negligible at low iron content butaround 70% at high IONP concentration. Besides, SARagarvalues at 50 mT show a 50% reduction when increasing ironcontent, contrary to the 100% increased of the SARwater values.According to the fact that SAR = Af, where A is the area of thehysteresis loop43,47−49 when Neel relaxation prevails and theSAR data shown in Figures 6a,b, one may expect the differentmagnetization loops when IONP are dispersed in water or agarat different iron contents. Figure 7 shows the IONP mass-

normalized hysteresis loops of the 22 nm IONP dispersed inwater and agar at two IONP concentrations (2.5 and 10 mgFe/mL) and 104 kHz and 40 mT. At lower iron concentration,similar hysteresis areas A are observed independently ofdispersion media, in agreement with SAR values (see Figures7c,d). However, the area A of hysteresis loops significantlyincreases in water when increasing iron content whereas itdecreases in agar dispersion (see Figure 7b). The shape of themagnetization loops provides some additional information. Theshape of magnetization loops varies with IONP concentrationand viscosity being more elliptical in agar than in water. Suchelliptical shape becomes more pronounced when increasingIONP concentration. This shape is typical from IONP withrandomly oriented anisotropy axis with respect to the externalfield direction.48,49 In order to determine the role ofinterparticle interactions in such experimental results, weconsider the influence of aggregate size and particleconcentration on the heating efficiency.Figure 8 shows the SARagar dependence with DH in agar

dispersions of IONP for d0 = 12 and 22 nm at similar ironcontent (2.5 mgFe/mL) and HAC conditions ( f = 104 kHz and50 mT). At first glance, a clear SARagar reduction is observed forboth particle sizes when DH is increased 3 times. Suchreduction is more pronounced for the largest particles, whereSARagar values diminish more than 30% for d0 = 22 nm incomparison with the 15% reduction for d0 = 12 nm.Interestingly, the SARagar reduction when DH is increased ford0 = 22 nm (33%) is comparable to the one observed in Figure6 when increasing iron content from 2.5 to 10 mgFe/mL

(∼50%). This may imply that such SARagar reduction is relatedto the increase of the number of interacting particles into thecolloidal aggregate of larger DH. Furthermore, we can extracttwo other important messages from Figure 8. First, interactingphenomena become important with particle size according tothe increase of the magnetic moment per particle.40 This is inagreement with the results shown in Figures 5c and 6b. Second,the IONP dispersion viscosity influences the intra-aggregatedipolar interactions. Indeed, the heat dissipated from IONP isoriginated by irreversible magnetization jumps favored bythermal fluctuations across an energy barrier separatingminima.28 The heating release is associated with the numberof jumps occurring due to thermal fluctuations, although theheight of the energy barrier is also relevant. For low-energybarriers or high temperatures, the number of magnetizationjumps related to thermal fluctuations of magnetic moments ofthe nanoparticle ensembles is high, but the heat conversion issmall. However, when barriers are high, the number of particlemagnetic moment relaxation processes is reduced but the heatconversion is higher. The energy barrier across which thermalfluctuations occur generally correspond to the anisotropyenergy barrier for noninteracting particles.50 However, thisenergy barrier is notably influenced by magnetic dipolarinteractions25,26,28 and field amplitude.51 Then, any variationof the energetic barrier related to interacting phenomenasignificantly alter IONP magnetic moment relaxation processesunder dynamical field conditions and consequently the relatedheat dissipation.47 In our particular case, IONP whose sizes aresmaller than 22 nm show nonsignificant influence of dipolarinteractions on their SAR values (see Figure 5). However,interacting effects are significantly appreciated when increasingiron content for 22 nm size IONP. Figure 9 shows the

Figure 7. Iron mass-normalized magnetization cycles of 22 nm sizeIONP dispersed in water (black color) and agar (red color) at f = 104kHz and 40 mT and different IONP concentrations: (a) 2.5 mgFe/mL,(b) 10 mgFe/mL. Comparison of (c) SAR and (d) area A of 22 nm sizeIONP dispersed in water and agar at f = 104 kHz and 40 mT at twoIONP concentrations (2.5 and 10 mgFe/mL).

Figure 8. DH dependence of SAR values obtained for d0 = 12 and 22nm particles dispersed in agar with similar IONP concentration (2.5mgFe/mL) at f = 104 kHz and 40 mT.

Figure 9. IONP concentration dependence of SAR values obtained inwater dispersions for d0 = 22 nm at f = 104 kHz and 40 mT.



evolution of SAR values when increasing iron content in waterIONP dispersions under given HAC conditions (104 kHz and40 mT). Initially, SARwater values remain constant at low IONPconcentration range. Beyond 2 mgFe/mL, SARwater progressivelyincreases with iron content doubling at the highest IONPconcentration (10 mgFe/mL) the value observed at the lowestconcentration (0.3 mgFe/mL). Such behavior can be under-stood as due to variations in the frequency of magneticrelaxation events and the related heat conversion as the dipolarinteractions take place. At low IONP concentrations, theenergy barrier is small (i.e., magnetic field-normalizedanisotropy barrier), leading to a large number of magneticrelaxation processes with a reduced heat conversion. However,when iron content increases, dipolar interactions are favored,and then the energy barrier rises. This leads to a reduction ofthe number of magnetic relaxation events but involves a higherheat release.26,28 Thus, we can understand the results about theevolution of SARwater and area A with IONP concentration interms of the interacting phenomena described by Martinez-Boubeta et al.26 Nevertheless, understanding the reduction ofSARagar and area A values with iron content may imply adifferent scenario. At low iron content, heat dissipation powerin agar is related to the out-of-phase magnetic susceptibilitywhich can be derived from Neel relaxation rate for non-interacting superparamagnets.32 At high iron content, dipolarmagnetic interactions are significantly active as shown in Figure9, influencing magnetic relaxation processes. Recent works25,28

show that dipolar interactions between IONP with softmagnetic properties (i.e., low magnetic anisotropy values)may favor chain formation. Under such conditions, dipolarinteractions are highly sensitive to particle mobility whatstrongly influence their heating efficiency. As mentioned above,IONP dispersed in agar behave as nanomagnets with randomlyoriented anisotropy axis with respect to the external fielddirection or particle magnetization vector. The angle (θ)between easy-axis and magnetization vector is therefore finite inagar dispersions where IONP are immobilized. On thecontrary, IONP dispersed in water where particles are free torotate favoring the aligment between easy-axis and magnet-ization vector (i.e., θ = 0). Magnetization cycles show morepronounced square shape when θ is closer to zero, as observedin Figure 7b. Interacting particles with θ = 0 form chainsdriving a collective behavior that benefits their heatingefficiency9,25,27 while the increase of θ values leads to thereduction of the hysteretic area25 and the heating efficiency. Inour case, we discard the possibility of chain formation for the22 nm size IONP in water at high concentration because theirhigh colloidal stability and the MR is negligible. However, weexpect that heating efficiency shall benefit from the θ reductionobserved for IONP dispersed in water. In that case, SAR valuesshould be larger with respect to immobilized particles in agarwhere θ value should be larger, and therefore SAR valuesshould decrease as shown in Figure 6b. This is in agreementwith the evolution of area A and the magnetization shapeobserved in Figure 7b. In summary, we observe that magneticinteractions favor/affect the easy axis alignment with theparticle magnetization moment when particles are free/immobilized (i.e., in water dispersion).The modulation of dipolar interaction with dispersion

viscosity, particle size, and concentration is of great importancetoward controlling the heat exposure supplied by IONP asintracellular hyperthermia mediators. Cellular processing ofnanoparticles influences their physical properties at the root of

various biomedical applications as recently shown.29−31 Indeed,IONP inside subcellular vesicles form large aggregates thatfavor particle interactions. Our results underline the role ofparticle size, concentration, and dispersion viscosity in magneticdipolar interactions for modulating IONP magnetic relaxationprocesses and consequently their heat dissipation. We haveshown that monodisperse and crystalline IONP constitute asuitable platform for acting as efficient intracellular heatingmediators. Further theoretical models are needed to describehow the dipolar interactions influence SAR and how interactionphenomena depend on particle size, viscosity, and HACconditions.

4. CONCLUSIONSIn this work, we have performed magnetic and calorimetrystudies on highly crystalline and monodisperse IONPsynthesized by thermal decomposition. We have shown thesuperparamagnetic-like behavior near to room temperatures forall particle sizes. SAR values progressively increase with particlesize, field frequency, and amplitude up to 3.6 kW/gFe. Ingeneral, magnetic relaxation processes are dominated by theNeel process for all IONP sizes. However, beyond d0 = 18 nmdipolar interactions are strongly relevant and heating efficiencyvaries with viscosity. The observation of large SAR valuesrelated to Neel relaxation process in monodisperse and highlycrystalline IONP reflects the suitability of thermal decom-position route for providing highly efficient magnetic heatingmediators. Our data show the influence of media viscosity,particle size, and concentration on dipolar interactions andconsequently on the magnetic relaxation processes related tothe heat release. For that purpose, further theoretical works arerequired to describe the influence of dipolar magneticinteractions on IONP heat dissipation as a function of particlesize, dispersion viscosity, and field conditions.

■ ASSOCIATED CONTENT*S Supporting InformationZero field cooling and field cooling magnetization measure-ments for IONP of different sizes; maghemite mass-normalizedmagnetization cycles for IONP dispersed in water and agar.This material is available free of charge via the Internet athttp://pubs.acs.org.

■ AUTHOR INFORMATIONCorresponding Author*E-mail: [email protected] (F.J.T.).Present AddressH.T.: Commissariat de l’Energie Atomique, LETI, CampusMINATEC, 17, avenue des Martyrs 38054 Grenoble Cedex 9,France.Author ContributionsG.S., M.P.M., and F.J.T. conceived and designed the research;G.S., H.T., D.C., J.C., R.L., H.D., M.V., I.H., R.M., M.P.M., andF.J.T. performed the experiments; G.S., M.P.M., and F.J.T.cowrote the paper. All authors discussed the results andcommented on the manuscript.NotesThe authors declare no competing financial interest.

■ ACKNOWLEDGMENTSThis work has been partially supported by EuropeanCommission (MULTIFUN, no. 262943), Spanish Ministry of



http://pubs.acs.org

mailto:[email protected]

Economy and Competitiveness (MAT2010-21822-C02-01,MAT2011-23641, MAT2013-47395-C4-3-R), Madrid RegionalGovernment (NANOBIOMAGNET, S2009/MAT-1726), andthe European Research Council Starting Investigator AwardSTEMOX # 239739. Research at ORNL was supported by theU.S. Department of Energy (DOE), Basic Energy Sciences(BES), Materials Sciences and Engineering Division, andthrough a user project supported by ORNL’s Shared ResearchEquipment (ShaRE) User Program, which is also sponsored byDOE-BES. F.J.T. acknowledges financial support from Ramony Cajal subprogram (RYC-2011-09617). We thank C. Casado,R. Amaro, and L. de la Cueva for technical support and Dr.David Serantes for fruitful discussions.

■ REFERENCES(1) Krishnan, K. M. Biomedical Nanomagnetics: A Spin ThroughPossibilities in Imaging, Diagnostics, and Therapy. IEEE Trans. Magn.2010, 46, 2523−2558.(2) Hilger, I.; Kaiser, W. A. Iron Oxide-Based Nanostructures forMRI and Magnetic Hyperthermia. Nanomedicine 2012, 7, 1443−1459.(3) Frey, N. A.; Peng, S.; Cheng, K.; Sun, S. Magnetic Nanoparticles:Synthesis, Functionalization, and Applications in Bioimaging andMagnetic Energy Storage. Chem. Soc. Rev. 2009, 38, 2532−2542.(4) Roca, A. G.; Costo, R.; Rebolledo, A. F.; Veintemillas-Verdaguer,S.; Tartaj, P.; Gonzalez-Carreno, T.; Morales, M. P.; Serna, C. J.Progress in the Preparation of Magnetic Nanoparticles for Applicationsin Biomedicine. J. Phys. D: Appl. Phys. 2009, 42, 224002.(5) Salas, G.; Veintemillas-Verdaguer, S.; Morales, M. P. RelationshipBetween Physico-Chemical Properties of Magnetic Fluids and TheirHeating Capacity. Int. J. Hyperthermia 2013, 29, 768−777.(6) Luengo, Y.; Nardecchia, S.; Morales, M. P.; Serrano, M. C.Different Cell Responses Induced by Exposure to MaghemiteNanoparticles. Nanoscale 2013, 5, 11428−11437.(7) Calero, M.; Gutierrrez, L.; Salas, G.; Luengo, Y.; Lazaro, A.;Acedo, P.; Morales, M. P.; Miranda, R.; Villanueva, A. Efficient andSafe Internalization of Magnetic Iron Oxide Nanoparticles: TwoFundamental Requirements for Biomedical Applications. Nano-medicine 2014, 10, 733−743.(8) Wilkinson, K.; Ekstrand-Hammarstrom, B.; Ahlinder, L.;Guldevall, K.; Pazik, R.; Kępin ski, L.; Kvashnina, K. O.; Butorin, S.M.; Brismar, H.; Onfelt, B.; et al. Visualization of Custom-TailoredIron Oxide Nanoparticles Chemistry, Uptake, and Toxicity. Nanoscale2012, 4, 7383−7393.(9) Lartigue, L.; Hugounenq, P.; Alloyeau, D.; Clarke, S. P.; Levy, M.;Bacri, J.-C.; Bazzi, R.; Brougham, D. F.; Wilhelm, C.; Gazeau, F.Cooperative Organization in Iron Oxide Multi-Core NanoparticlesPotentiates Their Efficiency as Heating Mediators and MRI ContrastAgents. ACS Nano 2012, 6, 10935−10949.(10) Roch, A.; Muller, R. N.; Gillis, P. Theory of Proton RelaxationInduced by Superparamagnetic Particles. J. Chem. Phys. 1999, 110,5403−5411.(11) Mejías, R.; Perez-Yague, S.; Gutierrez, L.; Cabrera, L. I.; Spada,R.; Acedo, P.; Serna, C. J.; Lazaro, F. J.; Villanueva, A.; Morales, M. P.;et al. Dimercaptosuccinic Acid-Coated Magnetite Nanoparticles forMagnetically Guided in Vivo Delivery of Interferon Gamma forCancer Immunotherapy. Biomaterials 2011, 32, 2938−2952.(12) Majeed, M. I.; Lu, Q.; Yan, W.; Li, Z.; Hussain, I.; Tahir, M. N.;Tremel, W.; Tan, B. Highly Water-Soluble Magnetic Iron Oxide(Fe3O4) Nanoparticles for Drug Delivery: Enhanced in VitroTherapeutic Efficacy of Doxorubicin and MION Conjugates. J.Mater. Chem. B 2013, 1, 2874−2884.(13) Johannsen, M.; Gneveckow, U.; Eckelt, L.; Feussner, A.;Waldofner, N.; Scholz, R.; Deger, S.; Wust, P.; Loening, S. A.; Jordan,A. Clinical Hyperthermia of Prostate Cancer Using MagneticNanoparticles: Presentation of a New Interstitial Technique. Int. J.Hyperthermia 2005, 21, 637−647.

(14) Maier-Hauff, K.; Ulrich, F.; Nestler, D.; Niehoff, H.; Wust, P.;Thiesen, B.; Orawa, H.; Budach, V.; Jordan, A. Efficacy and Safety ofIntratumoral Thermotherapy Using Magnetic Iron-Oxide Nano-particles Combined with External Beam Radiotherapy on Patientswith Recurrent Glioblastoma Multiforme. J. Neurooncol. 2011, 103,317−324.(15) Lee, J.-H.; Jang, J.-T.; Choi, J.-S.; Moon, S. H.; Noh, S.-H.; Kim,J.-W.; Kim, J.-G.; Kim, I.-S.; Park, K. I.; Cheon, J. Exchange-CoupledMagnetic Nanoparticles for Efficient Heat Induction. Nat. Nanotechnol.2011, 6, 418−422.(16) Huang, H.; Delikanli, S.; Zeng, H.; Ferkey, D. M.; Pralle, A.Remote Control of Ion Channels and Neurons Through Magnetic-Field Heating of Nanoparticles. Nat. Nanotechnol. 2010, 5, 602−606.(17) Jordan, A.; Wust, P.; Fahling, H.; John, W.; Hinz, A.; Felix, R.Inductive Heating of Ferrimagnetic Particles and Magnetic Fluids:Physical Evaluation of Their Potential for Hyperthermia. Int. J.Hyperthermia 1993, 9, 51−68.(18) Demortiere, A.; Panissod, P.; Pichon, B. P.; Pourroy, G.;Guillon, D.; Donnio, B.; Begin-Colin, S. Size-Dependent Properties ofMagnetic Iron Oxide Nanocrystals. Nanoscale 2011, 3, 225−232.(19) Brezovich, I. A. Low Frequency Hyperthermia. Med. Phys.Monogr. 1988, 16, 82−111.(20) Park, J.; An, K.; Hwang, Y.; Park, J.-G.; Noh, H.-J.; Kim, J.-Y.;Park, J.-H.; Hwang, N.-M.; Hyeon, T. Ultra-Large-Scale Syntheses ofMonodisperse Nanocrystals. Nat. Mater. 2004, 3, 891−895.(21) Sun, S.; Zeng, H.; Robinson, D. B.; Raoux, S.; Rice, P. M.;Wang, S. X.; Li, G. Monodisperse MFe2O4 (M = Fe, Co, Mn)Nanoparticles. J. Am. Chem. Soc. 2003, 126, 273−279.(22) Salafranca, J.; Gazquez, J.; Perez, N.; Labarta, A.; Pantelides, S.T.; Pennycook, S. J.; Batlle, X.; Varela, M. Surfactant OrganicMolecules Restore Magnetism in Metal-Oxide Nanoparticle Surfaces.Nano Lett. 2012, 12, 2499−2503.(23) Salas, G.; Casado, C.; Teran, F. J.; Miranda, R.; Serna, C. J.;Morales, M. P. Controlled Synthesis of Uniform Magnetite Nano-crystals with High-Quality Properties for Biomedical Applications. J.Mater. Chem. 2012, 22, 21065−21075.(24) Wetterskog, E.; Tai, C. W.; Grins, J.; Bergstrom, L.; Salazar-Alvarez, G. Anomalous Magnetic Properties of Nanoparticles Arisingfrom Defect Structures: Topotaxial Oxidation of Fe1‑xO|Fe3‑δO4 Core|Shell Nanocubes to Single-Phase Particles. ACS Nano 2013, 7, 7132−7144.(25) Serantes, D.; Simeonidis, K.; Angelakeris, M.; Chubykalo-Fesenko, O.; Marciello, M.; Morales, M. P.; Baldomir, D.; Martinez-Boubeta, C. Multiplying Magnetic Hyperthermia Response byNanoparticle Assembling. J. Phys. Chem. C 2014, 118, 5927−5934.(26) Martinez-Boubeta, C.; Simeonidis, K.; Serantes, D.; Conde-Leboran, I.; Kazakis, I.; Stefanou, G.; Pena, L.; Galceran, R.; Balcells,L.; Monty, C.; et al. Adjustable Hyperthermia Response of Self-Assembled Ferromagnetic Fe-MgO Core−Shell Nanoparticles byTuning Dipole−Dipole Interactions. Adv. Funct. Mater. 2012, 22,3737−3744.(27) Martinez-Boubeta, C.; Simeonidis, K.; Makridis, A.; Angelakeris,M.; Iglesias, O.; Guardia, P.; Cabot, A.; Yedra, L.; Estrade, S.; Peiro, F.;et al. Learning from Nature to Improve the Heat Generation of Iron-Oxide Nanoparticles for Magnetic Hyperthermia Applications. Sci. Rep.2013, 3, 1652.(28) Landi, G. T. Role of Dipolar Interaction in MagneticHyperthermia. Phys. Rev. B 2014, 89, 014403.(29) Levy, M.; Gazeau, F.; Bacri, J. C.; Wilhelm, C.; Devaud, M.Modeling Magnetic Nanoparticle Dipole-Dipole Interactions InsideLiving Cells. Phys. Rev. B 2011, 84, 075480.(30) Levy, M.; Wilhelm, C.; Devaud, M.; Levitz, P.; Gazeau, F. HowCellular Processing of Superparamagnetic Nanoparticles Affects TheirMagnetic Behavior and NMR Relaxivity. Contrast Media Mol. Imaging2012, 7, 373−383.(31) Di Corato, R.; Espinosa, A.; Lartigue, L.; Tharaud, M.; Chat, S.;Pellegrino, T.; Menager, C.; Gazeau, F.; Wilhelm, C. MagneticHyperthermia Efficiency in the Cellular Environment for DifferentNanoparticle Designs. Biomaterials 2014, 35, 6400.



(32) Rosensweig, R. E. Heating Magnetic Fluid with AlternatingMagnetic Field. J. Magn. Magn. Mater. 2002, 252, 370−374.(33) Simeonidis, K.; Martinez-Boubeta, C.; Balcells, L.; Monty, C.;Stavropoulos, G.; Mitrakas, M.; Matsakidou, A.; Vourlias, G.;Angelakeris, M. Fe-Based Nanoparticles as Tunable Magnetic ParticleHyperthermia Agents. J. Appl. Phys. 2013, 114, 103904.(34) Fortin, J. P.; Wilhelm, C.; Servais, J.; Menager, C.; Bacri, J. C.;Gazeau, F. Size-Sorted Anionic Iron Oxide Nanomagnets as ColloidalMediators for Magnetic Hyperthermia. J. Am. Chem. Soc. 2007, 129,2628−2635.(35) Usov, N. A.; Liubimov, B. Ya. Dynamics of MagneticNanoparticle in a Viscous Liquid: Application to Magnetic Nano-particle Hyperthermia. J. Appl. Phys. 2012, 112, 023901.(36) Villanueva, A.; Canete, M.; Roca, A. G.; Calero, M.;Veintemillas-Verdaguer, S.; Serna, C. J.; Morales, M. P.; Miranda, R.The Influence of Surface Functionalization on the EnhancedInternalization of Magnetic Nanoparticles in Cancer Cells. Nano-technology 2009, 20, 115103.(37) Mehdaoui, B.; Carrey, J.; Stadler, M.; Cornejo, A.; Nayral, C.;Delpech, F.; Chaudret, B.; Respaud, M. Influence of a TransverseStatic Magnetic Field on the Magnetic Hyperthermia Properties andHigh-Frequency Hysteresis Loops of Ferromagnetic FeCo Nano-particles. Appl. Phys. Lett. 2012, 100, 052403.(38) Teran, F. J.; Casado, C.; Mikuszeit, N.; Salas, G.; Bollero, A.;Morales, M. P.; Camarero, J.; Miranda, R. Accurate Determination ofthe Specific Absorption Rate in Superparamagnetic NanoparticlesUnder Non-Adiabatic Conditions. Appl. Phys. Lett. 2012, 101, 062413.(39) Santoyo Salazar, J.; Perez, L.; de Abril, O.; Truong Phuoc, L.;Ihiawakrim, D.; Vazquez, M.; Greneche, J.-M.; Begin-Colin, S.;Pourroy, G. Magnetic Iron Oxide Nanoparticles in 10−40 nmRange: Composition in Terms of Magnetite/Maghemite Ratio andEffect on the Magnetic Properties. Chem. Mater. 2011, 23, 1379−1386.(40) Martínez-Boubeta, C.; Simeonidis, K.; Angelakeris, M.; Pazos-Perez, N.; Giersig, M.; Delimitis, A.; Nalbandian, L.; Alexandrakis, V.;Niarchos, D. Critical Radius for Exchange Bias in Naturally OxidizedFe Nanoparticles. Phys. Rev. B 2006, 74, 054430.(41) Morales, M. P.; Veintemillas-Verdaguer, S.; Montero, M. I.;Serna, C. J.; Roig, A.; Casas, L.; Martínez, B.; Sandiumenge, F. Surfaceand Internal Spin Canting in γ-Fe2O3 Nanoparticles. Chem. Mater.1999, 11, 3058−3064.(42) Cornell, R. M. The Iron Oxides. Structure, Properties, Reactions,Occurrences and Uses, 2nd ed.; Schwertmann, U., Ed.; Wiley-VCH:Weinheim, Germany, 2003.(43) Hansen, M. F.; Mørup, S. Estimation of Blocking Temperaturesfrom ZFC/FC Curves. J. Magn. Magn. Mater. 1999, 203, 214−216.(44) Mehdaoui, B.; Meffre, A.; Carrey, J.; Lachaize, S.; Lacroix, L.-M.;Gougeon, M.; Chaudret, B.; Respaud, M. Optimal Size of Nano-particles for Magnetic Hyperthermia: A Combined Theoretical andExperimental Study. Adv. Funct. Mater. 2011, 21, 4573−4581.(45) Hergt, R.; Dutz, S.; Roder, M. Effects of Size Distribution onHysteresis Losses of Magnetic Nanoparticles for Hyperthermia. J.Phys.: Condens. Matter 2008, 20, 385214.(46) Kallumadil, M.; Tada, M.; Nakagawa, T.; Abe, M.; Southern, P.;Pankhurst, Q. A. Suitability of Commercial Colloids for MagneticHyperthermia. J. Magn. Magn. Mater. 2009, 321, 1509−1513.(47) Carrey, J.; Mehdaoui, B.; Respaud, M. Simple Models forDynamic Hysteresis Loop Calculations of Magnetic Single-DomainNanoparticles: Application to Magnetic Hyperthermia Optimization. J.Appl. Phys. 2011, 109, 083921.(48) Mehdaoui, B.; Tan, R. P.; Meffre, A.; Carrey, J.; Lachaize, S.;Chaudret, B.; Respaud, M. Increase of Magnetic HyperthermiaEfficiency Due to Dipolar Interactions in Low-Anisotropy MagneticNanoparticles: Theoretical and Experimental Results. Phys. Rev. B2013, 87, 174419.(49) Poperechny, I. S.; Raikher, Yu. L.; Stepanov, V. I. DynamicMagnetic Hysteresis in Single-Domain Particles with UniaxialAnisotropy. Phys. Rev. B 2010, 82, 174423.(50) Chantrell, R. W.; Wohlfarth, E. P. Dynamic and Static Propertiesof Interacting Fine Ferromagnetic Particles. J. Magn. Magn. Mater.

1983, 40, 1−11. Shtrikman, S.; Wohlfarth, E. P. The Theory of theVogel-Fulcher Law of Spin Glasses. Phys. Lett. A 1981, 85, 467−470.(51) Victoria, R. H. Predicted Time Dependence of the SwitchingField for Magnetic Materials. Phys. Rev. Lett. 1989, 63, 457−460.



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