Modulation of Magnetic Heating via Dipolar Magnetic Interactions in

Article pubs.acs.org/JPCC

Modulation of Magnetic Heating via Dipolar Magnetic Interactions in Monodisperse and Crystalline Iron Oxide Nanoparticles Gorka Salas,†,‡ Julio Camarero,†,§ David Cabrera,† Hélène Takacs,†,‡ María Varela,∥,⊥ Robert Ludwig,# Heidi Daḧ ring,# Ingrid Hilger,# Rodolfo Miranda,†,§ María del Puerto Morales,‡ and Francisco José Teran*,†,% †

IMDEA Nanociencia, Campus Universitario de Cantoblanco, 28049 Madrid, Spain Instituto de Ciencia de Materiales de Madrid-CSIC, C\Sor Juana Inés de la Cruz, 5 Campus Universitario de Cantoblanco, 28049 Madrid, Spain § Dpt. Física de la Materia Condensada and Instituto Nicolas Cabrera, Universidad Autónoma de Madrid, Campus Universitario de Cantoblanco, 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 exposure mediated by magnetic nanoparticles, we provide new guidelines for tailoring magnetic relaxation processes via dipolar interactions. For this purpose, highly crystalline and monodisperse magnetic iron oxide nanocrystals whose sizes range from 7 to 22 nm were synthesized by thermal decomposition of iron organic precursors in 1-octadecene. The as-synthesized nanoparticles are soft nanomagnets, showing superparamagnetic-like behavior and SAR values which progressively increase with particle size, field frequency, and amplitude up to 3.6 kW/gFe. Our data show the influence of media viscosity, particle size, and concentration on dipolar interactions and consequently on the magnetic relaxation processes related to the heat release. Understanding the role of dipolar interactions is of great importance toward the use of iron oxide nanoparticles as efficient hyperthermia mediators. thanks to the progress in materials science4,5,17 for producing biocompatible nanoparticles with optimal magnetic properties18 and in cell biology for assessing the biological activity of IONP.2,7,8 Nowadays, IONP have a great potential as a minimally invasive and local heating generators13−15 under alternating magnetic fields (HAC) at moderate frequencies ( f) and amplitudes (μ0H) in order to preserve patient comfort and safety.19 The forthcoming clinical potential of heating mediated by IONP relies on three aspects. First, the heat release should be the highest possible at the lowest IONP dose. Second, uniform size and morphology are required to provide homogeneous heat dissipation power according to each

1. INTRODUCTION Iron oxide nanoparticles (IONP) are finding a rapidly increasing number and variety of biomedical applications1,2 due to their size-driven colloidal and magnetic properties at the nanoscale.3−5 The precise control of IONP size and coating engineering6 favor their internalization into cells without cytotoxicity drawbacks.7,8 These features render IONP as a suitable platform for simultaneously acting as imaging contrast agents,9,10 drug-delivery nanocarriers,11,12 and intracellular hyperthermia mediators.9,13−15 For the latter application, the conversion of electromagnetic energy into heat taking place in iron oxide nanocrystals has proven to successfully remove tumors13−15 and/or control cellular machinery.16 In the past 20 years, the use of magnetic heating mediated by IONP for therapeutic purposes has experienced a vast development. IONP have eventually reached clinical trials13,14 © 2014 American Chemical Society

Received: April 28, 2014 Revised: July 23, 2014 Published: July 23, 2014 19985

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

The Journal of Physical Chemistry C

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

IONP dose. Third, heating mechanisms should not be influenced by the biological matrix (i.e., cells or tissues where IONP are located) in terms of viscosity and aggregation. Any improvement in the chemical synthesis of IONP to strengthen their magnetothermal properties and to control their heat loss mechanisms is of paramount relevance for their application as magnetic heating mediators. In order to achieve these goals, big efforts are paid to obtain highly crystalline and narrow size distribution IONP with large saturation magnetization values (MS). Thermal decomposition routes20,21 allow to obtain crystalline IONP22 due to the high temperature of the chemical reaction which favor both crystal growth and size distribution narrowing, leading to high values of MS and heating efficiency.23,24 Recent strategies to enhance MS and heating efficiency are based on manipulation of the exchange coupling in core−shell nanoparticles15 or cooperative phenomena.9,25−27 The latter strategy takes advantage of the collective nanoparticle behavior mediated by magnetic dipolar interactions, which enhance the heat efficiency under certain conditions.9,25,27,28 Understanding the role of dipolar interactions is highly crucial for the application of magnetic nanoparticles in biomedicine.26,27 After cell uptake, IONP are located inside subcellular vesicles forming large aggregates29,30 where interparticle interactions negatively influence their magnetic properties,29and consequently their contrast signal30 and/or heating efficiency.31 A precise control of the heat exposure is mandatory for the clinical translation of magnetic heating mediated by IONP. This condition is met when the nature of heating mechanisms remains invariable under distinct environmental conditions such as viscosity or aggregation. Different magnetic relaxation processes govern heat dissipation in magnetic nanoparticles32,33 depending on distinct parameters such as particle size, dispersion media viscosity, and magnetic properties. In the case of superparamagnetic IONP, magnetic moment relaxation mechanisms involved in heat dissipation can be described in terms of Brown and Néel processes.34 These relaxation processes are related to different physical phenomena. On one hand, Brown relaxation is due to thermally driven reorientation (i.e., physical rotation of the particle) in the dispersion media while the magnetic moment is locked onto the crystal anisotropy axis. On the other hand, Néel relaxation is related to the internal reorientation of the particle magnetic moment due to thermal fluctuations across the anisotropic barrier of the particle magnetic moment. Néel magnetic relaxation processes depend on particle volume (V), temperature (T), and effective magnetic anisotropy (Keff), while Brown relaxation processes depend on hydrodynamic volume, dispersion media viscosity (η), and T. In general, both relaxation processes coexist until one of them shows smaller relaxation rates and then dominates. Typically, heating mechanisms evolve from Néel to Brown processes when increasing size and Keff.34 However, Néel relaxation processes are favored when the field amplitude is larger than the anisotropy field.35 Here, we report on the study of the magnetothermal properties of highly crystalline and monodisperse IONP whose core sizes range from 7 to 22 nm. IONP were synthesized by thermal decomposition method previously reported.23 The studied IONP are highly uniform in size and morphology, showing extremely good crystalline features. In addition, IONP show superparamagnetic-like behavior with MS values around 70 emu/gmagh and specific absorption rate (SAR) values of

2. MATERIALS AND METHODS Synthesis of Magnetic Iron Oxide Nanoparticles. IONP with core size of 7 nm were synthesized by thermal decomposition of Fe(acac)3 following Sun’s method,21 but with mechanical stirring instead of magnetic stirring, using 1,2dodecanediol instead of 1,2-hexadecanediol and with 1octadecene as solvent. IONP of larger sizes from 12 to 22 nm were synthesized by a thermal decomposition of Fe(oleate)3 described by Park et al.20 but including some modifications.23 The resulting hydrophobic IONP were subsequently transferred to aqueous media after a ligand substitution 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 keV microscopes JEOL JEM 2000 FXII and JEOL JEM 2100. Samples were prepared by placing one drop of a dilute suspension of the hydrophobic particles in hexane onto a carbon-coated copper grid and leaving it to dry at room temperature. The size distributions were determined through manual analysis of ensembles of over 300 particles found in randomly selected areas of the enlarged micrographs, with ImageTool software (UTHSCSA) to obtain the mean size and standard deviation. Atomic resolution scanning TEM images were acquired in a Nion UltraSTEM200 equipped with a spherical aberration fifth-order corrector and a Gatan Enfinium EEL spectrometer. A Nion UltraSTEM100 operated at 60 kV and equipped with a Nion aberration corrector and a Gatan Enfina spectrometer was also used. Colloidal Characterization and Hydrodynamic Size Variation. The ligand substitution process allows to transfer the synthesized IONP to aqueous dispersions with some degree of IONP aggregation. Thus, dynamic light scattering (DLS) was employed to measure such aggregation degree expressed by the hydrodynamic size (DH). A Malvern Zetasizer Nano ZS90 was employed for measuring DH in the studied IONP in dilute particle water suspensions (260−300

13.5 5.3 4.8 2.9−3.4 1.6−1.9

2.43 4.83 6.90 8.9−10.4 8.9−10.6

0.06 0.21 0.82 1.61 4.16 (7.03)c

0.04 0.13 0.52 1.02 2.60 (6.87)c

7 12 14 18 22 a

1 1 1 2 2

Values 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.

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 SAR size dependence at given HAC conditions.44 In addition, the heat losses per cycle (SAR/f)45 is related to the area of hysteresis loops. It reaches values up to 4.16 J/kgFe for d0 = 22 nm, revealing a remarkable sensitivity (up to 1000-fold) of the opening of magnetization cycles for increasing sizes at moderate 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 heating efficiencies obtained under different HAC conditions.46 ILP is given by the expression ILP = SAR/f H2, where f and H are the applied field frequency and amplitude, respectively. The conversion of SAR into ILP values has a proper meaning within the limits of linear response theory (i.e., when maximum

Figure 4. Magnetic field amplitude and size dependence of SAR and SAR/f obtained for IONP dispersed in water at given IONP concentration (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 IONP concentration 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). 19989



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Figure 6. Magnetic field amplitude dependence of SAR values obtained for d0 = 22 nm dispersed in water (black color) and agar (red color), f = 104 kHz 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 in water and agar dispersions for d0 = 22 nm with iron content of 2.5 mgFe/mL.

applied field amplitude is much smaller than magnetic field at which the magnetization saturates).47 As observed in Figure 3a, a MS value is reached for all IONP sizes beyond 1 T. Thus, the HAC conditions employed in this work ( f ≤ 435 kHz and μ0H ≤ 50 mT) fit within the limits of the linear response theory for all IONP studied. Kallumadil et al.46 show that particles with ILP values beyond 1 are good candidates as hyperthermia mediators. ILP values of the studied IONP range from 0 up to 8.15 depending on d0, dispersion viscosity, and field conditions as shown in Table 1. At moderate conditions, the maximal ILP values are 2.60 nH m2/kgFe for d0 = 22 nm. However, under extreme HAC conditions (435 kHz and 40 mT), the maximal ILP 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 nanoparticles are typically related to Néel and Brown relaxation processes.32 Calorimetry measurements allow to distinguish among both relaxation processes when varying the viscosity of the IONP dispersion because it affects particle rotation.34 Therefore, one expects to observe differences in the heat release from free-standing and immobilized IONP. Particle Size Effects on Magnetic Relaxation Processes. In order to assess the influence of η on heat dissipation power, we have measured SAR values for IONP with different sizes and iron content. IONP were dispersed in water, where particles are ideally free, forming a stable colloids and agar, where particles are ideally immobilized. Figure 5 shows SAR values obtained in water (SARwater) and agar (SARagar) for IONP with d0 ranging from 14 up to 22 nm under moderate HAC conditions and a given iron content (10 mgFe/mL). The SAR field dependence vary with particle size observing a linear field behavior at d0 = 14 nm while at d0 = 22 nm the field dependence is parabolic-like. Such distinct field evolution with size is understood in terms of the Stoner−Wolfhart model where anisotropy field is a crucial parameter defining the SAR field dependence.31,44 In addition, the maximal SAR values significantly increase with size as shown in Figure 5. Simultaneously, comparable SAR values at any field amplitude are observed for IONP dispersed in water (black circles) and agar (red circles) with sizes d0 = 14 and 18 nm. This indicates that heating mechanisms are not significantly influenced by viscosity, which is a clear indication of Néel relaxation processes.32,34 However, SAR values significantly differ in water and agar dispersions for d0 = 22 nm, reflecting the influence of viscosity on the heat released from the largest IONP when μ0H > 10 mT. Indeed, SAR values in agar

progressively decrease (up to 70%) with respect to the values measured in water dispersions, being larger in water. The SAR variation related the viscosity increase (ΔSARvis) is better appreciated by using the following expression: ΔSAR vis = 100 ×

SAR water − SAR agar SAR water

(2)

Figure 5d shows the values of ΔSARvis derived from data corresponding to different d0 at μ0H = 50 mT shown in Figures 5a−c. Interestingly, these results reveal the correlation between ΔSARvis and particle core size when observing the rapid increase of values beyond d0 = 18 nm. At first glance, we may consider that Brown relaxation is the dominant heating mechanism for d0 = 22 nm due to the observed SAR viscosity dependence. However, it is worth noting the SARagar reduction at 50 mT for d0 = 22 nm (70 W/gFe) with respect to the values at d0 = 14 nm (73 W/gFe) and d0 = 18 nm (149 W/gFe). These results do not match the behavior of SARwater at μ0H = 50 mT, which continuously increases with size. Recent works show that particle interactions strongly modify SAR values leading to significant reductions or enhancements depending on the nature of the particle interactions.9,25−28 The increase of particle concentration favors dipolar magnetic interactions, leading to significantly modification of their magnetic relaxation processes and consequently their heat dissipation power. Recently, it has been shown that SAR can be influenced by viscosity due to other mechanisms different than Néel−Brown relaxation rate crossover.25,28 Indeed, the misalignment between easy-axis and particle magnetization directions may alter magnetic dipolar interactions,25 resulting in a reduction of heating efficiency. Interaction Effects on Magnetic Relaxation Processes. In order to determine the influence of particle interactions on heat dissipation mediated by IONP of d0 = 22 nm, we have studied the SAR field dependences for two IONP concentrations (2.5 and 10 mgFe/mL) in water and agar dispersions at 104 kHz. Figure 6 shows SAR values obtained in water (black circles) and agar (red circles) for 2.5 and 10 mgFe/mL iron contents. First, SARwater and SARagar values are comparable at low iron concentration (i.e., 2.5 mgFe/mL) in the overall field range, even at the highest frequency (see inset of Figure 6a). SARagar values are slightly larger than SARwater which can be understood in terms of the loss susceptibility for noninteracting particles dispersed in media with different viscosity.32 Second, at high IONP concentration (i.e., 10 mgFe/mL), SARwater values 19990



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are up to 3 times larger than SARagar. Thus, one can appreciate that ΔSARvis values are negligible at low iron content but around 70% at high IONP concentration. Besides, SARagar values at 50 mT show a 50% reduction when increasing iron content, contrary to the 100% increased of the SARwater values. According to the fact that SAR = Af, where A is the area of the hysteresis loop43,47−49 when Néel relaxation prevails and the SAR data shown in Figures 6a,b, one may expect the different magnetization loops when IONP are dispersed in water or agar at different iron contents. Figure 7 shows the IONP massFigure 8. DH dependence of SAR values obtained for d0 = 12 and 22 nm particles dispersed in agar with similar IONP concentration (2.5 mgFe/mL) at f = 104 kHz and 40 mT.

(∼50%). This may imply that such SARagar reduction is related to the increase of the number of interacting particles into the colloidal aggregate of larger DH. Furthermore, we can extract two other important messages from Figure 8. First, interacting phenomena become important with particle size according to the increase of the magnetic moment per particle.40 This is in agreement with the results shown in Figures 5c and 6b. Second, the IONP dispersion viscosity influences the intra-aggregate dipolar interactions. Indeed, the heat dissipated from IONP is originated by irreversible magnetization jumps favored by thermal fluctuations across an energy barrier separating minima.28 The heating release is associated with the number of jumps occurring due to thermal fluctuations, although the height of the energy barrier is also relevant. For low-energy barriers or high temperatures, the number of magnetization jumps related to thermal fluctuations of magnetic moments of the nanoparticle ensembles is high, but the heat conversion is small. However, when barriers are high, the number of particle magnetic moment relaxation processes is reduced but the heat conversion is higher. The energy barrier across which thermal fluctuations occur generally correspond to the anisotropy energy barrier for noninteracting particles.50 However, this energy barrier is notably influenced by magnetic dipolar interactions25,26,28 and field amplitude.51 Then, any variation of the energetic barrier related to interacting phenomena significantly alter IONP magnetic moment relaxation processes under dynamical field conditions and consequently the related heat dissipation.47 In our particular case, IONP whose sizes are smaller than 22 nm show nonsignificant influence of dipolar interactions on their SAR values (see Figure 5). However, interacting effects are significantly appreciated when increasing iron content for 22 nm size IONP. Figure 9 shows the

Figure 7. Iron mass-normalized magnetization cycles of 22 nm size IONP dispersed in water (black color) and agar (red color) at f = 104 kHz 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 size IONP dispersed in water and agar at f = 104 kHz and 40 mT at two IONP concentrations (2.5 and 10 mgFe/mL).

normalized hysteresis loops of the 22 nm IONP dispersed in water 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 of dispersion media, in agreement with SAR values (see Figures 7c,d). However, the area A of hysteresis loops significantly increases in water when increasing iron content whereas it decreases in agar dispersion (see Figure 7b). The shape of the magnetization loops provides some additional information. The shape of magnetization loops varies with IONP concentration and viscosity being more elliptical in agar than in water. Such elliptical shape becomes more pronounced when increasing IONP concentration. This shape is typical from IONP with randomly oriented anisotropy axis with respect to the external field direction.48,49 In order to determine the role of interparticle interactions in such experimental results, we consider the influence of aggregate size and particle concentration 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 iron content (2.5 mgFe/mL) and HAC conditions ( f = 104 kHz and 50 mT). At first glance, a clear SARagar reduction is observed for both particle sizes when DH is increased 3 times. Such reduction is more pronounced for the largest particles, where SARagar values diminish more than 30% for d0 = 22 nm in comparison with the 15% reduction for d0 = 12 nm. Interestingly, the SARagar reduction when DH is increased for d0 = 22 nm (33%) is comparable to the one observed in Figure 6 when increasing iron content from 2.5 to 10 mgFe/mL

Figure 9. IONP concentration dependence of SAR values obtained in water dispersions for d0 = 22 nm at f = 104 kHz and 40 mT. 19991



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various biomedical applications as recently shown.29−31 Indeed, IONP inside subcellular vesicles form large aggregates that favor particle interactions. Our results underline the role of particle size, concentration, and dispersion viscosity in magnetic dipolar interactions for modulating IONP magnetic relaxation processes and consequently their heat dissipation. We have shown that monodisperse and crystalline IONP constitute a suitable platform for acting as efficient intracellular heating mediators. Further theoretical models are needed to describe how the dipolar interactions influence SAR and how interaction phenomena depend on particle size, viscosity, and HAC conditions.

evolution of SAR values when increasing iron content in water IONP dispersions under given HAC conditions (104 kHz and 40 mT). Initially, SARwater values remain constant at low IONP concentration range. Beyond 2 mgFe/mL, SARwater progressively increases with iron content doubling at the highest IONP concentration (10 mgFe/mL) the value observed at the lowest concentration (0.3 mgFe/mL). Such behavior can be understood as due to variations in the frequency of magnetic relaxation events and the related heat conversion as the dipolar interactions take place. At low IONP concentrations, the energy barrier is small (i.e., magnetic field-normalized anisotropy barrier), leading to a large number of magnetic relaxation 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 of the number of magnetic relaxation events but involves a higher heat release.26,28 Thus, we can understand the results about the evolution of SARwater and area A with IONP concentration in terms of the interacting phenomena described by MartinezBoubeta et al.26 Nevertheless, understanding the reduction of SARagar and area A values with iron content may imply a different scenario. At low iron content, heat dissipation power in agar is related to the out-of-phase magnetic susceptibility which can be derived from Néel relaxation rate for noninteracting superparamagnets.32 At high iron content, dipolar magnetic interactions are significantly active as shown in Figure 9, influencing magnetic relaxation processes. Recent works25,28 show that dipolar interactions between IONP with soft magnetic properties (i.e., low magnetic anisotropy values) may favor chain formation. Under such conditions, dipolar interactions are highly sensitive to particle mobility what strongly influence their heating efficiency. As mentioned above, IONP dispersed in agar behave as nanomagnets with randomly oriented anisotropy axis with respect to the external field direction or particle magnetization vector. The angle (θ) between easy-axis and magnetization vector is therefore finite in agar dispersions where IONP are immobilized. On the contrary, IONP dispersed in water where particles are free to rotate favoring the aligment between easy-axis and magnetization vector (i.e., θ = 0). Magnetization cycles show more pronounced square shape when θ is closer to zero, as observed in Figure 7b. Interacting particles with θ = 0 form chains driving a collective behavior that benefits their heating efficiency9,25,27 while the increase of θ values leads to the reduction of the hysteretic area25 and the heating efficiency. In our case, we discard the possibility of chain formation for the 22 nm size IONP in water at high concentration because their high colloidal stability and the MR is negligible. However, we expect that heating efficiency shall benefit from the θ reduction observed for IONP dispersed in water. In that case, SAR values should be larger with respect to immobilized particles in agar where θ value should be larger, and therefore SAR values should decrease as shown in Figure 6b. This is in agreement with the evolution of area A and the magnetization shape observed in Figure 7b. In summary, we observe that magnetic interactions favor/affect the easy axis alignment with the particle 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 importance toward controlling the heat exposure supplied by IONP as intracellular hyperthermia mediators. Cellular processing of nanoparticles influences their physical properties at the root of

4. CONCLUSIONS In this work, we have performed magnetic and calorimetry studies on highly crystalline and monodisperse IONP synthesized by thermal decomposition. We have shown the superparamagnetic-like behavior near to room temperatures for all particle sizes. SAR values progressively increase with particle size, field frequency, and amplitude up to 3.6 kW/gFe. In general, magnetic relaxation processes are dominated by the Néel process for all IONP sizes. However, beyond d0 = 18 nm dipolar interactions are strongly relevant and heating efficiency varies with viscosity. The observation of large SAR values related to Néel relaxation process in monodisperse and highly crystalline IONP reflects the suitability of thermal decomposition route for providing highly efficient magnetic heating mediators. Our data show the influence of media viscosity, particle size, and concentration on dipolar interactions and consequently on the magnetic relaxation processes related to the heat release. For that purpose, further theoretical works are required to describe the influence of dipolar magnetic interactions on IONP heat dissipation as a function of particle size, dispersion viscosity, and field conditions.

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ASSOCIATED CONTENT

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AUTHOR INFORMATION

S Supporting Information *

Zero field cooling and field cooling magnetization measurements for IONP of different sizes; maghemite mass-normalized magnetization cycles for IONP dispersed in water and agar. This material is available free of charge via the Internet at http://pubs.acs.org. Corresponding Author

*E-mail: [email protected] (F.J.T.). Present Address

H.T.: Commissariat de l’Energie Atomique, LETI, Campus MINATEC, 17, avenue des Martyrs 38054 Grenoble Cedex 9, France. Author Contributions

G.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., and F.J.T. performed the experiments; G.S., M.P.M., and F.J.T. cowrote the paper. All authors discussed the results and commented on the manuscript. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work has been partially supported by European Commission (MULTIFUN, no. 262943), Spanish Ministry of 19992



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(14) Maier-Hauff, K.; Ulrich, F.; Nestler, D.; Niehoff, H.; Wust, P.; Thiesen, B.; Orawa, H.; Budach, V.; Jordan, A. Efficacy and Safety of Intratumoral Thermotherapy Using Magnetic Iron-Oxide Nanoparticles Combined with External Beam Radiotherapy on Patients with 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-Coupled Magnetic 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 MagneticField 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) Demortière, A.; Panissod, P.; Pichon, B. P.; Pourroy, G.; Guillon, D.; Donnio, B.; Bégin-Colin, S. Size-Dependent Properties of Magnetic 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 of Monodisperse 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.; Pérez, N.; Labarta, A.; Pantelides, S. T.; Pennycook, S. J.; Batlle, X.; Varela, M. Surfactant Organic Molecules 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 Nanocrystals with High-Quality Properties for Biomedical Applications. J. Mater. Chem. 2012, 22, 21065−21075. (24) Wetterskog, E.; Tai, C. W.; Grins, J.; Bergström, L.; SalazarAlvarez, G. Anomalous Magnetic Properties of Nanoparticles Arising from 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.; ChubykaloFesenko, O.; Marciello, M.; Morales, M. P.; Baldomir, D.; MartinezBoubeta, C. Multiplying Magnetic Hyperthermia Response by Nanoparticle Assembling. J. Phys. Chem. C 2014, 118, 5927−5934. (26) Martinez-Boubeta, C.; Simeonidis, K.; Serantes, D.; CondeLeborán, I.; Kazakis, I.; Stefanou, G.; Peña, L.; Galceran, R.; Balcells, L.; Monty, C.; et al. Adjustable Hyperthermia Response of SelfAssembled Ferromagnetic Fe-MgO Core−Shell Nanoparticles by Tuning 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 IronOxide Nanoparticles for Magnetic Hyperthermia Applications. Sci. Rep. 2013, 3, 1652. (28) Landi, G. T. Role of Dipolar Interaction in Magnetic Hyperthermia. Phys. Rev. B 2014, 89, 014403. (29) Lévy, M.; Gazeau, F.; Bacri, J. C.; Wilhelm, C.; Devaud, M. Modeling Magnetic Nanoparticle Dipole-Dipole Interactions Inside Living Cells. Phys. Rev. B 2011, 84, 075480. (30) Lévy, M.; Wilhelm, C.; Devaud, M.; Levitz, P.; Gazeau, F. How Cellular Processing of Superparamagnetic Nanoparticles Affects Their Magnetic Behavior and NMR Relaxivity. Contrast Media Mol. Imaging 2012, 7, 373−383. (31) Di Corato, R.; Espinosa, A.; Lartigue, L.; Tharaud, M.; Chat, S.; Pellegrino, T.; Ménager, C.; Gazeau, F.; Wilhelm, C. Magnetic Hyperthermia Efficiency in the Cellular Environment for Different Nanoparticle Designs. Biomaterials 2014, 35, 6400.

Economy and Competitiveness (MAT2010-21822-C02-01, MAT2011-23641, MAT2013-47395-C4-3-R), Madrid Regional Government (NANOBIOMAGNET, S2009/MAT-1726), and the European Research Council Starting Investigator Award STEMOX # 239739. Research at ORNL was supported by the U.S. Department of Energy (DOE), Basic Energy Sciences (BES), Materials Sciences and Engineering Division, and through a user project supported by ORNL’s Shared Research Equipment (ShaRE) User Program, which is also sponsored by DOE-BES. F.J.T. acknowledges financial support from Ramon y 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.

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REFERENCES

(1) Krishnan, K. M. Biomedical Nanomagnetics: A Spin Through Possibilities in Imaging, Diagnostics, and Therapy. IEEE Trans. Magn. 2010, 46, 2523−2558. (2) Hilger, I.; Kaiser, W. A. Iron Oxide-Based Nanostructures for MRI 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 and Magnetic Energy Storage. Chem. Soc. Rev. 2009, 38, 2532−2542. (4) Roca, A. G.; Costo, R.; Rebolledo, A. F.; Veintemillas-Verdaguer, S.; Tartaj, P.; González-Carreño, T.; Morales, M. P.; Serna, C. J. Progress in the Preparation of Magnetic Nanoparticles for Applications in Biomedicine. J. Phys. D: Appl. Phys. 2009, 42, 224002. (5) Salas, G.; Veintemillas-Verdaguer, S.; Morales, M. P. Relationship Between Physico-Chemical Properties of Magnetic Fluids and Their Heating 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 Maghemite Nanoparticles. Nanoscale 2013, 5, 11428−11437. (7) Calero, M.; Gutiérrrez, L.; Salas, G.; Luengo, Y.; Lázaro, A.; Acedo, P.; Morales, M. P.; Miranda, R.; Villanueva, A. Efficient and Safe Internalization of Magnetic Iron Oxide Nanoparticles: Two Fundamental Requirements for Biomedical Applications. Nanomedicine 2014, 10, 733−743. (8) Wilkinson, K.; Ekstrand-Hammarströ m, B.; Ahlinder, L.; Guldevall, K.; Pazik, R.; Kępiński, L.; Kvashnina, K. O.; Butorin, S. M.; Brismar, H.; Ö nfelt, B.; et al. Visualization of Custom-Tailored Iron Oxide Nanoparticles Chemistry, Uptake, and Toxicity. Nanoscale 2012, 4, 7383−7393. (9) Lartigue, L.; Hugounenq, P.; Alloyeau, D.; Clarke, S. P.; Lévy, M.; Bacri, J.-C.; Bazzi, R.; Brougham, D. F.; Wilhelm, C.; Gazeau, F. Cooperative Organization in Iron Oxide Multi-Core Nanoparticles Potentiates Their Efficiency as Heating Mediators and MRI Contrast Agents. ACS Nano 2012, 6, 10935−10949. (10) Roch, A.; Muller, R. N.; Gillis, P. Theory of Proton Relaxation Induced by Superparamagnetic Particles. J. Chem. Phys. 1999, 110, 5403−5411. (11) Mejías, R.; Pérez-Yagüe, S.; Gutiérrez, L.; Cabrera, L. I.; Spada, R.; Acedo, P.; Serna, C. J.; Lázaro, F. J.; Villanueva, Á .; Morales, M. P.; et al. Dimercaptosuccinic Acid-Coated Magnetite Nanoparticles for Magnetically Guided in Vivo Delivery of Interferon Gamma for Cancer 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 Vitro Therapeutic 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 Magnetic Nanoparticles: Presentation of a New Interstitial Technique. Int. J. Hyperthermia 2005, 21, 637−647. 19993



Article

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

(32) Rosensweig, R. E. Heating Magnetic Fluid with Alternating Magnetic 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 Particle Hyperthermia Agents. J. Appl. Phys. 2013, 114, 103904. (34) Fortin, J. P.; Wilhelm, C.; Servais, J.; Ménager, C.; Bacri, J. C.; Gazeau, F. Size-Sorted Anionic Iron Oxide Nanomagnets as Colloidal Mediators for Magnetic Hyperthermia. J. Am. Chem. Soc. 2007, 129, 2628−2635. (35) Usov, N. A.; Liubimov, B. Ya. Dynamics of Magnetic Nanoparticle in a Viscous Liquid: Application to Magnetic Nanoparticle Hyperthermia. J. Appl. Phys. 2012, 112, 023901. (36) Villanueva, A.; Cañ ete, M.; Roca, A. G.; Calero, M.; Veintemillas-Verdaguer, S.; Serna, C. J.; Morales, M. P.; Miranda, R. The Influence of Surface Functionalization on the Enhanced Internalization of Magnetic Nanoparticles in Cancer Cells. Nanotechnology 2009, 20, 115103. (37) Mehdaoui, B.; Carrey, J.; Stadler, M.; Cornejo, A.; Nayral, C.; Delpech, F.; Chaudret, B.; Respaud, M. Influence of a Transverse Static Magnetic Field on the Magnetic Hyperthermia Properties and High-Frequency Hysteresis Loops of Ferromagnetic FeCo Nanoparticles. 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 of the Specific Absorption Rate in Superparamagnetic Nanoparticles Under 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 nm Range: Composition in Terms of Magnetite/Maghemite Ratio and Effect on the Magnetic Properties. Chem. Mater. 2011, 23, 1379−1386. (40) Martínez-Boubeta, C.; Simeonidis, K.; Angelakeris, M.; PazosPérez, N.; Giersig, M.; Delimitis, A.; Nalbandian, L.; Alexandrakis, V.; Niarchos, D. Critical Radius for Exchange Bias in Naturally Oxidized Fe 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. Surface and 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 Temperatures from 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 Nanoparticles for Magnetic Hyperthermia: A Combined Theoretical and Experimental Study. Adv. Funct. Mater. 2011, 21, 4573−4581. (45) Hergt, R.; Dutz, S.; Röder, M. Effects of Size Distribution on Hysteresis 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 Magnetic Hyperthermia. J. Magn. Magn. Mater. 2009, 321, 1509−1513. (47) Carrey, J.; Mehdaoui, B.; Respaud, M. Simple Models for Dynamic Hysteresis Loop Calculations of Magnetic Single-Domain Nanoparticles: 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 Hyperthermia Efficiency Due to Dipolar Interactions in Low-Anisotropy Magnetic Nanoparticles: Theoretical and Experimental Results. Phys. Rev. B 2013, 87, 174419. (49) Poperechny, I. S.; Raikher, Yu. L.; Stepanov, V. I. Dynamic Magnetic Hysteresis in Single-Domain Particles with Uniaxial Anisotropy. Phys. Rev. B 2010, 82, 174423. (50) Chantrell, R. W.; Wohlfarth, E. P. Dynamic and Static Properties of Interacting Fine Ferromagnetic Particles. J. Magn. Magn. Mater. 19994


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