surfactant effects on the structural and magnetic properties of iron oxide nanoparticles

Surfactant Effects on the Structural and Magnetic Properties of IronOxide NanoparticlesMaria Filippousi,*,† Mavroeidis Angelakeris,‡ Maria Katsikini,‡ Eleni Paloura,‡ Ilias Efthimiopoulos,§

Yuejian Wang,§ Demetris Zamboulis,∥ and Gustaaf Van Tendeloo†

†EMAT, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium‡Department of Solid State Physics, School of Physics, Aristotle University of Thessaloniki, GR-54124, Thessaloniki, Greece§Department of Physics, Oakland University, Rochester, Michigan 48309, United States∥Laboratory of General and Inorganic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki,GR-54124 Thessaloniki, Greece

ABSTRACT: Iron oxide nanoparticles were prepared using the simplest andmost efficient chemical route, the coprecipitation, in the absence and thepresence of three different and widely used surfactants. The purpose of thisstudy is to investigate the possible influence of the different surfactants on thestructure and therefore on the magnetic properties of the iron oxidenanoparticles. Thus, different techniques were employed in order to elucidatethe composition and structure of the magnetic iron oxide nanoparticles. Bycombining transmission electron microscopy with X-ray powder diffraction andX-ray absorption fine structure measurements, we were able to determine andconfirm the crystal structure of the constituent iron oxides. The magneticproperties were investigated by measuring the hysteresis loops where thesurfactant influence on their collective magnetic behavior and subsequent ACmagnetic hyperthermia response is apparent. The results indicate that theproduced iron oxide nanoparticles may be considered as good candidates forbiomedical applications in hyperthermia treatments because of their high heating capacity exhibited under an alternatingmagnetic field, which is sufficient to provoke damage to the cancer cells.

1. INTRODUCTION

Nanoparticles, made of either inorganic or organic materials,possess many novel properties compared to their bulkcounterparts.1 For example, a typical size effect in magneticnanoparticles (MNPs) is superparamagnetism, i.e., thediscrepancy between thermal and magnetic energy whichaffects the macroscopic magnetic behavior.2 The size-depend-ent magnetic features of MNPs can be employed in variousbiomedical applications, such as magnetic resonance imagingagents in diagnosis,3 heat mediators in hyperthermia treat-ments,4 and magnetic guides in drug delivery.5,6 Theseapplications are based on the fact that MNPs have sizescomparable to that of the biological entities of interest (e.g.,viruses and proteins).7 Furthermore, the outermost surfaces ofthe MNPs can be easily modified and/or functionalizedappropriately, without sparing their ability to respond toexternal magnetic fields.Iron oxide materials are widely utilized in biomedical

techniques due to their biocompatibility.8 From the severaliron oxides that exist in nature and can be prepared in thelaboratory, magnetite (Fe3O4) and maghemite (γ-Fe2O3), aremainly considered for biomedical applications, since these twocompositions fulfill the prerequisites of (1) chemical stabilityunder physiological conditions, (2) low toxicity, and (3)

sufficiently high magnetic moments.9 Many reports havedescribed efficient synthesis routes in order to produceshape-controlled, stable, biocompatible, and monodispersediron oxide nanoparticles, whereas less effort was spent on invitro cytotoxicity.10 The most common procedures forproducing iron oxide nanoparticles include the thermaldecomposition, the microemulsion, and the coprecipitation.1

Regarding the latter, coprecipitation is a relatively simple, high-yield, and easily scalable pathway to produce magneticnanoparticles for biomedical applications. A major disadvantageof this synthesis method is the yield of a wide particle sizedistribution, which can be partially regulated by a proper choiceof surfactants.1,11

The aim of the present study is to investigate the surfactanteffects on the morphological, structural, and magnetic proper-ties of iron oxide nanoparticles produced by the coprecipitationroute.12,13 We have employed three diverse, yet widely used,surfactants, namely, the cationic cetyltrimethylammoniumbromide (CTAB) surfactant, the nonionic polyvinylpyrroli-done, K30 (PVP) surfactant, and the anionic sodium cholate

Received: April 16, 2014Revised: June 3, 2014Published: July 4, 2014

Article

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(S.C.) surfactant. These surfactants differ in terms of moleculelength, as well as polar headgroup and charge. The PVP andS.C. surfactants are water-soluble, nontoxic, and are used invarious medical applications in order to control the particlesize.14,15 CTAB is the most widely used surfactant for thesynthesis of Au nanorods; even though it controls the particlesize and shape, CTAB may be toxic to cells and tissues.16−19

We have chosen the cationic CTAB since it can interfere withthe external crystal surface of the negatively charged iron oxidenanoparticles produced during coprecipitation within analkaline pH. In addition, we have prepared a batch of ironoxide nanoparticles without any surfactant for direct compar-ison.All of the obtained iron oxide nanoparticle batches, which

were prepared with and without the use of the differentsurfactants, were characterized by transmission electronmicroscopy (TEM), X-ray diffraction (XRD), and X-rayabsorption fine structure (XAFS) spectroscopy for elucidatingtheir morphological, structural, and electronic properties,respectively. Finally, magnetic measurements performed onthe various MNP batches have probed both their macroscopicmagnetic features, as well as their hyperthermia response.

2. EXPERIMENTAL METHODS

2.1. Materials. FeSO4·7H2O, cetyltrimethylammoniumbromide, and NaOH (pellets pure) were purchased fromMerck. FeCl3·6H2O and polyvinylpyrrolidone, K30 werepurchased from Sigma-Aldrich. Sodium cholate was obtainedfrom Acros Organics. Doubly distilled water was used for allsolutions. All other materials and solvents used in the analyticalmethods were of analytical grade.2.2. Synthesis of Iron Oxide Nanoparticles. Magnetic

iron oxide nanoparticles were prepared following a simplecoprecipitation method given in the literature. Essentially fourdifferent variations were implemented to synthesize tunablemagnetic iron oxide nanoparticles. In the first one 0.656 g ofCTAB and 2.0 mmol of FeCl3·6H2O were dissolved in 30 mLof doubly distilled water in a 50 mL conical flask at roomtemperature. Then 1.0 mmol FeSO4·7H2O was added to thesolution. Five millilters of a 5 N NaOH solution was addedunder stirring. A black precipitate appeared immediately.Exactly the same procedure was also followed for the othermethods, but instead of CTAB as surfactant were used 0.2 g ofS.C. chosen as a biocompatible surfactant, 0.2 g ofpolyvinylpyrrolidone, K30 and finally, no surfactant at all.The iron oxide nanoparticles were prepared via the following

reaction equation:

+ + → ↓ ++ + −Fe 2Fe 8OH Fe O 4H O2 33 4 2

The resulting precipitate of iron oxide nanoparticles wasstirred for another 20 min in the conical flask with a magneticstirrer. The resulting black precipitates were collected bycentrifugation, washed several times with double distilled water,and finally dried in a freeze-dryer.2.3. Characterization. Samples suitable for transmission

electron microscopy were prepared by drop casting the aqueoussolution containing the particles on holey, carbon-coatedcopper grids. Transmission electron microscopy, high reso-lution TEM (HRTEM) images, and selected area electrondiffraction (SAED) patterns were acquired using a Tecnai G2electron microscope operated at 200 kV.

The monochromatic angle-dispersive powder XRD measure-ments were performed at the 16BM-D beamline of the HighPressure Collaborative Access Team’s facility, at the AdvancedPhoton Source of Argonne National Laboratory. The X-raybeam wavelength was λ = 0.4246 Å. The XRD patterns werecollected with a MAR 345 CCD detector. The intensity versus2θ patterns were obtained using the FIT2D software.20

Refinements of the measured XRD patterns were performedusing the GSAS+EXPGUI software packages.21,22

The Fe−K-edge XAFS measurements were conducted at theBESSY-II storage ring of the Helmholtz Zentrum Berlin. Thespectra were recorded in the KMC-II beamline that is equippedwith a double SiGe (111) graded-crystal monochromator, inthe transmission mode. Fe3O4, FePO4, and FeS compoundswere used for reference purposes. The EXAFS spectra weresubjected to background subtraction and transformation fromthe energy to the k-space. The resulting χ(k) spectra were fittedusing the FEFFIT program.23 The photoelectron scatteringpaths used for the fitting, were constructed with the FEFFcode24 using the magnetite structure with unit cell parameter a= 8.36 Å.The collective magnetic behavior of the iron oxide

nanoparticles was recorded by room temperature hysteresisloops with an Oxford 1.2 H/CF/HT at maximum applied fieldsof 1 T. From each powder sample, an aqueous dispersion (of 2mg Fe/mL) was prepared by the dissolution of nanoparticlesinto distilled water and sonication for 10 min. Thesedispersions were evaluated for their heating efficiency underan AC magnetic field (15, 20, 25 kA/m and 765 kHz).Measurements were performed using a 4.5 kW commercialinductive heater (Ultrahigh Frequency Induction HeatingMachine SPG-10 of Shuangping Corporation). The exper-imental configuration included a glass vial, containing 1 mL ofthe sample, adapted in an insulating holder placed in the centerof water-cooled induction coil. The temperature rise wasrecorded by an OpSens PicoM optic fiber thermometer. Apartfrom the precautions taken regarding insulation and accuracy ofthe temperature measuring point, the estimation of the specificloss power (SLP) value involved a number of calculationsrequired to avoid overestimation errors introduced by the heattransfer from the sample to the environment or from the coilsurface to the sample, as previously discussed.25,26 Thus, byfollowing the modified law of cooling, we are able to quantifymore accurately the heating efficiency, i.e., calculate SLP values.

3. RESULTS AND DISCUSSION

3.1. Morphology and Structure. In Figure 1, wesummarize the TEM results of the various iron oxidenanoparticle batches. Overall, the choice of surfactant doesnot appear to affect the structure and morphology of theobtained MNPs. The shape of the obtained iron oxidenanoparticles is polyhedral in all batches. Figure 1a−e clearlydisplays the tendency of individual nanoparticles to formaggregates in all batches due to hydrophobic interaction, theinherent magnetism of MNPs,12 and van der Waals forces inorder to reduce the surface energy. The SAED pattern revealsthe highly crystalline nature of the iron oxide nanoparticles(shown as inset in Figure 1a). Analysis of the SAED ringsshows that they correspond to the Bragg reflections of the {2 20}, {3 1 1}, {4 0 0}, {5 1 1}, and {4 4 0} crystal planes of eitherFe3O4 or γ-Fe2O3. Furthermore, the single-crystalline nature ofMNPs was gained through the detailed analysis of the

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respective HRTEM images and the corresponding fast Fouriertransforms (Figure 1b−e).We have also estimated the average particle size for each iron

oxide nanoparticle batch (Figure 1f). As it can be seen, theaverage particle size is smaller for the batch prepared withoutany surfactant, whereas the S.C. and PVP-based MNPs exhibit aslightly larger (but almost the same) particle size distribution.Finally, the CTAB-based batch displays the highest averageparticle size distribution values among the iron oxide samples.Hence, it appears that the choice of surfactant influences theiron oxide nanoparticle size distribution, i.e., the nanoparticleaggregation.More detailed structural information on the as-synthesized

iron oxide nanoparticles was obtained from synchrotron-basedXRD measurements. Figure 2 displays the refined XRDpatterns obtained for the differently synthesized batches. In

all cases, the main phase in the XRD spectra is indexed to thecubic Fe3O4 magnetite structure. In addition, small traces of theFeCl3 and FeSO4 reactants are present in all batches asimpurities (Figure 2); the concentration of these foreignphases, however, lies below ∼5% compared to the main phase,as estimated from their relative Bragg peak intensities.In Table 1 we present the main crystallographic parameters

as obtained from the full Rietveld refinements of the XRDpatterns (Figure 2). The different synthesis procedures yieldsimilar results in terms of lattice parameters for the Fe3O4nanoparticles; the lattice parameter values lie in-between thosereported for bulk Fe3O4

27 and γ-Fe2O3,28 with the CTAB-based

batch exhibiting the smallest unit cell constant (Table 1). Inaddition, we have estimated the average crystallite size <d> forall MNP batches by employing Scherrer’s formula (Table 1).The largest crystallite size is obtained when using the S.C.surfactant, whereas the smallest crystallites are produced in thecase of PVP. The average crystallite sizes estimated from theXRD patterns exhibit lower values than the average particlesizes estimated from TEM, whereas they do not follow thesame trend (Figure 1f). Even though the lower crystallite sizevalues compared to the particle size may be attributed to theaggregation of the iron oxide nanoparticles (Figure 1), thecrystallite sizes appear to depend on the choice of surfactant.Finally, we could not observe any clear correlation between

the average crystallite sizes and the respective interatomicparameters, in agreement with Menard et al.29 We should note,however, the presence of Fe vacancies for the CTAB-based andthe S.C.-based iron oxide nanoparticle batches (Table 1). TheseFe vacancies in the magnetite structure imply the oxidation ofthe respective nanoparticle batches, i.e., the transformation ofFe3O4 toward its oxidized analog γ-Fe2O3. Hence, the choice of

Figure 1. (a) Representative TEM image of the iron oxidenanoparticles revealing that only a few surfactant effects on themorphology can be observed. As inset the SAED pattern of the ironoxide nanoparticles. The d-spacing of the SAED rings corresponds to,from bottom to top, {2 2 0}, {3 1 1}, {4 0 0}, {5 1 1}, and {4 4 0}crystal planes of either magnetite or maghemite. High-resolution TEMimages of the MNPs (b) in aqueous solution along a [111] zone axis,(c) in the presence of CTAB as surfactant along a [110] zone axis, (d)in the presence of PVP as surfactant along a [110] zone axis, (e) in thepresence of S.C. as surfactant along a [110] zone axis. Thecorresponding fast Fourier transforms are shown as insets. The scalebar in panel a is 10 nm and for panels b−e is 5 nm. (f) Sizedistribution of all the studied samples.

Figure 2. Refined XRD patterns for the different batches of iron oxidenanoparticles prepared with (top to bottom): an aqueous solutionwithout surfactant, CTAB surfactant, PVP surfactant, and S.C.surfactant. The difference spectra between the measured (opencircles) and the calculated (red lines) XRD patterns are also displayed(black lines). The asterisks and arrows mark the FeCl3 and FeSO4Bragg peaks, respectively.



surfactant seems also to regulate the defects within the crystalstructure.3.2. XAFS Measurements. In order to get a more accurate

microstructural picture, we have additionally performed EXAFSinvestigations on the different iron oxide nanoparticle batches.The normalized to the edge jump Fe−K-edge XANES spectraof the MNPs are shown in Figure 3a. The spectra of thereference compounds Fe3

II,IIIO4, FeIIS, and FeIIIPO4 are also

depicted. Apart from a small blue shift, the spectra of the ironoxide MNPs exhibit strong similarities with the spectrum ofmagnetite. The characteristic pre-edge peak was fitted usingthree Lorentzian functions as shown in the inset. Theabsorption edge was simulated using a sigmoidal functionwith an amplitude equal to 1. According to the fitting resultslisted in Table 2, the different synthesis routes did not result invariations of the Fe oxidation state. In particular, the Fe valencestate in all MNPs lies between 2.8 and 2.9. These values areslightly higher than that of magnetite (2.67), indicating thepartial oxidation of all iron oxide nanoparticle batches. Theseresults partly contradict the XRD measurements (Table 1),where only the CTAB- and the S.C.-based MNP batches arefound to exhibit Fe vacancies or, equivalently, partial oxidation;this discrepancy can be attributed in part to the differentsensitivity of the employed techniques, since XAFS serves as amore short-range and element-specific local probe, whereasXRD detects the average long-range structure of the materialunder study. On the other hand, the pre-edge peak character-istics do not exhibit strong variations, with their values beingcomparable to the corresponding values in magnetite (Table 2).This affinity of the pre-edge peak characteristics indicates thatthe MNPs adopt the spinel structure, consistent with both XRDand TEM studies.The Fe−K-edge EXAFS spectra are shown in Figure 4. In the

magnetite structure, Fe occupies tetrahedral and octahedralsites with a proportion of 1/3 and 2/3, respectively. Bothcontributions were taken into account using the parameter x asthe fraction of Fe atoms that occupy octahedral sites, whereasthe remaining (1−x) occupies tetrahedral sites. The fitting ofthe spectra in the k- and R-space is shown in Figure 4 (upperand lower panel, respectively). The fitting results are listed inTable 3.

Overall, the obtained results indicate that the local bondingenvironment around Fe is similar in all MNPs irrespective ofthe type of surfactant that was used, whereas all iron oxidenanoparticle batches adopt the spinel structure. On the otherhand, the fraction of Fe atoms that occupy octahedral sites isfound slightly higher within the MNPs compared to magnetite;this deviation, however, lies within the error of the performed

Table 1. Structural Parameters for the Various Batches of Fe3O4 Nanoparticlesa

structural parameters Fe3O4 nanoparticle batch

SG Fd3m no surf. CTAB PVP S.C. Fe3O4 bulk γ-Fe2O3 bulk

a (Å) 8.3698(1) 8.3552(1) 8.3663(1) 8.3677(1) 8.392 8.331V (Å3) 586.3 583.3 585.6 585.9 591.1 578.2<d> (nm) 7.3(1) 6.8(3) 6.5(1) 7.6(1)Fetet occ. 0.996(4) 0.917(3) 1.032(3) 1.006(4) 1 1Fetet Uiso (Å

2) 0.0031(3) 0.0039(3) 0.0046(2) 0.0043(4)Feoct occ. 1.021(4) 0.932(3) 1.032(3) 0.95(4) 1 0.833Feoct Uiso (Å

2) 0.0031(3) 0.0039(3) 0.0046(2) 0.0043(4)O-u position 0.2602(2) 0.2606(3) 0.2539(2) 0.2543(2) 0.255 0.2512O occ 1 1 1 1 1 1O Uiso (Å

2) 0.0068(6) 0.0079(5) 0.0099(7) 0.0085(6)(Fe−O)tet × 4 1.963(3) 1.962(4) 1.868(3) 1.874(3) 1.890 1.821(Fe−O)oct × 6 2.011(2) 2.004(3) 2.059(2) 2.057(2) 2.057 2.073wRp (%) 5.9 5.12 4.9 4.78χ2 0.374 0.448 0.309 0.33

aWhere occ = occupancy and Uiso is the isotropic atomic displacement parameter [the Debye−Waller factor is represented as exp(−8π2U sin2 θ/λ2)]. The atomic positions are Fetet: 8a (1/8, 1/8, 1/8), Feoct: 16d (0.5, 0.5, 0.5), and O: 32e (u, u, u).

Figure 3. (a) Fe−K-edge XANES spectra of the MNPs synthesizedusing different types of surfactants (CTAB, S.C., no surfactant, PVP).The spectra of reference Fe3O4 (magnetite), FeIIIPO4, and FeIIScompounds are also included. The inset shows representative fitting ofthe pre-edge peak using three Lorentzian components (L1:7113.3 ±0.1 eV, L2:7114.6 ± 0.1 eV, L3:7116.7 ± 0.2 eV). (b) Determinationof the Fe oxidation state in the MNPs using a linear interpolation ofthe position of the absorption edge of the FeS, Fe3O4, and FePO4compounds.



fitting (Table 3). Finally, the FeOh-O distance in the firstnearest neighboring shell of all MNPs is found slightly smallercompared to the corresponding value in magnetite; suchvariation can be attributed to the partial oxidation of Fe in theMNPs.30

3.3. Magnetic Features. The magnetization versusmagnetic field plots (M−H hysteresis loop) at room temper-ature for all the magnetic nanoparticles is shown in Figure 5.The magnetic characterization reveals the standard ferrimag-netic character exhibited by the spinel iron oxide samples. Themagnetic properties for all the iron oxide nanoparticles arepresented in Table 4. The saturation magnetization MS valuesfor all the prepared samples are suppressed compared to that of“bulk” magnetite (90 A m2/kg),33 which may be attributed to(a) the decrease of particle size: smaller particles yield mildermagnetic features, while below a certain diameter particlesundergo a magnetic transformation from a ferrimagnetic to asuperparamagnetic collective behavior. If the majority of theMNPs reside within the superparamagnetic regime, MNPs

eventually exhibit a smaller saturation magnetization comparedto bulk values since a small fraction of particles only contributesto the overall behavior. (b) The relatively large particle sizedistributions originating from the coprecipitation synthesisroute: since the blocking temperature depends on particle size,a wide size distribution will result in a wide range of blockingtemperatures and, hence, nonoptimum magnetic behavior dueto polydispersity issues.1,13,34

The improved crystallinity of the nanoparticles, as deducedfrom the TEM and XRD measurements, facilitates to maintainthe saturation magnetization at relatively high values. The MSvalues reported in Table 4 for all the synthesized MNPs arevery close to iron oxide samples of similar sizes.35 In addition,the saturation magnetization of the iron oxide prepared in thepresence of the surfactant CTAB is lower than that of the otherthree samples. This behavior can be ascribed to the presence ofprominent Fe vacancies in the CTAB-based batch as discussedin previous section (Table 1).36 Nevertheless, even smaller MSvalues (7−22 Am2/kg) are reported as being exploitable forbioapplications.37

Superparamagnetism is an essential feature of the magneticnanoparticles, since after the removal of the external magneticfield, the magnetization disappears and, hence, the agglomer-ation and the possible embolization of the capillary vessels canbe avoided.38,39 From Table 4 we see that the coercivity Hcexhibits a small value at room temperature, indicating anegligible (almost zero) ferrimagnetic character of the systemsunder study, which is a characteristic attribute for super-paramagnetic materials.38 Furthermore, the remanent magnet-ization (Mr) is also close to zero for all samples. Thesemagnetic features show that the measured MNPs can be easilymanipulated under an external magnetic field, but they will notpreserve any residual magnetism upon the removal of theexternal field.

3.4. Hyperthermia. When magnetic nanoparticles areexposed in an alternating magnetic field, there are differentmechanisms that produce heat at the surrounding regions. Inthe case of superparamagnetic nanoparticles, the effect isattributed to Neel and/or Brown relaxation mechanisms while,the heat dissipation in the ferro(i)magnetic regime is mainlyattributed to hysteresis losses.40

The SLP, defined as the energy conversion rate (W/g), is agauge of the heating conversion efficiency and needs to bemaximized. Since SLP strongly depends on the particle (size,composition, and magnetic profile) and field (intensity andfrequency) parameters, the various approaches for enhancingSLP results in lower dosage level of nanoparticles and milderfield conditions. The SLP values are proportional to thesaturation magnetization MS of nanoparticles and show amaximum point for a certain particle size and magneticanisotropy constant, whereas they are inversely proportional tothe size distribution of the nanoparticles.41,42

The hyperthermia response of the four samples iscomparatively illustrated in Figure 6. In all cases, the solutionconcentration and field frequency were kept constant at 2 mg/mL and 765 kHz respectively, while the magnitude of magneticfield was varying. It should be mentioned here that despite theuse of a relatively high frequency (765 kHz), which leads inturn in a H·f product at least 1 order of magnitude above theestimated threshold for major discomfort (∼5 × 108 A m−1

s−1), analogous protocols are currently examined (also in vitro)as alternatives to overcome the usual constraints of limitedheating efficacy.43

Table 2. Fitting Results of the Pre-Edge Peak of the XANESSpectraa

area (arb units)

sample L1 L2 L3edge position

(eV)oxidationstate

Fe3O4 0.27 0.09 0.00 7121.6(2) 2.67(3)no surfactant 0.22 0.16 0.10 7122.7(2) 2.80(3)CTAB 0.25 0.16 0.10 7123.1(2) 2.86(3)S.C. 0.25 0.14 0.10 7123.0(2) 2.84(3)PVP 0.19 0.14 0.08 7122.9(2) 2.84(3)aNote: L1, L2, and L3 are the three Lorentzian functions with energypositions 7113.3 ± 0.1, 7114.6 ± 0.1, and 7116.7 ± 0.2 eV,respectively, that were used to fit the pre-edge peak.

Figure 4. χ(k) (top) and Fourier Transform of the k3χ(k) (bottom)EXAFS spectra of the MNPs synthesized using different types ofsurfactants. The experimental and fitting curves are shown in thin andthick solid lines, respectively.



Figure 6a displays the temperature variation for threedifferent magnetic field magnitudes (15, 20, 25 kA/m) forthe four samples, the first indication of heating response.expected, the strength of heating effect is proportional to themagnitude of the field, showing the magnetic origin of thisbehavior. It can also be seen that the choice of surfactantstrongly affects the collective heating response (Figure 6a), andthat the effect may be further optimized upon the propersurfactant choice. As discussed in the previous section, theCTAB-based batch yields milder magnetic features (Figure 5and Table 4), which are exhibited directly in hyperthermiameasurements, since it is widely accepted that the higher themagnetization (along with coercivity, remanence, and magneticanisotropy), the higher the AC heating response.44 It seemsthat the more prominent oxidation of the CTAB-based MNPssuppresses both the collective magnetic response, as well as theAC heating effect of this batch compared to the other MNPs.On the other hand, the batch synthesized without anysurfactant maintains a relatively high saturation magnetizationand reduces remanence and coercivity compared to the othertwo surfactant-covered samples (S.C., PVP), indicating thebeneficial role of better crystallinity, size dispersion, andhomogeneity in collective magnetic and AC heating response.On the contrary, the implementation of S.C. and PVP assurfactants leads to a much higher heating response. The latteris also depicted in Figure 6b, where the quantifiable measure ofheating response, i.e., the SLP index against field magnitude isplotted for all samples. It seems that both S.C. and PVPsurfactants manage to maintain colloidal and structural stability,as well as size homogeneity, though not significantlyattenuating the collective magnetic features. The SLP values

Table 3. Fitting Results of the EXAFS Analysisa

model sample

Fe3O4c γ-Fe2O3

d Fe3O4 CTAB S.C. no surf. PVP

shell x = 0.67b 0.76 ± 0.19 0.74 ± 0.13 0.77 ± 0.08 0.74 ± 0.09

FeOh-O N1 4 3.4 4.0b 4.5 4.4 4.6 4.5N = 6x R1 ± 0.01 2.05 2.08 2.02 1.96 1.97 1.97 1.97

σ12 ± 15% 0.0117 0.0089 0.0079 0.0076 0.0073

FeTd-O N2 1.33 1.7 1.33b 1.0 1.0 1.0 1.0N = 4(1−x) R2 ± 0.01 1.89 1.80 1.88 1.88 1.88 1.88 1.88

σ22 ± 15% 0.0123 0.0093 0.0083 0.0080 0.0077

FeOh-FeOh N3 (Fe) 4 2.6 4.0b 4.5 4.4 4.6 4.5N = 6x R3 ± 0.02 2.97 2.94 2.98 3.01 3.00 3.00 3.00

σ32 ± 25% 0.0103 0.0126 0.0100 0.0098 0.0099

FeOh-FeTd FeTd- FeOh N4 (Fe) 8 6.9 8.0b 7.4 7.5 7.4 7.5N = 6x + 12(1−x) R4 ± 0.02 3.48 3.45 3.49 3.47 3.47 3.48 3.48

σ42 ± 25% 0.0088 0.0131 0.0101 0.0099 0.0101

FeOh,Td-O N5 (O) 4 5.1 8.0b 7.4 7.5 7.4 7.5N = 6x + 12(1−x) 4 3.4

R5 ± 0.05 3.49 3.45 3.58 3.64 3.54 3.58 3.573.66 3.60

σ52 ± 40% 0.0280 0.0333 0.0294 0.0294 0.0296

FeTd-FeTd N6 (Fe) 1.33 1.7 1.33b 1.0 1.0 0.9 1.0N = 4x R6 ± 0.05 3.63 3.60 3.64 3.62 3.62 3.62 3.62

σ62 ± 40% 0.0271 0.0322 0.0288 0.0287 0.0289

aNote: N is the coordination number, x is the fraction of Fe atoms that occupy octahedral sites, R the nearest neighbor distance in Å, and σ2 is theDebye−Waller factor in Å2. The energy origin (3.8 ± 0.3 eV) and the amplitude reduction factor (0.78 ± 0.03) were commonly iterated for all thesamples. The reported errors correspond to the fitting uncertainties. The first column indicates the type of the nearest neighbors and the octahedral(Oh) or tetrahedral (Td) site occupied by the absorbing atom. bNon-iterated values. cRef 31; space group: Fd3m; a = 8.3922 Å; atom positions: FeTd(0.125, 0.125, 0.125), FeOh (0.5, 0.5, 0.5), O (0.255, 0.255, 0.255). dRef 32; space group: P4132; a = 8.33 Å; atom positions: FeTd (0.5, 0.5, 0.5), FeOh(0.875, 0.875, 0.875), FeOh (0.125, 0.875, 0.125), O (0.125, 0.125, 0.625), O (0.625, 0.625, 0.625).

Figure 5. Magnetic hysteresis loops for the four as-synthesized ironoxide nanoparticles recorded at room temperature and maximum fieldof 1 T. Details of the magnetization curves of the four as-synthesizediron oxide nanoparticles for field values in the range −0.25−0.25 T areshown in the inset.

Table 4. Magnetic Properties of the Iron OxideNanoparticlesa

MS (Am2/kg) Mr (Am

2/kg) Hc (T)

no surfactant 47.5 1.5 0.005Fe3O4 surfactant CTAB 29.8 0.7 0.009Fe3O4 surfactant S.C. 46.3 5.6 0.014Fe3O4 surfactant PVP 50 4.2 0.010

aMr is defined as the magnetization at H = 0, Hc defined as the fieldmagnitude necessary to obtain M = 0.



attained for these samples ( ≥200 W/g at 25 KA/m) renderthem as suitable hyperthermia agents.45 Further optimization ofmagnetostructural features via synthetic optimization isexpected to establish stronger ferrimagnetic behavior andenhance subsequently the heating response.

4. CONCLUSIONSIn summary, magnetic iron oxide nanoparticles have beensynthesized through the widely used coprecipitation methodwith (and without) the use of three common surfactants,namely, CTAB, S.C., and PVP. All of the obtained MNPbatches have been characterized in detail with a multi-experimental approach, namely, with TEM, synchrotron-basedXRD and XAFS, as well as with magnetic measurements.The TEM measurements on the various iron oxide

nanoparticle batches have not revealed any surfactant effectson the morphological properties of the MNPs. On the otherhand, the estimated average particle and crystallite sizedistribution appears to depend on the choice of surfactant. Inaddition, the presence of defects within the spinel structure, i.e.,oxidation of the MNPs seems to be also influenced by thechoice of surfactant. These structural deviations among thevarious iron oxide nanoparticle batches affect directly themagnetic properties of the MNPs.In particular, the CTAB-based batch yields the milder

magnetic features compared to the rest of the samples due to itsmore prominent oxidation. Nevertheless, the remanent magnet-ization and coercivity are found to attenuate at roomtemperature due to finite-size effects for all iron oxide batches,indicating a superparamagnetic nature of the nanoparticles, aprerequisite in most biomedical applications. Furthermore, it isfound that the iron oxide nanoparticles synthesized with the useof PVP and S.C. as surfactants exhibit a higher heat capacityunder an alternating magnetic field compared to the other ones.Thus, by proper choice of the surfactant, the nanoparticlesmaintain collective magnetic features along with an enhancedAC magnetic heating response, making them good candidatesfor hyperthermia modalities.Finally, we should point out that a direct comparison

between the three surfactants employed in this work is notpossible due to their significant physicochemical differences.Nevertheless, it has been shown that the distinctive features ofeach surfactant (e.g., polar headgroup size and charge,hydrophobic chain length) may strongly influence themorphological (e.g., the nanoparticle aggregation), structural

(stoichiometry), and magnetic properties of the producedMNPs.36 These results can serve as a first step toward theunderstanding of the correlation between the choice ofsurfactant and its effect on the magnetostructural propertiesof iron oxide nanoparticles synthesized by the coprecipitationmethod, and further enhance their application in magneticparticle hyperthermia.

■ AUTHOR INFORMATION

Corresponding Author*Tel.:+32 3 265 35 29; fax: +32 3 265 33 18; e-mail: [email protected].

NotesThe authors declare no competing financial interest.

■ ACKNOWLEDGMENTS

G.V.T. and M.F. acknowledge funding from the EuropeanResearch Council under the seventh Framework Program(FP7), ERC Grant No. 246791 − COUNTATOMS. This workis also performed within the framework of the IAP-PAI. TheEXAFS characterization was financially supported from theEuropean Community’s 7th Framework Program (FP7/2007-2013) under Grant Agreement No. 226716. Part of this workwas performed at HPCAT (Sector 16), Advanced PhotonSource (APS), Argonne National Laboratory (ANL). HPCAToperations are supported by DOE-NNSA under Award No.DE-NA0001974 and DOE-BES under Award No. DE-FG02-99ER45775, with partial instrumentation funding by NSF. APSis supported by DOE-BES, under Contract No. DE-AC02-06CH11357. We would like to thank Dr. D. Popov and Mr. T.Lochbiler for their assistance with the XRD measurements.

■ REFERENCES(1) Wu, W.; He, Q.; Jiang, C. Magnetic Iron Oxide Nanoparticles:Synthesis and Surface Functionalization Strategies. Nanoscale Res. Lett.2008, 3, 397−415.(2) Li, D.; Teoh, W. Y.; Selomulya, C.; Woodward, R. C.; Munroe,P.; Amal, R. Insight into Microstructural and Magnetic Properties ofFlame-Made Γ-Fe2O3 Nanoparticles. J. Mater. Chem. 2007, 17, 4876−4884.(3) Veiseh, O.; Gunn, J. W.; Zhang, M. Design and Fabrication ofMagnetic Nanoparticles for Targeted Drug Delivery and Imaging. Adv.Drug Delivery Rev. 2010, 62, 284−304.

Figure 6. (a) Temperature rise and (b) the corresponding SLP values for samples under study.



mailto:[email protected]

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(4) Salas, G.; Veintemillas-Verdaguer, S.; Morales, M. D. P.Relationship between Physico-Chemical Properties of Magnetic Fluidsand Their Heating Capacity. Int. J. Hyperthermia 2013, 29, 768−776.(5) Filippousi, M.; Papadimitriou, S. A.; Bikiaris, D. N.; Pavlidou, E.;Angelakeris, M.; Zamboulis, D.; Tian, H.; Van Tendeloo, G. NovelCore−shell Magnetic Nanoparticles for Taxol Encapsulation inBiodegradable and Biocompatible Block Copolymers: Preparation,Characterization and Release Properties. Int. J. Pharm. 2013, 448,221−230.(6) Filippousi, M.; Altantzis, T.; Stefanou, G.; Betsiou, M.; Bikiaris,D. N.; Angelakeris, M.; Pavlidou, E.; Zamboulis, D.; Van Tendeloo, G.Polyhedral Iron Oxide Core-Shell Nanoparticles in a BiodegradablePolymeric Matrix: Preparation, Characterization and Application inMagnetic Particle Hyperthermia and Drug Delivery. RSC Adv. 2013, 3,24367−24377.(7) Pankhurst, Q. A.; Connolly, J.; Jones, S. K.; Dobson, J.Applications of Magnetic Nanoparticles in Biomedicine. J. Phys. DApp Phys. 2003, 36, R167−R181.(8) Nguyen, X. P.; Tran, D. L.; Ha, P. T.; Pham, H. N.; Mai, T. T.;Pham, H. L.; Le, V. H.; Do, H. M.; Hoa Phan, T. B.; Giang Pham, T.H.; et al. Iron Oxide-Based Conjugates for Cancer Theragnostics. Adv.Nat. Sci. Nanosci. Nanotechnol. 2012, 3, 033001.(9) Shubayev, V. I.; Pisanic, T. R.; Jin, S. Magnetic Nanoparticles forTheragnostics. Adv. Drug Delivery Rev. 2009, 61, 467−477.(10) Ling, D.; Hyeon, T. Chemical Design of Biocompatible IronOxide Nanoparticles for Medical Applications. Small 2013, 9, 1450−1466.(11) Marciello, M.; Connord, V.; Veintemillas-Verdaguer, S.; Verges,M. A.; Carrey, J.; Respaud, M.; Serna, C. J.; Morales, M. P. Large ScaleProduction of Biocompatible Magnetite Nanocrystals with HighSaturation Magnetization Values through Green Aqueous Synthesis.J. Mater. Chem. B 2013, 1, 5995−6004.(12) Wan, J.; Tang, G.; Qian, Y. Room Temperature Synthesis ofSingle-Crystal Fe3O4 Nanoparticles with Superparamagnetic Property.Appl. Phys. A: Mater. Sci. Process. 2007, 86, 261−264.(13) Lu, A.-H.; Salabas, E. L.; Schuth, F. Magnetic Nanoparticles:Synthesis, Protection, Functionalization, and Application. Angew.Chem. 2007, 46, 1222−1244.(14) Santos, L.; Rodrigues, D.; Lira, M.; Oliveira, R.; Real Oliveira,M. E. C. D.; Vilar, E. Y.-P.; Azeredo, J. The Effect of Octylglucosideand Sodium Cholate in Staphylococcus Epidermidis and PseudomonasAeruginosa Adhesion to Soft Contact Lenses. Optom. Vis. Sci. 2007,84, 429−434.(15) Arsalani, N.; Fattahi, H.; Nazarpoor, M. Synthesis andCharacterization of PVP-Functionalized Superparamagnetic Fe3O4

Nanoparticles as an MRI Contrast Agent. eXPRESS Polym. Lett.2010, 4, 329−338.(16) Zhang, Y.; Xu, D.; Li, W.; Yu, J.; Chen, Y. Effect of Size, Shape,and Surface Modification on Cytotoxicity of Gold Nanoparticles toHuman HEp-2 and Canine MDCK Cells. J. Nanomater. 2012, 2012,1−7.(17) Qiu, Y.; Liu, Y.; Wang, L.; Xu, L.; Bai, R.; Ji, Y.; Wu, X.; Zhao,Y.; Li, Y.; Chen, C. Surface Chemistry and Aspect Ratio MediatedCellular Uptake of Au Nanorods. Biomaterials 2010, 31, 7606−7619.(18) Murphy, C. J.; Gole, A. M.; Stone, J. W.; Sisco, P. N.; Alkilany,A. M.; Goldsmith, E. C.; Baxter, S. C. Gold Nanoparticles in Biology:Beyond Toxicity to Cellular Imaging. Acc. Chem. Res. 2008, 41, 1721−1730.(19) Gong, T.; Goh, D.; Olivo, M.; Yong, K.-T. In Vitro Toxicity andBioimaging Studies of Gold Nanorods Formulations Coated withBiofunctional Thiol-PEG Molecules and Pluronic Block Copolymers.Beilstein J. Nanotechnol. 2014, 5, 546−553.(20) Hammersley, A. P.; Svensson, S. O.; Hanfland, M.; Fitch, A. N.;Hausermann, D. Two-Dimensional Detector Software: From RealDetector to Idealised Image or Two-Theta Scan. High Press. Res. 1996,14, 235−248.(21) Larson, A. C.; Von Dreele, R. B. General Structure AnalysisSystem (GSAS). Los Alamos Natl. Lab. Rep. LAUR 2004, 748, 86−748.

(22) Toby, B. H. EXPGUI, a Graphical User Interface for GSAS. J.Appl. Crystallogr. 2001, 34, 210−213.(23) Newville, M.; Ravel, B.; Haskel, D.; Rehr, J. J.; Stern, E. A.;Yacoby, Y. Analysis of Multiple-Scattering XAFS Data UsingTheoretical Standards. Phys. B 1995, 208&209, 154−156.(24) Ankudinov, A. L.; Ravel, B.; Rehr, J. J.; Conradson, S. D. Real-Space Multiple-Scattering Calculation and Interpretation of X-Ray-Absorption near-Edge Structure. Phys. Rev. B 1998, 58, 7565−7576.(25) Chalkidou, A.; Simeonidis, K.; Angelakeris, M.; Samaras, T.;Martinez-Boubeta, C.; Balcells, L.; Papazisis, K.; Dendrinou-Samara,C.; Kalogirou, O. In Vitro Application of Fe/MgO Nanoparticles asMagnetically Mediated Hyperthermia Agents for Cancer Treatment. J.Magn. Magn. Mater. 2011, 323, 775−780.(26) 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.(27) Fleet, M. E. The Structure of Magnetite: Symmetry of CubicSpinels. J. Solid State Chem. 1986, 62, 75−82.(28) Yusuf, S. M.; De Teresa, J. M.; Mukadam, M. D.; Kohlbrecher,J.; Ibarra, M. R.; Arbiol, J.; Sharma, P.; Kulshreshtha, S. K.Experimental Study of the Structural and Magnetic Properties of γ-Fe2O3 Nanoparticles. Phys. Rev. B 2006, 74, 224428−11.(29) Menard, M. C.; Marschilok, A. C.; Takeuchi, K. J.; Takeuchi, E.S. Variation in the Iron Oxidation States of Magnetite Nanocrystals asa Function of Crystallite Size: The Impact on ElectrochemicalCapacity. Electrochim. Acta 2013, 94, 320−326.(30) Kanowitz, S. M.; Palenik, G. J. Bond Valence Sums inCoordination Chemistry Using Oxidation-State-Independent R 0Values. A Simple Method for Calculating the Oxidation State ofIron in Fe-O. Inorg. Chem. 1998, 37, 2086−2088.(31) Okudera, H.; Kihara, K.; Matsumoto, T. TemperatureDependence of Structure Parameters in Natural Magnetite: SingleCrystal X-Ray Studies from 126 to 773 K. Acta Crystallogr. 1996, 52,450−457.(32) Pecharroman, C.; Gonzalez-Carreno, T.; Iglesias, J. E. TheInfrared Dielectric Properties of Maghemite, γ-Fe2O3, fromReflectance Measurement on Pressed Powders. Phys. Chem. Miner.1995, 22, 21−29.(33) Gupta, A. K.; Gupta, M. Synthesis and Surface Engineering ofIron Oxide Nanoparticles for Biomedical Applications. Biomaterials2005, 26, 3995−4021.(34) 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, 054430−054439.(35) Simeonidis, K.; Mourdikoudis, S.; Tsiaoussis, I.; Angelakeris, M.;Dendrinou-Samara, C.; Kalogirou, O. Structural and MagneticFeatures of Heterogeneously Nucleated Fe-Oxide Nanoparticles. J.Magn. Magn. Mater. 2008, 320, 1631−1638.(36) Lu, T.; Wang, J.; Yin, J.; Wang, A.; Wang, X.; Zhang, T.Surfactant Effects on the Microstructures of Fe3O4 NanoparticlesSynthesized by Microemulsion Method. Colloids Surf., A 2013, 436,675−683.(37) Xu, C.; Xu, K.; Gu, H.; Zhong, X.; Guo, Z.; Zheng, R.; Zhang,X.; Xu, B. Nitrilotriacetic Acid-Modified Magnetic Nanoparticles as aGeneral Agent to Bind Histidine-Tagged Proteins. J. Am. Chem. Soc.2004, 126, 3392−3393.(38) Zhou, Z. H.; Wang, J.; Liu, X.; Chan, H. S. O. Synthesis ofFe3O4 Nanoparticles from Emulsions. J. Mater. Chem. 2001, 11, 1704−1709.(39) Laurent, S.; Mahmoudi, M. Superparamagnetic Iron OxideNanoparticles: Promises for Diagnosis and Treatment of Cancer. Int. J.Mol. Epidemiol. Genet. 2011, 2, 367−390.(40) 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 by



Tuning Dipole-Dipole Interactions. Adv. Funct. Mater. 2012, 22,3737−3744.(41) Hergt, R.; Dutz, S.; Zeisberger, M. Validity Limits of the NeelRelaxation Model of Magnetic Nanoparticles for Hyperthermia.Nanotechnology 2010, 21, 015706.(42) Vallejo-Fernandez, G.; Whear, O.; Roca, a G.; Hussain, S.;Timmis, J.; Patel, V.; O’Grady, K. Mechanisms of Hyperthermia inMagnetic Nanoparticles. J. Phys. D Appl. Phys. 2013, 46, 312001.(43) Kozissnik, B.; Bohorquez, A. C.; Dobson, J.; Rinaldi, C.Magnetic Fluid Hyperthermia: Advances, Challenges, and Oppor-tunity. Int. J. Hyperthermia 2013, 29, 706−714.(44) Bakoglidis, K. D.; Simeonidis, K.; Sakellari, D.; Stefanou, G.;Angelakeris, M. Size-Dependent Mechanisms in AC MagneticHyperthermia Response of Iron-Oxide Nanoparticles. IEEE Trans.Magn. 2012, 48, 1320−1323.(45) 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.



surfactant effects on the structural and magnetic properties of iron oxide nanoparticles

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