Journal of the Korean Physical Society, Vol. 68, No. 4, February 2016, pp. 587∼592

Control of the Saturation Temperature in Magnetic Heating by UsingPolyethylene-glycol-coated Rod-shaped Nickel-ferrite (NiFe2O4) Nanoparticles

Yousaf Iqbal, Hongsub Bae and Ilsu Rhee∗

Department of Physics, Kyungpook National University, Daegu 41566, Korea

Sungwook Hong

Division of Science Education, Daegu University, Gyeongsan 38453, Korea

(Received 20 November 2015)

Polyethylene-glycol (PEG)-coated nickel-ferrite nanoparticles were prepared for magnetic hyper-thermia applications by using the co-precipitation method. The PEG coating occurred during thesynthesis of the nanoparticles. The coated nanoparticles were rod-shaped with an average lengthof 16 nm and an average diameter of 4.5 nm, as observed using transmission electron microscopy.The PEG coating on the surfaces of the nanoparticles was confirmed from the Fourier-transforminfrared spectra. The nanoparticles exhibited superparamagnetic characteristics with negligible co-ercive force. Further, magnetic heating effects were observed in aqueous solutions of the coatednanoparticles. The saturation temperature could be controlled at 42 ◦C by changing the concen-tration of the nanoparticles in the aqueous solution. Alternately, the saturation temperature couldbe controlled for a given concentration of nanoparticles by changing the intensity of the magneticfield. The Curie temperature of the nanoparticles was estimated to be 495 ◦C. These results forthe PEG-coated nickel-ferrite nanoparticles showed the possibility of utilizing them for controlledmagnetic hyperthermia at 42 ◦C.

PACS numbers: 81.05.Ni, 76.60.Es, 61.46.Df, 87.61.-cKeywords: Nickel-ferrite nanoparticles, Saturation temperature, Polyethylene-glycol coating, Curie temper-atureDOI: 10.3938/jkps.68.587

I. INTRODUCTION

Nanoparticles have attracted great attention, owing totheir characteristic chemical, optical, electrical, mechani-cal, and magnetic properties that are different from thoseof the corresponding bulk systems [1–3]. These peculiarproperties originate from their high reactivity with othermaterials due to their large surface area to volume ratioas well as their quantum size effects. The high reactivityof the nanoparticles is utilized in nanoparticle catalysis,nano drug delivery, and improvement of wear resistance.On the other hand, the peculiar optical and electricalproperties of nanoparticles that have a size smaller thanthe electron’s de Broglie wavelength are different fromthose of bulk systems owing to the quantum size effects.In addition, quantum confinement causes transparencyof titanium-oxide nanoparticles, block of ultraviolet inantimony-tin-oxide nanoparticles, and changes in the flu-orescence with particle size for gold nanoparticles [4–6].

Nanostructures can exist various forms, including li-posomes, polymeric micelles, dendrimers, nanoparticles,

∗E-mail: ilrhee@knu.ac.kr

nanocapsules, and carbon nanotubes [7]. Among thosenanostructures, nanoparticles of various materials andshapes have been investigated from the point of view ofutilizing them in biomedical applications. In particular,magnetic nanoparticles are useful for both the diagnosisand the treatment of diseases owing to their magneticproperties. In addition, magnetic nanoparticles are use-ful as carriers in nano-drug delivery systems owing tothe possibility of tracing the systems with magnetic res-onance imaging (MRI). Various magnetic nanoparticlesare being used as MRI contrast agents. In addition, mag-netic nanoparticles can be utilized for the internal mag-netic hyperthermia treatment of cancer. In the mag-netic hyperthermia treatment procedure, the magneticnanoparticles are used as heat generators under an al-ternating magnetic field, and the difference in the heatresistance between normal and cancer cells is exploitedfor treatment.

Magnetic nanoparticles are toxic; therefore, surfacemodification of the nanoparticles is required in orderto apply them to the human body. Surface modifica-tion is also required for labeling various chemicals suchas drugs and targeting ligands on their surfaces. Vari-

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ous biocompatible materials are used for surface modi-fication, including polyethylene glycol (PEG), chitosan,dextran, carbon, gold, and oleic acid [8–13].

In the current study, rod-shaped nickel-ferritenanoparticles were prepared for magnetic hyperthermiaapplications. The nanoparticles were coated with PEGto achieve biocompatibility. The superparamagneticproperties of these nanoparticles were confirmed by usinga vibrating sample magnetometer (VSM). Aqueous solu-tions containing coated nanoparticles in various concen-trations were prepared for checking the magnetic heat-ing effect. In addition, the dependence of the specificabsorption rate (SAR) on the concentration of nanopar-ticles was observed. The dependence of the intensity ofheating on the nanoparticle concentration was also ex-amined.

II. EXPERIMENTS

Bivalent metals (M2+, where M = Fe, Co, Mn, Ni, etc.)and trivalent Fe3+ ions can be co-precipitated from theiraqueous salt solutions by adding alkaline solutions suchas NH4OH and NaOH to the salt solutions. In this study,we used the co-precipitation method for formulating thenickel-ferrite nanoparticles. The surfaces of the parti-cles were coated during the synthesis of the nanoparti-cles themselves [10, 14]. In brief, 3 mL of an aqueoussolution of 0.3-M NiCl2·4H2O was first mixed with 3 mLof an aqueous solution of 0.6-M FeCl3·6H2O. Followingthis, 6 mL of 2% (w/w) PEG solution was added to thismixture in a 250-mL double-walled beaker. The temper-ature of the water circulating across the double-walledbeaker was maintained at 4 ◦C. Air bubbles were in-troduced into this mixture for 1 h by using a pipette.As the nanoparticles were formed, PEG adhered to theirsurfaces at a pH of around 7. To achieve this pH, we hadadded 1% (v/v) NaOH drop-wise to the metal salt - PEGsolution mixture at a rate of 1 mL/min. For stabilizationof the nanoparticles, the final solution was placed in anultrasonic environment for 10 h, following which the so-lution was filtered using a 100-nm filter. The size of thenanoparticle depends on the ultrasonic treatment timebecause ultrasonic treatment provides energy to dissoci-ate the excess PEG from the coated particles. Powdersamples of the coated nanoparticles were obtained bykeeping the wet particles at 35 ◦C in air for about 12days.

Aqueous solutions of the nickel-ferrite nanoparticleswere prepared for investigating the heating effect of themagnetic nanoparticles under an alternating magneticfield. A powder sample of the PEG-coated nickel-ferritenanoparticles (20 mg) was dispersed in 50 mL of deion-ized water by means of ultrasonication for 20 min. Thedispersion was kept in air for 6 to 10 days, allowingthe uncoated nanoparticles to precipitate to the bottom.The upper solution was then collected carefully by using

a 50-mL syringe. The resultant dispersion was observedto be highly stable for months. This dispersion of nickel-ferrite nanoparticles was very dilute. A concentratedsample was obtained by placing the dilute solution ina vacuum oven at 40 ◦C for about 5 days. The amountsof nickel and iron in the aqueous solution were measuredby using inductively coupled plasma (ICP) spectrome-try. Four additional samples were prepared by dilutingthe concentrated sample to 75%, 50%, 37.5%, and 25%in order to measure the effect of concentration on themagnetic heating effect.

The morphology and the particle size distributionof the nickel-ferrite nanoparticles were analyzed usingtransmission electron microscopy (TEM; H-7600, Hi-tachi Ltd.). The bonding of PEG on the surface of thenanoparticles was confirmed using Fourier transform in-frared spectroscopy (FTIR; Nicolet 380, Thermo Scien-tific USA). The magnetic measurements were carried outusing VSM (MPMS, Quantum Design). The chemicalcomposition and concentration of the coated nanoparti-cles in the aqueous solution were measured using ICPspectrometery (Thermo Jarrell Ash IRISAP). Further,the magnetic heating effects of the nanoparticles dis-persed in water were measured using an induction heat-ing system (Osung High Tech, OSH-120-B). The tem-perature of the solution was measured with a CALEXinfrared thermometer (PyroUSB CF, Calex ElectronicsLimited).

III. RESULTS AND DISCUSSION

Figure 1 shows a TEM image of the coated nickel-ferrite nanoparticles. The PEG-coated nanoparticles arerod-shaped with a uniform size distribution, an averagelength of 16 nm and an average diameter of 4.5 nm. Thesize distributions of one hundred nanoparticles obtainedfrom a TEM image are shown in the histogram in Fig. 1.

Figure 2 shows the hysteresis curve of the PEG-coatednickel-ferrite nanoparticles at room temperature. Fromthe figure in the inset, the zero remanence and coercivityare apparent, indicating that the nanoparticles exhibitsuperparamagnetic properties at room temperature. Thesuperparamagnetic behavior is desirable for biomedi-cal applications because superparamagnetic nanoparti-cles exhibit magnetic behavior only under the influenceof external magnetic fields.

The FTIR spectra of PEG-coated nickel-ferritenanoparticles are shown in Fig. 3. Two absorption bandsat 640 and 470 cm−1 are observed due to the metal-oxygen stretching vibrations at the tetrahedral and oc-tahedral sites, respectively [15]. The absorption band at1,100 cm−1 corresponds to the stretching of the C−O−Cbonding in the −CH2−O−CH2− group of PEG [16,17].On the other hand, the absorption bands at 3,410 and1,630 cm−1 are attributed to the stretching and vibra-

Control of the Saturation Temperature in Magnetic Heating · · · – Yousaf Iqbal et al. -589-

Fig. 1. (Color online) TEM image and size distribution ofthe nanoparticles. The histograms show the length and widthdistributions of one hundred nanoparticles obtained from theTEM image.

Fig. 2. (Color online) Hysteresis curve for a powder sampleof the coated nanoparticles. The figure in the inset indicatesa negligible coercive force.

tion of the O−H bond, respectively. Further, the absorp-tion bands at 2,870, 1,400, 1,250, and 950 cm−1 are dueto symmetric stretching, scissoring (in-plane bending),

Fig. 3. (Color online) FTIR spectra for the coatednanoparticles.

Fig. 4. Schematic of the induction heating system.

twisting stretching, and out-of-plane bending vibrationof the C−H bond, respectively [17]. These results clearlyconfirm the bonding of PEG on the surfaces of the nickel-ferrite nanoparticles.

The amounts of nickel and iron in the concentratedaqueous solution were measured by ICP spectrometryto be 2,452 and 6,273 mg/L, respectively. The atomicratio of iron to nickel is 2.17, which is approximatelyconsistent with the chemical formula of NiFe2O4. As westated previously, four additional samples were preparedby diluting the concentrated sample to 75%, 50%, 37.5%,and 25%. While the nanoparticle concentration in theconcentrated sample was 8.7 mg/mL, the nanoparticleconcentrations in the 75%, 50%, 37.5%, and 25% dilutedsamples were 6.5, 4.3, 3.2, and 2.2 mg/mL, respectively.

A schematic figure of the induction heating systemused for observing the magnetic heating effects is shownin Fig. 4. Aqueous samples of the nanoparticles wereplaced in the RF coil with a resonance frequency of 260kHz. Field strengths of 2.3, 3.9, and 5.5 kA/m were usedto observe the effect of the field strength on the magneticheating effect. An IR thermometer located 10 cm abovethe sample was used to measure the temperature of thesample.

When a magnetic system is subjected to an alternat-ing magnetic field, heat is generated due to certain lossmechanisms, which can be classified as hysteresis andrelaxation loss [18]. The latter can be further dividedinto Neel and Brown losses. Because the superparam-agnetic nanoparticles in our case show no hysteresis, as

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Fig. 5. (Color online) Effect of concentration on magneticheating. The 4.3-mg/mL sample shows a saturation temper-ature of 42 ◦C.

indicated in Fig. 2, we can neglect the hysteresis losses.Ferromagnetic resonance loss can also be ignored in thepresent study because it occurs in the GHz frequencyrange, which is much larger than the 200 − 300 kHz fre-quency range used in this study. Thus, the remainingheating mechanisms for the nanoparticles are Neel andBrown losses. The background heating effects caused bypure water and the sample container were estimated andwere observed to be negligible.

Aqueous samples (1 mL) taken in thermally-insulatedcontainers were placed under an alternating magneticfield. The increase in the temperature as a function of theheating time for five samples with different concentra-tions of nickel-ferrite nanoparticles are shown in Fig. 5.The magnetic field intensity was fixed at 5.5 kA/m witha frequency of 260 kHz. We can see from Fig. 5 that thetemperature of the concentrated sample increases fasterthan that of the diluted samples. This dependence of thetemperature rise on the concentration of nanoparticles isexpected because more heat generators (nanoparticles)are present in the concentrated sample. All the sam-ples are also observed to reach saturation temperaturesafter about 1,000 s. At this time, heat generation is bal-anced by heat loss. The saturation temperatures for the8.7-, 6.5-, 4.3-, 3.2-, and 2.2-mg/mL samples were 48,45, 42, 41, and 39 ◦C, respectively. During the mag-netic hyperthermia treatment, the temperature shouldbe maintained at 42 ◦C for 30 min to kill the malig-nant tissues. At the same time, the temperature shouldalso be kept below 46 ◦C to prevent normal tissues frombeing affected. The 4.3-mg/mL sample satisfies theseconditions.

The heat generated by magnetic nanoparticles underan alternating magnetic field increases the temperatureof the constituents in the sample. The relationship be-tween the heat and the temperature increases is given by

Fig. 6. (Color online) Effects of concentration on the sat-uration temperature and the initial temperature rise.

ΔQ = mW cW ΔT + mPEGcPEGΔT + mNicNiΔT

+mFecFeΔT. (1)

In the above equation, ΔT is the temperature change ofthe sample and cW , cPEG, cNi, and cFe are the specificheats of water, PEG, nickel, and iron, respectively. Ad-ditionally, mW , mPEG, mNi, and mFe are the masses ofwater (1 mL), PEG, nickel, and iron, respectively.

The SAR is defined as the dissipation heat generatedby a unit mass of magnetic nanoparticles and is given by[19,20].

SAR =ΔQ/ΔT

mNi + mFe

=ΔT/Δt

mNi + mFe

[mW cW

+ mPEGcPEG + mNicNi + mFecFe]

∼= mW cW

mNi + mFe

(ΔT

Δt

). (2)

Here, ΔTΔt is the initial rate of temperature increase. In

order to simplify Eq. (2), we applied the fact that themass of water (1 g) in the sample is much larger thanthat of the other constituents (about 30 mg). Addi-tionally, the specific heat of water (cW = 4.2 J/g◦C)is also larger than those of the other constituents, i.e.,cPEG = 2.1 J/g◦C, cNi = 0.44 J/g◦C and cFe = 0.45J/g◦C. Thus, the heat required to increase the tempera-ture of the coated nanoparticles is much lower than thatrequired to increase the temperature of the water in thesample.

The SARs for the 8.7-, 6.5-, 4.3-, 3.2-, and 2.2-mg/mLsamples were calculated to be 17.32, 19.6, 22.8, 25.27,and 30.44 W/g, respectively. The decrease in the valueof the SAR with increasing particle concentration is dueto the increase in the dipolar magnetic moment with in-creasing particle concentration, which affects the Neelrelaxation time. The initial rates of temperature rise

Control of the Saturation Temperature in Magnetic Heating · · · – Yousaf Iqbal et al. -591-

Fig. 7. (Color online) Effect of concentration on the SAR(specific absorption rate) of the nanoparticles.

and the saturation temperatures for different nanoparti-cle concentrations are shown in Fig. 6, while the depen-dence of the SAR on the nanoparticle concentration isshown in Fig. 7.

The saturation temperatures of the 8.7- and 6.5-mg/mL samples were greater than 42 ◦C, which is thetemperature required for magnetic hyperthermia [21].On the other hand, the temperatures of the 3.2- and2.2-mg/mL samples did not reach 42 ◦C. As stated pre-viously, in magnetic hyperthermia applications, the tem-perature should be regulated at 42 ◦C in order to preventthe normal tissues from burning. We already observedin Fig. 5 that for a given magnetic field strength, thesaturation temperature could be controlled by changingthe concentration of nanoparticles in the sample. How-ever, we can also control the saturation temperature ofthe sample for a given concentration of nanoparticles bychanging the magnetic field strength. For the 3.2- and2.2-mg/mL samples, if a higher field strength is used, thesaturation temperature will increase up to 42 ◦C. On theother hand, the saturation temperatures of the 8.7- and6.5-mg/mL samples can be regulated at 42 ◦C by usinga smaller field strength. One such example is shown inFig. 8, which demonstrates that the saturation temper-ature of the 8.7-mg/mL sample can be lowered to 42 ◦Cby using a lower field intensity of 3.9 kA/m.

The calorimetric method has been used to correlatethe heating and cooling curves with the temperature-dependent magnetization for the dispersion of magneticnanoparticles under an alternating magnetic field. If theheating measurements were carried out using a nanopar-ticle dispersion and the temperature is restricted to theboiling point of the liquid medium (100 ◦C for water),the extrapolation method can be applied to obtain en-ergy absorption up to the Curie temperature of the mag-netic nanoparticles, which is above the boiling point ofthe liquid medium [22].

The total power dissipation behavior of the magnetic

Fig. 8. (Color online) Dependence of magnetic heating onthe field intensity for the 8.7-mg/mL sample. The sampleshows a saturation temperature of 42 ◦C at a field strengthof 3.9 kA/m.

nanoparticles near the Curie temperature can be de-scribed by

P ∼ (TC − T )TC

[1 +

(TC − T )TC

+TB

TC+ ϑ

((TC − T )

TC

)2

+ϑ

(TB

TC

)2

+ . . .

]. (3)

From the calorimetric perspective, the total power dissi-pation can also be expressed as

P = ρfC

[(dT

dt

)heating

−(

dT

dt

)cooling

]. (4)

Here, ρf is the magnetic fluid’s density, C is its specificheat, and dT/dt is the rate of temperature change. FromEq. (4), the difference between the heating and coolingrates at a given temperature T is clearly proportional toTc−T. In other words, the two processes should intersectat T = Tc. As a result, we obtain the intersection pointby extrapolating the two processes. The temperatureat the intersection point can be identified as the Curietemperature.

Using the above method, we estimated the Curie tem-perature of the nickel-ferrite nanoparticles by using theheating and cooling curves. The heating and coolingcurves are shown in Fig. 9. The Curie temperature canbe identified as the temperature corresponding to the in-tersection of the heating and cooling rate curves, and thisis shown in Fig. 10. The Curie temperature of the nickel-ferrite nanoparticles was found to be 495 ◦C, which ismuch smaller than that measured for bulk nickel ferrite(570 ◦C) [23].

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Fig. 9. (Color online) Heating and cooling curve for the8.7-mg/mL sample.

Fig. 10. (Color online) Curie temperature of the coatedsample obtained by extrapolating the rates of temperaturechange during the heating and cooling processes. The Curietemperature is identified as the temperature correspondingto the cross point of the heating and cooling rate curves.

IV. CONCLUSION

Sustainable heating of nanoparticles with the temper-ature controlled at 42 ◦C for at least 30 min is necessaryfor magnetic hyperthermia applications. We succeededin controlling the temperature at 42 ◦C in aqueous so-lutions of PEG-coated nickel ferrites by applying an ACmagnetic field with a field strength of 5.5 kA/m at 260kHz. The concentration of nanoparticles for this sam-ple was 4.3 mg/mL. We also noticed that the satura-tion temperature of the samples could be increased or

decreased to 42 ◦C by increasing or decreasing the fieldstrength, respectively. For example, the 8.7-mg/mL sam-ple showed a saturation temperature of 42 ◦C for a lowerfield strength of 3.9 kA/m. The Curie temperature ofthe coated nanoparticles was measured to be 495 ◦C.These results show the applicability of the PEG-coatednickel-ferrite nanoparticles to controlled magnetic hyper-thermia.

ACKNOWLEDGMENTS

This work was supported by the National ResearchFoundation of Korea (2010-0021315).

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