Control of the Saturation Temperature in Magnetic Heating by Using Polyethylene-glycol-coated Rod-shaped Nickel-ferrite (NiFe 2 O 4 ) Nanoparticles

Journal of the Korean Physical Society, Vol. 68, No. 4, February 2016, pp. 587 592 Control of the Saturation Temperature in Magnetic Heating by Using Polyethylene-glycol-coated Rod-shaped Nickel-ferrite (NiFe 2 O 4 ) 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 hyperthermia applications by using the co-precipitation method. The PEG coating occurred during the synthesis of the nanoparticles. The coated nanoparticles were rod-shaped with an average length of 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-transform infrared spectra. The nanoparticles exhibited superparamagnetic characteristics with negligible coercive force. Further, magnetic heating effects were observed in aqueous solutions of the coated nanoparticles. The saturation temperature could be controlled at 42 C by changing the concentration of the nanoparticles in the aqueous solution. Alternately, the saturation temperature could be controlled for a given concentration of nanoparticles by changing the intensity of the magnetic field. The Curie temperature of the nanoparticles was estimated to be 495 C. These results for the PEG-coated nickel-ferrite nanoparticles showed the possibility of utilizing them for controlled magnetic hyperthermia at 42 C. PACS numbers: 81.05.Ni, 76.60.Es, 61.46.Df, 87.61.-c Keywords: Nickel-ferrite nanoparticles, Saturation temperature, Polyethylene-glycol coating, Curie temperature DOI: 10.3938/jkps.68.587 I. INTRODUCTION Nanoparticles have attracted great attention, owing to their characteristic chemical, optical, electrical, mechanical, and magnetic properties that are different from those of the corresponding bulk systems [1 3]. These peculiar properties originate from their high reactivity with other materials due to their large surface area to volume ratio as well as their quantum size effects. The high reactivity of the nanoparticles is utilized in nanoparticle catalysis, nano drug delivery, and improvement of wear resistance. On the other hand, the peculiar optical and electrical properties of nanoparticles that have a size smaller than theelectron sdebrogliewavelengtharedifferentfrom those of bulk systems owing to the quantum size effects. In addition, quantum confinement causes transparency of titanium-oxide nanoparticles, block of ultraviolet in antimony-tin-oxide nanoparticles, and changes in the fluorescence with particle size for gold nanoparticles [4 6]. Nanostructures can exist various forms, including liposomes, polymeric micelles, dendrimers, nanoparticles, E-mail: ilrhee@knu.ac.kr nanocapsules, and carbon nanotubes [7]. Among those nanostructures, nanoparticles of various materials and shapes have been investigated from the point of view of utilizing them in biomedical applications. In particular, magnetic nanoparticles are useful for both the diagnosis and the treatment of diseases owing to their magnetic properties. In addition, magnetic nanoparticles are useful as carriers in nano-drug delivery systems owing to the possibility of tracing the systems with magnetic resonance imaging (MRI). Various magnetic nanoparticles are being used as MRI contrast agents. In addition, magnetic nanoparticles can be utilized for the internal magnetic hyperthermia treatment of cancer. In the magnetic hyperthermia treatment procedure, the magnetic nanoparticles are used as heat generators under an alternating magnetic field, and the difference in the heat resistance between normal and cancer cells is exploited for treatment. Magnetic nanoparticles are toxic; therefore, surface modification of the nanoparticles is required in order to apply them to the human body. Surface modification is also required for labeling various chemicals such as drugs and targeting ligands on their surfaces. Vari- -587-

-588- Journal of the Korean Physical Society, Vol. 68, No. 4, February 2016 ous biocompatible materials are used for surface modification, including polyethylene glycol (PEG), chitosan, dextran, carbon, gold, and oleic acid [8 13]. In the current study, rod-shaped nickel-ferrite nanoparticles were prepared for magnetic hyperthermia applications. The nanoparticles were coated with PEG to achieve biocompatibility. The superparamagnetic properties of these nanoparticles were confirmed by using a vibrating sample magnetometer (VSM). Aqueous solutions containing coated nanoparticles in various concentrations were prepared for checking the magnetic heating effect. In addition, the dependence of the specific absorption rate (SAR) on the concentration of nanoparticles was observed. The dependence of the intensity of heating on the nanoparticle concentration was also examined. II. EXPERIMENTS Bivalent metals (M 2+,whereM=Fe,Co,Mn,Ni,etc.) and trivalent Fe 3+ ions can be co-precipitated from their aqueous salt solutions by adding alkaline solutions such as NH 4 OH and NaOH to the salt solutions. In this study, we used the co-precipitation method for formulating the nickel-ferrite nanoparticles. The surfaces of the particles were coated during the synthesis of the nanoparticles themselves [10, 14]. In brief, 3 ml of an aqueous solution of 0.3-M NiCl 2 4H 2 O was first mixed with 3 ml of an aqueous solution of 0.6-M FeCl 3 6H 2 O. Following this, 6 ml of 2% (w/w) PEG solution was added to this mixture in a 250-mL double-walled beaker. The temperature of the water circulating across the double-walled beaker was maintained at 4 C. Air bubbles were introduced into this mixture for 1 h by using a pipette. As the nanoparticles were formed, PEG adhered to their surfacesataphofaround7. ToachievethispH,wehad added 1% (v/v) NaOH drop-wise to the metal salt - PEG solution mixture at a rate of 1 ml/min. For stabilization of the nanoparticles, the final solution was placed in an ultrasonic environment for 10 h, following which the solution was filtered using a 100-nm filter. The size of the nanoparticle depends on the ultrasonic treatment time because ultrasonic treatment provides energy to dissociate the excess PEG from the coated particles. Powder samples of the coated nanoparticles were obtained by keeping the wet particles at 35 C in air for about 12 days. Aqueous solutions of the nickel-ferrite nanoparticles were prepared for investigating the heating effect of the magnetic nanoparticles under an alternating magnetic field. A powder sample of the PEG-coated nickel-ferrite nanoparticles (20 mg) was dispersed in 50 ml of deionized water by means of ultrasonication for 20 min. The dispersion was kept in air for 6 to 10 days, allowing the uncoated nanoparticles to precipitate to the bottom. The upper solution was then collected carefully by using a 50-mL syringe. The resultant dispersion was observed to be highly stable for months. This dispersion of nickelferrite nanoparticles was very dilute. A concentrated sample was obtained by placing the dilute solution in a vacuum oven at 40 C for about 5 days. The amounts of nickel and iron in the aqueous solution were measured by using inductively coupled plasma (ICP) spectrometry. Four additional samples were prepared by diluting the concentrated sample to 75%, 50%, 37.5%, and 25% in order to measure the effect of concentration on the magnetic heating effect. The morphology and the particle size distribution of the nickel-ferrite nanoparticles were analyzed using transmission electron microscopy (TEM; H-7600, Hitachi Ltd.). The bonding of PEG on the surface of the nanoparticles was confirmed using Fourier transform infrared spectroscopy (FTIR; Nicolet 380, Thermo Scientific USA). The magnetic measurements were carried out using VSM (MPMS, Quantum Design). The chemical composition and concentration of the coated nanoparticles in the aqueous solution were measured using ICP spectrometery (Thermo Jarrell Ash IRISAP). Further, the magnetic heating effects of the nanoparticles dispersed in water were measured using an induction heating system (Osung High Tech, OSH-120-B). The temperature of the solution was measured with a CALEX infrared thermometer (PyroUSB CF, Calex Electronics Limited). III. RESULTS AND DISCUSSION Figure 1 shows a TEM image of the coated nickelferrite nanoparticles. The PEG-coated nanoparticles are rod-shaped with a uniform size distribution, an average length of 16 nm and an average diameter of 4.5 nm. The size distributions of one hundred nanoparticles obtained from a TEM image are shown in the histogram in Fig. 1. Figure 2 shows the hysteresis curve of the PEG-coated nickel-ferrite nanoparticles at room temperature. From the figure in the inset, the zero remanence and coercivity are apparent, indicating that the nanoparticles exhibit superparamagnetic properties at room temperature. The superparamagnetic behavior is desirable for biomedical applications because superparamagnetic nanoparticles exhibit magnetic behavior only under the influence of external magnetic fields. The FTIR spectra of PEG-coated nickel-ferrite nanoparticles are shown in Fig. 3. Two absorption bands at 640 and 470 cm 1 are observed due to the metaloxygen stretching vibrations at the tetrahedral and octahedral sites, respectively [15]. The absorption band at 1,100 cm 1 corresponds to the stretching of the C O C bonding in the CH 2 O CH 2 group of PEG [16,17]. On the other hand, the absorption bands at 3,410 and 1,630 cm 1 are attributed to the stretching and vibra-

Control of the Saturation Temperature in Magnetic Heating Yousaf Iqbal et al. -589- Fig. 3. (Color online) FTIR spectra for the coated nanoparticles. Fig. 4. Schematic of the induction heating system. Fig. 1. (Color online) TEM image and size distribution of the nanoparticles. The histograms show the length and width distributions of one hundred nanoparticles obtained from the TEM image. Fig. 2. (Color online) Hysteresis curve for a powder sample of the coated nanoparticles. The figure in the inset indicates a negligible coercive force. tion of the O H bond, respectively. Further, the absorption bands at 2,870, 1,400, 1,250, and 950 cm 1 are due to symmetric stretching, scissoring (in-plane bending), twisting stretching, and out-of-plane bending vibration of the C H bond, respectively [17]. These results clearly confirm the bonding of PEG on the surfaces of the nickelferrite nanoparticles. The amounts of nickel and iron in the concentrated aqueous solution were measured by ICP spectrometry to be 2,452 and 6,273 mg/l, respectively. The atomic ratio of iron to nickel is 2.17, which is approximately consistent with the chemical formula of NiFe 2 O 4.Aswe stated previously, four additional samples were prepared by diluting the concentrated sample to 75%, 50%, 37.5%, and 25%. While the nanoparticle concentration in the concentrated sample was 8.7 mg/ml, the nanoparticle concentrations in the 75%, 50%, 37.5%, and 25% diluted samples were 6.5, 4.3, 3.2, and 2.2 mg/ml, respectively. A schematic figure of the induction heating system used for observing the magnetic heating effects is shown in Fig. 4. Aqueous samples of the nanoparticles were placed in the RF coil with a resonance frequency of 260 khz. Field strengths of 2.3, 3.9, and 5.5 ka/m were used to observe the effect of the field strength on the magnetic heating effect. An IR thermometer located 10 cm above the sample was used to measure the temperature of the sample. When a magnetic system is subjected to an alternating magnetic field, heat is generated due to certain loss mechanisms, which can be classified as hysteresis and relaxation loss [18]. The latter can be further divided into Néel and Brown losses. Because the superparamagnetic nanoparticles in our case show no hysteresis, as

-590- Journal of the Korean Physical Society, Vol. 68, No. 4, February 2016 Fig. 5. (Color online) Effect of concentration on magnetic heating. The 4.3-mg/mL sample shows a saturation temperature of 42 C. Fig. 6. (Color online) Effects of concentration on the saturation temperature and the initial temperature rise. indicated in Fig. 2, we can neglect the hysteresis losses. Ferromagnetic resonance loss can also be ignored in the present study because it occurs in the GHz frequency range, which is much larger than the 200 300 khz frequency range used in this study. Thus, the remaining heating mechanisms for the nanoparticles are Néel and Brown losses. The background heating effects caused by pure water and the sample container were estimated and were observed to be negligible. Aqueous samples (1 ml) taken in thermally-insulated containers were placed under an alternating magnetic field. The increase in the temperature as a function of the heating time for five samples with different concentrations of nickel-ferrite nanoparticles are shown in Fig. 5. The magnetic field intensity was fixed at 5.5 ka/m with a frequency of 260 khz. We can see from Fig. 5 that the temperature of the concentrated sample increases faster than that of the diluted samples. This dependence of the temperature rise on the concentration of nanoparticles is expected because more heat generators (nanoparticles) are present in the concentrated sample. All the samples are also observed to reach saturation temperatures after about 1,000 s. At this time, heat generation is balanced by heat loss. The saturation temperatures for the 8.7-, 6.5-, 4.3-, 3.2-, and 2.2-mg/mL samples were 48, 45, 42, 41, and 39 C, respectively. During the magnetic hyperthermia treatment, the temperature should be maintained at 42 C for 30 min to kill the malignant tissues. At the same time, the temperature should also be kept below 46 C to prevent normal tissues from being affected. The 4.3-mg/mL sample satisfies these conditions. The heat generated by magnetic nanoparticles under an alternating magnetic field increases the temperature of the constituents in the sample. The relationship between the heat and the temperature increases is given by ΔQ = m W c W ΔT + m PEG c PEG ΔT + m Ni c Ni ΔT +m Fe c Fe ΔT. (1) In the above equation, ΔT is the temperature change of thesampleandc W, c PEG, c Ni,andc Fe are the specific heats of water, PEG, nickel, and iron, respectively. Additionally, m W, m PEG, m Ni,andm Fe are the masses of water (1 ml), PEG, nickel, and iron, respectively. The SAR is defined as the dissipation heat generated by a unit mass of magnetic nanoparticles and is given by [19,20]. SAR = ΔQ/ΔT = ΔT/Δt [m W c W m Ni + m Fe m Ni + m Fe + m PEG c PEG + m Ni c Ni + m Fe c Fe ] ( ) m W c W ΔT =. (2) m Ni + m Fe Δt Here, ΔT Δt is the initial rate of temperature increase. In order to simplify Eq. (2), we applied the fact that the mass of water (1 g) in the sample is much larger than that of the other constituents (about 30 mg). Additionally, the specific heat of water (c W =4.2J/g C) is also larger than those of the other constituents, i.e., c PEG =2.1J/g C, c Ni =0.44J/g Candc Fe =0.45 J/g C. Thus, the heat required to increase the temperature of the coated nanoparticles is much lower than that required to increase the temperature of the water in the sample. The SARs for the 8.7-, 6.5-, 4.3-, 3.2-, and 2.2-mg/mL samples were calculated to be 17.32, 19.6, 22.8, 25.27, and 30.44 W/g, respectively. The decrease in the value of the SAR with increasing particle concentration is due to the increase in the dipolar magnetic moment with increasing particle concentration, which affects the Néel relaxation 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 nanoparticle concentrations are shown in Fig. 6, while the dependence of the SAR on the nanoparticle concentration is showninfig.7. The saturation temperatures of the 8.7- and 6.5- mg/ml samples were greater than 42 C, which is the temperature required for magnetic hyperthermia [21]. On the other hand, the temperatures of the 3.2- and 2.2-mg/mL samples did not reach 42 C. As stated previously, in magnetic hyperthermia applications, the temperature should be regulated at 42 C in order to prevent the normal tissues from burning. We already observed in Fig. 5 that for a given magnetic field strength, the saturation temperature could be controlled by changing the concentration of nanoparticles in the sample. However, we can also control the saturation temperature of the sample for a given concentration of nanoparticles by changing the magnetic field strength. For the 3.2- and 2.2-mg/mL samples, if a higher field strength is used, the saturation temperature will increase up to 42 C. On the other hand, the saturation temperatures of the 8.7- and 6.5-mg/mL samples can be regulated at 42 Cbyusing a smaller field strength. One such example is shown in Fig. 8, which demonstrates that the saturation temperature of the 8.7-mg/mL sample can be lowered to 42 C by using a lower field intensity of 3.9 ka/m. The calorimetric method has been used to correlate the heating and cooling curves with the temperaturedependent magnetization for the dispersion of magnetic nanoparticles under an alternating magnetic field. If the heating measurements were carried out using a nanoparticle dispersion and the temperature is restricted to the boiling point of the liquid medium (100 C for water), the extrapolation method can be applied to obtain energy absorption up to the Curie temperature of the magnetic nanoparticles, which is above the boiling point of the liquid medium [22]. The total power dissipation behavior of the magnetic Fig. 8. (Color online) Dependence of magnetic heating on the field intensity for the 8.7-mg/mL sample. The sample shows a saturation temperature of 42 C at a field strength of 3.9 ka/m. nanoparticles near the Curie temperature can be described by P (T [ C T ) 1+ (T C T ) + T ( ) 2 B (TC T ) + ϑ T C T C T C T C ( ) 2 TB +ϑ +...]. (3) From the calorimetric perspective, the total power dissipation can also be expressed as [ (dt ) ( ) ] dt P = ρ f C. (4) dt heating dt cooling Here, ρ f is the magnetic fluid s density, C is its specific heat, and dt/dt is the rate of temperature change. From Eq. (4), the difference between the heating and cooling rates at a given temperature T is clearly proportional to T c T. In other words, the two processes should intersect at T = T c. As a result, we obtain the intersection point by extrapolating the two processes. The temperature at the intersection point can be identified as the Curie temperature. Using the above method, we estimated the Curie temperature of the nickel-ferrite nanoparticles by using the heating and cooling curves. The heating and cooling curves are shown in Fig. 9. The Curie temperature can be identified as the temperature corresponding to the intersection of the heating and cooling rate curves, and this is shown in Fig. 10. The Curie temperature of the nickelferrite nanoparticles was found to be 495 C, which is much smaller than that measured for bulk nickel ferrite (570 C) [23]. T C

-592- Journal of the Korean Physical Society, Vol. 68, No. 4, February 2016 decreased to 42 C by increasing or decreasing the field strength, respectively. For example, the 8.7-mg/mL sample showed a saturation temperature of 42 Cforalower field strength of 3.9 ka/m. The Curie temperature of the coated nanoparticles was measured to be 495 C. These results show the applicability of the PEG-coated nickel-ferrite nanoparticles to controlled magnetic hyperthermia. ACKNOWLEDGMENTS This work was supported by the National Research Foundation of Korea (2010-0021315). Fig. 9. (Color online) Heating and cooling curve for the 8.7-mg/mL sample. REFERENCES Fig. 10. (Color online) Curie temperature of the coated sample obtained by extrapolating the rates of temperature change during the heating and cooling processes. The Curie temperature is identified as the temperature corresponding to the cross point of the heating and cooling rate curves. IV. CONCLUSION Sustainable heating of nanoparticles with the temperature controlled at 42 C for at least 30 min is necessary for magnetic hyperthermia applications. We succeeded in controlling the temperature at 42 Cinaqueoussolutions of PEG-coated nickel ferrites by applying an AC magnetic field with a field strength of 5.5 ka/m at 260 khz. The concentration of nanoparticles for this sample was 4.3 mg/ml. We also noticed that the saturation temperature of the samples could be increased or [1]A.K.Singh,Adv.PowderTech.21, 609 (2010). [2] M. Horie et al., Metallomics 4, 350 (2012). [3] D. Guo, G. Xie and J. Luo, J. Phys. D: Appl. Phys. 47, 013001 (2014). [4] M. De, P. S. Ghosh and V. M. Rotello, Adv. Mater. 20, 4225 (2008). [5] A. Kaur and U. Gupta, J. Mater. Chem. 19, 8279 (2009). [6] O. Bichler et al., IEEE Trans. Elec. Dev. 57, 3115 (2010). [7] I. Rhee, New Physics: Sae Mulli 65, 411 (2015). [8] T. Ahmad et al., Curr. Appl. Phys. 12, 969 (2012). [9] A. Guerrero-Martínez, J. Pérez-Juste and L. M. Liz- Marzán,Adv.Mater.22, 1182 (2010). [10] T. Ahmad et al., J. Magn. Magn. Mater. 381, 151 (2015). [11] H. Bae et al., Nanoscale Res. Lett. 7, 44 (2012). [12] T. Ahmad et al., J. Nanosci. Nanotechnol. 12, 5132 (2012). [13] A. Senpan et al., ACSNano3, 3917 (2009). [14] T. Ahmad, I. Rhee, S. Hong, Y. Chang and J. Lee, J. Nanosci. Nanotechnol. 11, 5645 (2011). [15] T. Ahmad, Y. Iqbal, H. Bae, I. Rhee, S. Hong, Y. Chang and J. Lee, J. Korean Phys. Soc. 62, 1696 (2013). [16] A. Mukhopadhyay, N. Joshi, K. Chattopadhyay and G. De, ACS Appl. Mater. Interfaces 4, 142 (2012). [17]L.Khanna,N.K.Verma,Phys.B427, 68 (2013). [18] R. Hergt, S. Dutz, R. Müller and M. Zeisberger, J. Phys.: Condens. Matter. 18, S2919 (2006). [19] S. Laurent, S. Dutz, U. O. Häfeli and M. Mahmoudi, Adv. Colloid Interface Sci. 166, 8 (2011). [20] A. S. Teja and P.-Y. Koh, Prog. Cryst. Growth Charact. Mater. 55, 22 (2009). [21] A. Jordan et al., J. Magn. Magn. Mater. 194, 185 (1999). [22] V. Nica, H. M. Sauer, J. Embs and R. Hempelmann, J. Physics: Condens. Matter 20, 204115 (2008). [23] M. V. Kuznetsov, Y. G. Morozov and O. V. Belousova, Inorg. Mater. 48, 1044 (2012).