Exchange-Coupled Fe3O4/CoFe2O4 Nanoparticles for Advanced Magnetic Hyperthermia

We report a systematic study of the effects of core and shell size on the magnetic properties and heating efficiency of exchange-coupled Fe3O4/CoFe2O4 core/shell nanoparticles. The nanoparticles were synthesized using thermal decomposition of organometallic precursors. Transmission electron microscopy (TEM) confirmed the formation of spherical Fe3O4 and Fe3O4/CoFe2O4 nanoparticles. Magnetic measurements showed high saturation magnetization for the nanoparticles at room temperature. Increasing core diameter (6.4±0.7, 7.8±0.1, 9.6±1.2 nm) and/or shell thickness (∼1, 2, 4 nm) increased the coercive field (HC), while an optimal value of saturation magnetization (MS) was achieved for the Fe3O4 (7.8±0.1nm)/CoFe2O4 (2.1±0.1nm) nanoparticles. Magnetic hyperthermia measurements indicated a large increase in specific absorption rate (SAR) for 8.2±1.1 nm Fe3O4/CoFe2O4 compared to Fe3O4 nanoparticles of same size. The SAR of the Fe3O4/CoFe2O4 nanoparticles increased from 199 to 461 W/g for 800 Oe as the thickness of ...


I. INTRODUCTION
Cancer has become one of the most common causes of death in our society, becoming the second leading cause of death in the USA. 1 For this reason, there is a pressing need to improve and find new supplementary ways for cancer treatments that are less toxic than chemotherapy and relatively easy to administer to patients. Magnetic hyperthermia has emerged as a promising candidate for cancer treatment. 2,3 By subjecting magnetic nanoparticles to DC and AC magnetic fields, the location of a tumor can be targeted and doses of heat can be delivered to the cancer cells, respectively, without damaging the surrounding healthy tissues. 2,3 In order to implement this treatment, small concentrations of nanoparticles with high heating efficiency are desired. 4,5 For biomedical applications, iron oxide nanoparticles are commonly used due to their intrinsic biocompatibility. 6,7 In particular, Fe 3 O 4 and γ-Fe 2 O 3 nanoparticles have been extensively studied for magnetic hyperthermia because of their tunable magnetic properties and stable suspension in the superparamagnetic regime. However, their relatively low heating capacity or small specific absorption rate (SAR) makes them less desirable for practical applications. 8,9 It has been shown that the SAR of magnetic nanoparticles can be tuned by varying particle size, saturation magnetization, and effective anisotropy. 6,7,10,11 Recently, a large improvement in SAR has been reported in exchange-coupled nanoparticles with exchange coupling between soft and hard magnetic phases. 12 heating efficiency and the effect of core diameter and shell thickness on the heating efficiency in these systems have remained unclear and unexplored.
In the present study, we report how the variations in the core diameter and shell thickness affect the magnetic response and heating efficiency of exchange-coupled Fe 3 O 4 /CoFe 2 O 4 core/shell nanoparticles.

II. EXPERIMENT
Fe 3 O 4 @CoFe 2 O 4 nanoparticles of varying core diameter (6.4±0.7, 7.8±0.1, 9.6±1.2 nm) and shell thickness (∼1 nm, 2 nm, and 4 nm) were prepared by seed mediated thermal decomposition of organometallic precursors in the presence of oleic acid, oleylamine, 1-2, hexadecanediol, and benzyl ether. The details of the synthesis process are described elsewhere. 14,15 A Bruker AXS D8 X-ray diffractometer (XRD) was used to analyze the crystalline structure of the nanoparticles. Transmission electron microscopy (TEM, FEI Morgagni 268, 60kV) was performed in order to obtain the shape and size distribution of the nanoparticles. The magnetic properties of the nanoparticles were measured using a Physical Property Measurement System (PPMS) from Quantum Design, with a vibrating sample magnetometer insert. Magnetic hysteresis (M-H) loops were performed at 300K with applied fields ranging from -50 to 50 kOe. Saturation magnetization of the particle samples was normalized by the mass of the dried particles used for the measurement. The contribution of surfactant mass to the final mass of the dried particles is not significant to change the accuracy of the saturation magnetization. AC magnetic hyperthermia experiments were carried out using a 4.2 kW Ambrell Easyheat LI 3542 system. The frequency was fixed at 310 kHz and the amplitude of the magnetic field was adjusted from 400 to 800 Oe. During the hyperthermia experiments, the particles were dispersed in hexane with a concentration of 1mg/ml. Figure 1 shows the TEM images of Fe 3 O 4 cores and Fe 3 O 4 /CoFe 2 O 4 core/shell nanoparticles. From TEM, the nanoparticles are observed to have a roughly spherical shape. As mentioned above, the Fe 3 O 4 /CoFe 2 O 4 nanoparticles were obtained using a seed mediated thermal decomposition process. In this process, a Fe 3 O 4 seed nanoparticle was used as a template in order to grow the CoFe 2 O 4 shell. To obtain various shell thicknesses, the previous synthesis process was repeated using the core/shell nanoparticle as a seed. Using this synthesis method, we observed an increment in the nanoparticle size by ∼2 nm, excluding the case for Figure 1(f) where we saw an increment of ∼4 nm ( Table I). The thickness of the shell was determined by measuring the particles size before and after the seed-mediated shell growth.

III. RESULTS AND DISCUSSION
XRD measurements were performed to confirm the composition and crystal structure of the nanoparticles. Figure 2 shows the XRD patterns for the 6.4±0.7 nm Fe 3 O 4 core and the 6.4±0.7 nm/ 0.9±0.5 nm Fe 3 O 4 /CoFe 2 O 4 core/shell nanoparticles. The XRD patterns possess six distinctive peaks for Fe 3 O 4 and CoFe 2 O 4 nanoparticles. The peak positions correspond to the cubic structure of an iron phase that can be either magnetite or maghemite. 16 Here we note that XRD alone is not a conclusive tool to distinguish between Fe 3 O 4 and CoFe 2 O 4 phases due to their similar structure.
Magnetic measurements were performed on the nanoparticles to understand their magnetic properties and effects on the heating efficiency. It is well known that there is a correlation between the heating efficiency and the saturation magnetization of the nanoparticles. 17 All the measurements were conducted at room temperature (same temperature as hyperthermia measurements). In order to see how the magnetization evolves in the core/shell system, hysteresis loops were taken for various core diameters and shell thicknesses. Figure 3(a) shows the M-H loops for different core/shell systems, where the core diameter remained the same (7.8±0.1 nm) and the shell thickness was varied from ∼1 to 4 nm. It can be seen from Figure 3(a) that the saturation magnetization (M S ) increases as the CoFe 3 O 4 shell thickness increases, until a critical thickness (2.1±0.1 nm) is reached. On the other hand, when the core diameter was varied from 6.4±0.7 to 9.6±1.2 nm and the shell thickness remained the same (∼1 nm), M S remained constant until the diameter of the core reached 7.8±0.1 nm, above which we observed an increase in M S (see Figure 3(b)). In the case where the shell thickness was varied, the highest M S (∼83 emu/g) obtained corresponds to the ∼2 nm shell thickness, while for the ∼1 nm and ∼4 nm shell systems, M S remained at ∼68 emu/g. For the case where the core diameter was varied, however, the highest M S (∼76 emu/g) was obtained for the system with a core diameter  The heating efficiency of the nanoparticles was calculated using the specific absorption rate (SAR), which is expressed as follows: where C p is the specific heat of the solution, m s the mass of the solution, m n the mass of the nanoparticles, and ∆T /∆t is the initial slope of the heating curve. Figure 4 shows SAR vs. field for the core/shell nanoparticles with various core diameters and shell thicknesses. As can be observed, SAR increased with increasing the AC magnetic field, except for the 7  increases in coercive field, H C (Table I) and effective magnetic anisotropy, H K . 18 It is worth mentioning that the increase in the SAR value is greater for the variation of the shell thickness than the variation in the core diameter. From these observations, we can infer that the increase in SAR is governed largely by the shell thickness in these nanoparticles.  16,19 The magnetic and hyperthermia parameters of the samples are summarized in Table I.

IV. CONCLUSIONS
We have successfully synthesized Fe 3 O 4 /CoFe 2 O 4 core/shell nanoparticles with different core diameters and shell thicknesses. We have studied how the magnetic properties and heating efficiency change when the core and shell sizes are varied and performed a comparative analysis. Our work shows the ability to tune the saturation magnetization and magnetic anisotropy, thus improving the heating efficiency. The results indicate that the variation in the shell thickness has a greater impact on the magnetic response and heating efficiency compared to the variation in the core size in the