This study focuses on the synthesis and characterization of a magnetic nanomaterial used in magnetic hyperthermia. Cerium gadolinium zinc-iron (CeGdZnFe) magnetic nanoparticles were synthesized by a coprecipitation method for application as magnetic hyperthermia agents. Determination of phase purity and their identification was achieved by X-ray diffraction studies using a Phillips powder diffractometer with Cu Kα radiation. Typical TEM micrographs of the dispersion of CeGdZn-ferrite nanoparticles and CeGdZn-ferrite PEG-encapsulated nanoparticles in ethanol deposited over a Cu grid were taken as part of the characterization techniques to be used for newly developed materials. It was then fitted by a Gaussian distribution with mean diameter dm ±1.0 nm. The investigation of magnetic properties showed that adjusting, Gd and Zn contributes to the nanoparticles added to the adjustment of all magnetic properties of CeGdZnFe.
Various studies have highlighted the colloidal nanoparticle synthesis advancement, which has enabled the implementation of various high-quality nanoparticles for treatment of various patients [
Initially, the magnetic particle hyperthermia heating treatment using magnetic nanoparticles was brought forward by Gilchrist et al. in 1957, which continued to be an active area of cancer research [
Magnetic hyperthermia supplies heat at the tumor site by application of an external alternating magnetic field to the nanomagnetic particles. The particles then heat up and conduct that heat to the tumor cells. The materials’ use with the Curie temperature ranging from 41 to 46°C protects against overheating of normal cells, due to the decrease of magnetic coupling in the paramagnetic regime [
Magnetic nanoparticle materials have high specific power loss, and suitable temperature dependence of power loss is allowed by an adjustment of the Curie temperature to 43°C. One way to achieve this is through the use of magnetic nanoparticles with properties suitably modified by compositional variations. The most successful type which has been widely investigated consists of superparamagnetic iron oxide nanoparticles [
Hoque et al. [
In recent years, many studies have been focused on optimizing the heating efficiency in terms of nanoparticle intrinsic properties such as particle size, anisotropy constant, saturation magnetization, easy axis orientations, extrinsic properties such as AC field frequency, and amplitude and the role of dipolar interactions. Gadolinium and cerium present several of those characteristics. They are easy to produce; they present very small hydrodynamic diameters, and they are biodegradable. Cerium oxide nanoparticles with integrated gadolinium exhibit combined therapeutic capabilities. This type of nanomaterial is highly promising for applications in the fields of biomedical magnetic hyperthermia. Therefore, the present study has synthesized CeGdZn-ferrite nanoparticles using the chemical coprecipitation method in which the proportions of zinc and cerium were varied, and the effects on the properties have been studied. The self-heating temperature-rising characteristics of CeGdZn-ferrite nanoparticles obtained by the coprecipitation process were analysed under different applied magnetic fields and frequencies to confirm their effectiveness as hyperthermia agents. The Curie temperatures of their particles were ∼315 K.
The present study has reported on newly fabricated, as-synthesized, self-heating magnetic nanoparticles, known as CeGdZnFe in magnetic hyperthermia. The CeGdZnFe nanoparticle system showed both superparamagnetic and ferromagnetic behaviors depending on their particle sizes. Materials having large heating power generation per particle unit mass are mostly applicable for hyperthermia. Therefore, the study has developed various types of magnetic nanoparticles that are used as magnetic mediators. In recent years, many studies have been focused on optimizing the heating efficiency in terms of nanoparticle intrinsic properties such as particle size, anisotropy constant, saturation magnetization, easy axis orientations, extrinsic properties such as AC field frequency, and amplitude and the role of dipolar interactions. Gadolinium and cerium present several of those characteristics. They are easy to produce; they present very small hydrodynamic diameters, and they are biodegradable.
Chemicals were used for encapsulated magnetic particles. Magnetic nanoparticles that possess high magnetic susceptibility and saturation magnetization were suitable candidates for magnetic hyperthermia medical application. The phases of CeGdZnFe nanoparticles purchased separately from Chemicell were synthesized by coupling of chemical coprecipitation and ultrasonication. The particles were further coated with a cationic surfactant. Many particles were very well dispersed and were in the size range of 6–10 nm, as it is the case of as-synthesized CeGdZn-ferrites (Figure
Magnetic hyperthermia apparatus [
In this study, several CeGdZn-ferrite particles with various constituent proportions were synthesized to check the possibility of decreasing the Curie temperature to 315 K by adding Ce. Several samples of CeGdZnFe were synthesized using a chemical co-precipitation method. In this method, a 0.1 M solution of the metal salts GdCl2, Fe2SO4, CeCl3, and ZnSO4 was added to an 8 M solution of NaOH. The mixture was stirred vigorously at 90°C for 40 minutes. Thereafter, the synthesized magnetic nanoparticles were filtered and washed three times with distilled water and three times with acetone. The particles were then allowed to dry in air at room temperature.
The polymer emulsion method was used to encapsulate CeGdZn-ferrite nanoparticles inside ethyl cellulose (chemical), which has a glass transition temperature of 42°C. The ingredients used are listed in Table
Ingredients for ethyl cellulose-encapsulated CeGdZnFe using polymer emulsion.
Ingredients | Quantity |
---|---|
Polymer phase: ethyl cellulose | 2 gm |
Solvent: methylene chloride | 10 ml |
Aqueous medium phase: water | 40 ml |
Emulsifying agent: sodium dodecyl sulphate | 0.2 gm |
Inhibitor compound: 1-octanol | 0.5 ml, 0.4 gm |
Magnetic particles: CeGdZn-ferrite | 50 mg |
Magnetic particle: Polymer ratio | 1 : 40 (approximately) |
The sodium dodecyl sulphate and 1-octanol were dissolved in 40 ml of distilled water using a magnetic stirrer, and later 50 mg of CeGdZn-ferrite nanoparticles were added. The polymer phase was prepared by dissolving 2 gm of ethyl cellulose into 10 ml of methylene chloride. A crude emulsion was formed by adding the polymer phase to the medium aqueous phase. The crude emulsion was sonicated using an ultrasonicator five times in steps of 3 minutes. The resultant emulsion was then stirred inside a round bottom flask for 12 hours at 700 rpm. The solvent was then removed using a vacuum evaporation method. The polymer-encapsulated particles formed were washed with acetone and stored under the PBS buffer solution.
The apparatus used in estimating the magnetic heating depicted similarity to the coil devised by Jordan’s. The existence of a small difference in other setups prevented sample heating from the coil by running water through the coils. However, in this study, the foam and apparatus created a homogeneous alternating magnetic field within the coil, which in turn created E-fields in space perpendicular to the magnetic field at the center of the coil. X-ray diffraction is used to determine the identity of crystalline solids based on their atomic Plexiglas that prevented heat from transferring to the sample from the coil. Insulation also served to maintain heat within the sample to prevent excessive air cooling of the sample. This apparatus created a homogeneous alternating magnetic field within the coil, which in turn created E-fields in space perpendicular to the magnetic field at the center of the coil. X-ray diffraction is used to determine the identity of crystalline solids based on their atomic structure. During X-ray diffraction analysis, X-ray beams are reflected off the parallel atomic layers within the nanoparticle material over a range of diffraction angles.
Magnetic susceptibility is a dimensionless proportionality constant that describes the degree of magnetization of a material in response to the external magnetic field, it is the ratio of magnetization
Transmission electron microscopy (TEM) is used to characterize the morphology of materials such as nanoparticles. The samples are prepared for TEM imaging by inserting a TEM grid (copper coated with formvar) into a dry or wet powder. The powder is usually dried overnight using tweezers to hold the grid. The sample grid is then lightly tapped to remove any excess particles, and the grid is placed in the TEM for imaging. This procedure can be used to characterize the coated magnetic particles. TEM samples were prepared by placing a drop of the suspensions on a copper grid with a carbon membrane film. Images were taken using JEOL-2010 TEM operating up to 200 kV.
The DC SQUID magnetometer was used to characterize the magnetic properties of superparamagnetic nanoparticle systems. Using this device, ±5T DC fields can be applied to samples from 5 K to 400 K, with a sensitivity of 1 × 10−7 EMU in the detected moment. A SQUID is the most sensitive device available for measuring magnetic fields. It does not detect the magnetic field directly from the sample although the SQUID in the MPMS is the source of the instrument’s remarkable sensitivity. Instead, the sample moves through a system of superconducting detection coils, which are connected to the SQUID with superconducting wires allowing the current from the detection coils to inductively coupled to the SQUID sensor.
A major distinction between ferromagnets and paramagnets is that the ferromagnetic state is of the long-range order. This long-range order sets in at a phase transition, which occurs at the Curie temperature. The Curie temperature is close to the same point where a (1/
The physical properties of as-synthesized CeGdZn-ferrite nanoparticles were shown to depend on their size. Prepared nanoparticles demonstrated a certain polydispersity. It seemed interesting to compare the properties of small and large particles fractionated from the same polydisperse sample. The crystalline structure of the samples was identified from X-ray diffraction (XRD) patterns recorded in the 2
Powder X-ray diffraction pattern of and reference pattern for CeGdZn-ferrite magnetic nanoparticles. The pattern is representative for all the samples of the series.
Figure
Ethyl cellulose encapsulated CeGdZn-ferrite by polymer emulsion.
Table
Characteristics of the CeGdZn-ferrite inorganic nanoparticles used in experimentation.
Sample | Mean radius DXRD (nm) | Mean radius DTEM (nm) | Concentration per flask (g/mL) | Crystalline structure | Surface chemistry |
---|---|---|---|---|---|
1 | 15 ± 0.4 | 11 ± 0.4 | 3.303 × 10−2 | Crystalline | Hydrophilic |
2 | 13 ± 0.5 | 9 ± 0.5 | 2.180 × 10−3 | Crystalline | Hydrophilic |
3 | 10 ± 0.2 | 6 ± 0.7 | 1.130 × 10−4 | Crystalline | Hydrophilic |
4 | 8 ± 0.5 | 5 ± 0.2 | 3.201 × 10−2 | Crystalline | Hydrophilic |
The heating pattern for CeGdZn-ferrite magnetic nanoparticles is shown in Figure The likelihood of RF interference contributing to an apparent increase in temperature The inability to completely characterize heat-producing mechanisms in this specific experimental setting
CeGdZn-ferrite nanoparticles magnetization curve taken by SQUID at 5 K (a) and at 300 K (b).
Various procedures need to be attempted to show the contributions of the first reason by using the proper control materials. Also, the second reason has been discussed in terms of current research to help justify claims of more pronounced temperature rises in ferromagnetic materials.
From the hysteresis loop, primary magnetic properties, such as retentivity and coercive force of a material, can be determined. Retentivity, the material’s ability to retain a certain amount of residual magnetic field when the magnetizing force is removed after achieving saturation, depicts the value of
The heating pattern for CeGdZnFe [Gd,
The heating pattern of CeGdZn-ferrite [Gd,
It is a well-known fact that it is difficult to determine the Curie temperature (Tc) of a ferromagnetic body accurately [
The study showed the difference in the decayed ferromagnetism based on the difference of the magnetic material concerning the magnetic disordering process in the vicinity of Tc. Diminishing returns on temperature rise in CeGdZn-ferrite nanoparticles should occur near Tc. This causes a decrease in temperature for CeGdZn-ferrite nanoparticles as the starting temperature of tests increases towards Tc due to the ferromagnetic gradual loss of magnetization, given that losses and heat production are considered a result of hysteresis. Understanding ferromagnetic behavior above the body temperature will help to find if particles can heat to hyperthermia temperatures and self-limit near the Curie temperature. Cerium oxide nanoparticles with integrated gadolinium, exhibit combined therapeutic and diagnostic capabilities. This type of nanomaterial is highly promising for applications in the fields of biomedical imaging and magnetic hyperthermia.
The data used to support the findings of this study are available from the corresponding author upon request.
The author declares that there are no conflicts of interest regarding the publication of this paper.
The author would like to acknowledge the financial support for this work from the Deanship of Scientific Research (DSR), University of Tabuk, Saudi Arabia, under grant no. S-0163-1436.