Research progress on magnetic nanoparticles for magnetic induction hyperthermia of malignant tumor

As a new malignant tumor therapy method with low side effect, high safety and efficiency, magnetic induction hyperthermia (MIH) has attracted great attention in recent years. As magnetic induction heating media, magnetic nanoparticles (MNPs) are critical for the development of MIH. For clinical safety, the MNPs need a high heating efficiency to reduce the applied dose, minimizing the risk of side effect. Increasing the saturation magnetization and initial susceptibility, adjusting the magnetocrystalline anisotropy constant and particle size to the optimal values are the effective methods of improving heating efficiency. On the other hand, a suitable Curie temperature is desired to realize the self-regulation of the therapy temperature, avoiding the use of clumsy and expensive temperature monitoring and control devices. Substituting the magnetic ions in tetrahedral (A) site of the spinel ferrite with nonmagnetic ions or magnetic ions with smaller magnetic moments can effectively reduce the superexchange interaction between the A and B (octahedral) sites, decreasing Curie temperature. Yet, the reduction of the Curie temperature by ion doping usually reduces the saturation magnetization, decreasing heating efficiency. Increasing the fraction of heat generated by relaxation loss and increasing the saturation magnetization may be used to improve the heating efficiency.     

Tailoring the hyperthermia potential of magnetite nanoparticles via gadolinium ION substitution

Magnetic nanoparticles are one of the most promising candidates to achieve localization of heat in the region of cancerous tissue. Modified co-precipitation technique is carried out to synthesize Gd_xFe_3-xO₄ (where, x = 0.00 (IO), 0.04 (IOG02), 0.08 (IOG04), 0.12 (IOG06), 0.16 (IOG08), 0.20 (IOG10). A systematic characterization was performed to study the structural, morphological, elemental, and magnetic properties of the synthesized nanoparticles using X-Ray diffraction (XRD), Field emission scanning microscopy (FESEM), Energy Dispersive Spectroscopy (EDS), Vibrating sample magnetometer (VSM) respectively. The structural analysis revealed the single-phase crystalline nature of magnetite, with the co-existence of secondary phase hematite and goethite beyond x ≥ 0.16. The morphological analysis implied an increase in particle size due to Gd substitution with particle sizes ranging from 7 to 19 nm. Magnetic measurements revealed a magnetic transformation from superparamagnetic nature with magnetic coercivity and remanence to weak ferromagnetic nature upon an increase in the gadolinium content of magnetite. Further, hyperthermia studies showed that with increasing gadolinium concentration, the heating rate, specific absorption rate, and the intrinsic loss power of gadolinium substituted magnetites were increased. The increased specific absorption rate of gadolinium substituted magnetites with low HF factors makes them ideal for clinical hyperthermia applications.     

Preparation,physicochemical characterization,and AC induction heating properties of colloidal aggregates of ferrimagnetic cobalt ferrite nanoparticles coated with a bio-compatible polymer

AC induction heating properties of colloidal nano-aggregates of ferrimagnetic cobalt ferrite magnetic nanoparticles (MNPs) are reported in this study. Bio-compatible chitosan polymer-coated CoFe₂O₄ MNPs are synthesized using a co-precipitation method. Powder X-ray diffraction indicates the formation of mixed spinel structures for the uncoated (CP) and chitosan-coated (CP–CHN) MNPs, which is also supported by the cation distributions obtained from the Mössbauer spectra. The presence of chitosan coating on the surface of the CP-CHN MNPs is confirmed using X-ray photoelectron and Fourier transform infrared spectroscopy studies. Transmission electron microscopy shows primary particle sizes of ∼13 nm, which is larger than the superparamagnetic size limit of the CoFe₂O₄ MNPs. Hence, the CP and CP-CHN MNPs exhibit ferrimagnetic behaviour at room temperature with estimated saturation magnetization values of ∼77.4 emu/g and ∼74.4 emu/g, respectively. The average hydrodynamic diameter is found to be ∼90 ± 8 nm for an aqueous dispersion of the CP-CHN MNPs, which indicate the formation of colloidal nano-aggregates due to the ferrimagnetic interaction of the primary MNPs. The CP-CHN sample exhibits a significantly high AC induction heating efficiency of ∼267.2 ± 4.0 W/g_Fe, where the higher heating efficiency is attributed to the combination of hysteresis and relaxation-mediated magneto-thermal energy conversion, as confirmed using Stoner-Wohlfarth model-based dynamic hysteresis loop calculations. Further, the heating efficiency decreases with increasing sample concentration due to an increase in dipolar interaction, which is confirmed using semi-empirical calculations, where a lowering of the initial susceptibility is observed at higher concentrations. The higher AC induction heating efficiency, coupled with the demonstrated significant bio-compatibility during in vitro cytotoxicity studies, make the cobalt ferrite nano-aggregates potential candidates for magnetic hyperthermia.     

Synthesis and magneto-structural properties of chitosan coated ultrafine cobalt ferrite nanoparticles for magnetic fluid hyperthermia in viscous medium

AC induction heating mediated magnetic fluid hyperthermia of superparamagnetic nanoparticles (MNPs) is being widely explored for localized thermo-therapy of tumours. One of the primary hindrances for rapid adaptation of this technique is the loss of heating efficiency when the MNPs are placed within the viscous tissue medium, which necessitates undesired increase in MNP concentrations or exposure time during practical applications. With an objective to mitigate this, here we report the viscosity independent magnetic hyperthermia properties of biocompatible ultrafine (average size ～ 2.5 nm) chitosan-coated superparamagnetic CoFe₂O₄ MNPs synthesized using a low-cost co-precipitation technique. The presence of the chitosan coating is confirmed from Fourier transform infrared and X-ray photoelectron spectroscopy. The superparamagnetic nature of the synthesized MNPs at 300 K is confirmed from Mössbauer spectroscopy, isothermal and temperature dependent magnetization studies. Experimental findings indicate a higher field-induced heating efficiency for the chitosan-coated MNPs due to superior colloidal stability. The ultrafine size, combined with higher anisotropy energy density, results in viscosity independent Nèel relaxation-dominated magneto-thermal energy conversion for the CoFe₂O₄ MNPs. Experimental results reveal negligible loss of heating efficiency due to partial abrogation of Brownian relaxation when the chitosan-coated MNPs are immobilized in a tissue-equivalent agar medium, which is beneficial for practical applications. The heating efficiency of ～72.1 ± 2.8 W/g_Fe (at 33.1 kA/m and 126 kHz), obtained in the present study for the chitosan-coated MNPs, is higher than the previously documented values for ultrafine CoFe₂O₄ MNPs, which is useful for reducing the exposure time during practical applications. Further, the chitosan coating rendered the ultrafine CoFe₂O₄ MNPs bio-compatible against L929 cell line. The satisfactory magnetic fluid hyperthermia efficiency, negligible room temperature coercivity, retention of the field-induced heating efficiency in tissue-equivalent agar medium due to Nèel-dominated relaxation dynamics and superior biocompatibility, make the chitosan-coated ultrafine CoFe₂O₄ MNPs an attractive candidate for practical MFH applications.     

Green facile synthesis of low-toxic superparamagnetic iron oxide nanoparticles (SPIONs) and their cytotoxicity effects toward Neuro2A and HUVEC cell lines

Superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) were synthesized by co-precipitation using polyvinyl alcohol (PVA) as a capping agent under alkaline condition. The produced X-ray diffraction (XRD) pattern evidenced the presence of peaks corresponding to the inverse spinel structure of the prepared SPIONs. Debye-Scherrer and field emission scanning microscopy (FESEM) showed the prepared SPIONs to be well-defined with about <?50?nm size. Likewise, the superparamagnetic properties of the SPIONs measured by Vibrating Sample Magnetometer (VSM) showed high saturation magnetization (~ 65.36?emu/g). The in vitro cytotoxicity studies on Neuro2A and HUVEC cells have mentioned low toxic and non-toxic SPIONs, respectively in a range of concentrations (1.17–150?μg/ml), thus, we reckon that the synthesized SPIONs will have persistent utilization in different fields of medical applications.     

Synthesis and characterization of Sr2+ and Gd3+ doped magnetite nanoparticles for magnetic hyperthermia and drug delivery application

Commendable efforts have been gingered towards the fight against cancer. Nevertheless, it remains a major public health concern due to its predominant cause of death globally. Given this, we synthesized two different nanoparticles, Sr²⁺ and Gd³⁺ doped magnetite for magnetic hyperthermia and drug delivery application. Based on the characterization, the diffractogram shows that only one phase related to magnetite with a crystallite size of 10 nm was formed. TEM images revealed nanoparticles of spherical shapes of approximately 12 nm. There is no difference in magnetic saturation of the as-received synthesized samples (Fe₃O₄@Sr and Fe₃O₄@Gd), while the BET-specific surface area of Fe₃O₄@Gd is 8 m² g⁻¹ higher than Fe₃O₄@Sr. The heat generation in alternating magnetic field (the magnetic hyperthermia) of Fe₃O₄@Sr functionalized with citric acid and loaded with 5- fluorouracil (Fe₃O₄@Sr@CA@5-flu) is slower than Fe₃O₄@Gd@CA@5-flu. The specific absorption rate (SAR) of Fe₃O₄@Gd@CA@5-flu, 112.0 ± 10.4 W g⁻¹ was found to be higher than that of Fe₃O₄@Sr@CA@5-flu. The thermogram shows that 11% of the drug was successfully loaded on Fe₃O₄@Gd@CA@5-flu. The release of the antitumor drug by the synthesized nanoparticle drug carriers for ovarian cancer (SKOV-3 cells) therapy showed that more than 50% of the cancer cell’s viability was reduced after 72 h of incubation. The synthesized nanoparticles demonstrated a promising drug carrier for the treatment of SKOV-3 cells.     

The heating effect of iron-cobalt magnetic nanofluids in an alternating magnetic field: application in magnetic hyperthermia treatment

In this research, FeCo alloy magnetic nanofluids were prepared by reducing iron(III) chloride hexahydrate and cobalt(II) sulfate heptahydrate with sodium borohydride in a water/CTAB/hexanol reverse micelle system for application in magnetic hyperthermia treatment. X-ray diffraction, electron microscopy, selected area electron diffraction, and energy-dispersive analysis indicate the formation of bcc-structured iron-cobalt alloy. Magnetic property assessment of nanoparticles reveals that some samples are single-domain superparamagnetic, while others are single- or multi-domain ferromagnetic. The stability of the magnetic fluids was achieved by using a CTAB/1-butanol surfactant bilayer. Results of Gouy magnetic susceptibility balance experiments indicate good stability of FeCo nanoparticles even after dilution. The inductive properties of corresponding magnetic fluids including temperature rise and specific absorption rate were determined. Results show that with increasing of the nanoparticle size in the single-domain size regime, the generated heat increases, indicating the significant effect of the hysteresis loss. Finally, the central parameter controlling the specific absorption rate of nanoparticles was introduced, the experimental results were compared with those of the Stoner-Wohlfarth model and linear response theory, and the best sample for magnetic hyperthermia treatment was specified.     

Structural properties of magnetic nanoparticles determine their heating behavior - an estimation of the in vivo heating potential

Magnetically induced heating of magnetic nanoparticles (MNP) in an alternating magnetic field (AMF) is a promising minimally invasive tool for localized tumor treatment by sensitizing or killing tumor cells with the help of thermal stress. Therefore, the selection of MNP exhibiting a sufficient heating capacity (specific absorption rate, SAR) to achieve satisfactory temperatures in vivo is necessary. Up to now, the SAR of MNP is mainly determined using ferrofluidic suspensions and may distinctly differ from the SAR in vivo due to immobilization of MNP in tissues and cells. The aim of our investigations was to study the correlation between the SAR and the degree of MNP immobilization in dependence of their physicochemical features.In this study, the included MNP exhibited varying physicochemical properties and were either made up of single cores or multicores. Whereas the single core MNP exhibited a core size of approximately 15 nm, the multicore MNP consisted of multiple smaller single cores (5 to 15 nm) with 65 to 175 nm diameter in total. Furthermore, different MNP coatings, including dimercaptosuccinic acid (DMSA), polyacrylic acid (PAA), polyethylenglycol (PEG), and starch, wereinvestigated. SAR values were determined after the suspension of MNP in water. MNP immobilization in tissues was simulated with 1% agarose gels and 10% polyvinyl alcohol (PVA) hydrogels.The highest SAR values were observed in ferrofluidic suspensions, whereas a strong reduction of the SAR after the immobilization of MNP with PVA was found. Generally, PVA embedment led to a higher immobilization of MNP compared to immobilization in agarose gels. The investigated single core MNP exhibited higher SAR values than the multicore MNP of the same core size within the used magnetic field parameters. Multicore MNP manufactured via different synthesis routes (fluidMAG-D, fluidMAG/12-D) showed different SAR although they exhibited comparable core and hydrodynamic sizes. Additionally, no correlation between ζ-potential and SAR values after immobilization was observed.Our data show that immobilization of MNP, independent of their physicochemical properties, can distinctly affect their SAR. Similar processes are supposed to take place in vivo, particularly when MNP are immobilized in cells and tissues. This aspect should be adequately considered when determining the SAR of MNP for magnetic hyperthermia.     

Preparation of Janus-type superparamagnetic iron oxide nanoparticles modified with functionalized PCL/PHEMA via photopolymerization for dual drug delivery

In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by the coprecipitation of FeCl₂˙4H₂O and FeCl₃˙6H₂O and applied as a core for preparation of Janus nanoparticles. Accordingly, freshly modified methacrylated iron oxide nanoparticles were reacted with two functionalized polymers. Acrylated poly(ε-caprolactone) (PCL) and acrylated poly(2-hydroxyethyl methacrylate) (PHEMA) were synthesized via ring-opening and free-radical polymerization, respectively, and subsequent modification with acryloyl chloride. Acrylated PCL as the hydrophobic part and acrylated PHEMA as the hydrophilic domain were grafted on the surface of methacrylated iron oxide nanoparticles with two morphologies. Pickering emulsion and solution photopolymerization reactions were used to prepare nanoparticles with “Janus” and “mixed” morphologies, respectively. The products were characterized in each step using Fourier-transform infrared spectroscopy (FT-IR), Proton nuclear magnetic resonance (¹H-NMR), thermogravimetric analysis (TGA), dynamic light scaterring (DLS), transmission electron microscope (TEM), vibrating-sample magnetometer (VSM), energy dispersive X-ray (EDX), and ultraviolet–visible spectroscopy (UV-Vis). Quercetin and 5-FU (as two anticancer drugs) were loaded in the mentioned nanoparticles, and the drug loading capacity and encapsulation efficiency (EE) of these nanoparticles were calculated. in vitro release behavior at two pH values (5.8 and 7.4) and at 37°C demonstrated that morphology can affect the release profile. Finally, rat C6 cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay for drug-free and drug-loaded nanoparticles.     

Green synthesis of novel lanthanum doped copper oxide nanoparticles for photocatalytic application: Correlation between experiment and COMSOL simulation

Treatment of waste water via photocatalysis is one of the most effective, economical and environment friendly process. In this study, green method (leaf extract of Citrus Medica Linn.) is used to synthesize pure and lanthanum (La)-(1,2 & 3 wt%) doped copper oxide nanoparticles (CuO-NPs). Different characterization techniques such as XRD, SEM, EDS, UV/VIS, PL and FTIR are utilized to investigate their physical, chemical, optical and structural properties. The synthesized material is used as photocatalyst for degradation of methylene blue (MB) dye. Interestingly, the La doped CuO-NPs have exhibited unique results. Variation in dopant concentration reduces the particle size (40.82 ± 0.04 nm to 31.89 ± 0.02 nm) and band gap of material shifts towards visible region (3.03 eV–2.71 eV). During photocatalysis, doping reduces the electron-hole pair recombination rate which makes it a potential photocatalyst. Maximum degradation efficiency of 84% is observed in 150 min for 2% La doped CuO-NPs which reveals that 2% La doping is optimal. Further increase in dopant concentration increases band gap, therefore, degradation efficiency drops to 75%. Simulation of this work is carried out using COMSOL Multiphysics 5.3a Licensed version. A 2D model is constructed and CuO-NPs is considered as photocatalyst in order to correlate simulated and experimental photocatalytic degradation of MB and rhodamine B (RhB) dye. Comparative analysis of rate constants revealed that the trend given by simulation is very close to the experimental observations.