Correlation between effects of the particle size and magnetic field strength on the magnetic hyperthermia efficiency of dextran-coated magnetite nanoparticles.

A precise control of the particle size of dextran-coated magnetite nanoparticles (Dex-M NPs) was successfully performed by combination of co-precipitation and hydrothermal synthesis methods. The Dex-M NPs, in the size range 3.1-18.9 nm, were used to fabricate biocompatible magnetic fluids for application in magnetic hyperthermia therapy (MHT). The effects of the carrier fluid viscosity, particle size, and applied magnetic field strength (Happl) on the specific loss power (SLP) of the Dex-M NPs were investigated at a fixed magnetic field frequency (f). The experimental results show that SLP of the larger Dex-M NPs significantly decreases for a highly viscous carrier fluid. Moreover, regardless of the carrier fluid viscosity, the particle size strongly affects the heating efficiency of the Dex-M NPs. SLP ranges from zero for the smallest Dex-M NPs (with particle size d = 3.1 nm) to 55.21 W/g for the largest ones (d = 18.9 nm) at Happl = 28 kA/m and f = 120 kHz. The most important finding in our research is that, at a fixed frequency, the optimal size of the Dex-M NPs (the size that maximizes SLP) shows a rising trend by enhancing Happl. In fact, the highest values of SLP at Happl = 11 kA/m, 13 - 17.5 kA/m, and 19 - 28 kA/m are obtained for the Dex-M NPs with d = 11.5 nm, 15 nm, and 18.9 nm, respectively. The shift of optimal size to the higher values by increasing Happl could shed light on the correlated effects of the particle size and Happl on the heating efficiency of magnetic nanoparticles (MNPs) and pave a new way toward the better tuning of them for an effective and biologically safe treatment.

One-pot preparation of hyaluronic acid-coated iron oxide nanoparticles for magnetic hyperthermia therapy and targeting CD44-overexpressing cancer cells.

In the present study, a facile one-pot hydrothermal method is introduced for preparation of hyaluronic acid-coated Fe3O4 nanoparticles (Fe3O4@HA NPs) for theranostic applications. In the proposed method, hyaluronic acid acts simultaneously as a biocompatible coating layer and as a targeting ligand for CD44 receptor overexpressed on the surface of breast cancer cells. The obtained product with narrow hydrodynamic size distribution exhibited a high colloidal stability at physiological pH for more than three months. Cytotoxicity measurements indicated a negligible toxicity of the prepared sample against L929 normal cells. Preferential targeting of Fe3O4@HA NPs to CD44-overexpressing cancer cells was studied by comparing the uptake of the prepared nanoparticles by MDA-MB-231 cancer cells (positive CD44 expression) and L929 normal cells (negative CD44 expression). Uptake of the Fe3O4@HA NPs by MDA-MB-231 cells was found to be 4-fold higher than the normal cells. Also, the in vitro analysis showed that, the uptake of Fe3O4@HA NPs by MDA-MB-231 breast cancer cells is significantly enhanced as compared to non-targeted dextran-coated Fe3O4 NPs. Moreover, the heat generation capability of the Fe3O4@HA NPs for magnetic hyperthermia application was studied by exposing the prepared nanoparticles to different safe alternating magnetic fields (f = 120 kHz, H = 8, 10, and 12 kA/m). The intrinsic loss power obtained for Fe3O4@HA NPs was about 3.5 nHm2/kg, which is about 25-fold larger than that of obtained for commercial available Fe3O4 nanoparticles for biomedical applications. Good colloidal stability, biocompatibility, high heating efficacy, and targeting specificity to CD44 receptor-overexpressing cancer cells could make the Fe3O4@HA NPs as a promising multifunctional platform for diagnosis and therapeutic applications.

Effects of multiple injections on the efficacy and cytotoxicity of folate-targeted magnetite nanoparticles as theranostic agents for MRI detection and magnetic hyperthermia therapy of tumor cells.

Folate-targeted iron oxide nanoparticles (FA@Fe3O4 NPs) were prepared by a one-pot hydrothermal method and then used as cancer theranostic agents by combining magnetic resonance imaging (MRI) and magnetic hyperthermia therapy (MHT). Crystal structure, morphology, magnetic properties, surface functional group, and heating efficacy of the synthesized nanoparticles were characterized by XRD, TEM, VSM, FTIR, and hyperthermia analyses. The results indicated that the crystal structure, magnetic properties, and heating efficacy of the magnetite nanoparticles were improved by hydrothermal treatment. Toxicity of the prepared NPs was assessed in vitro and in vivo on the mammary cells and BALB/c mice, respectively. The results of the in vitro toxicity analysis showed that the FA@Fe3O4 NPs are relatively safe even at high concentrations of the NPs up to 1000 µg mL-1. Also, the targetability of the FA@Fe3O4 NPs for the detection of folate over-expressed cancer cells was evaluated in an animal model of breast tumor using MRI analysis. It was observed that T2-weighted magnetic resonance signal intensity was decreased with the three-time injection of the FA@Fe3O4 NPs with 24 h interval at a safe dose (50 mg kg-1), indicating the accumulation and retention of the NPs within the tumor tissues. Moreover, the therapeutic efficacy of the MHT using the FA@Fe3O4 NPs was evaluated in vivo in breast tumor-bearing mice. Hyperthermia treatment was carried out under a safe alternating magnetic field permissible for magnetic hyperthermia treatment (f = 150 kHz, H = 12.5 mT). The therapeutic effects of the MHT were evaluated by monitoring the tumor volume during the treatment period. The results showed that the mice in the control group experienced an almost 3.5-fold increase in the tumor volume during 15 days, while, the mice in the MHT group had a mild increase in the tumor volume (1.8-fold) within the same period (P < 0.05). These outcomes give promise that FA@Fe3O4 NPs can be used as theranostic agents for the MRI and MHT applications.

Physics responsible for heating efficiency and self-controlled temperature rise of magnetic nanoparticles in magnetic hyperthermia therapy.

Magnetic nanoparticles as heat-generating nanosources in hyperthermia treatment are still faced with many drawbacks for achieving sufficient clinical potential. In this context, increase in heating ability of magnetic nanoparticles in a biologically safe alternating magnetic field and also approach to a precise control on temperature rise are two challenging subjects so that a significant part of researchers' efforts has been devoted to them. Since a deep understanding of Physics concepts of heat generation by magnetic nanoparticles is essential to develop hyperthermia as a cancer treatment with non-adverse side effects, this review focuses on different mechanisms responsible for heat dissipation in a radio frequency magnetic field. Moreover, particular attention is given to ferrite-based nanoparticles because of their suitability in radio frequency magnetic fields. Also, the key role of Curie temperature in suppressing undesired temperature rise is highlighted.

High impact of in situ dextran coating on biocompatibility, stability and magnetic properties of iron oxide nanoparticles.

Biocompatible ferrofluids based on dextran coated iron oxide nanoparticles were fabricated by conventional co-precipitation method. The experimental results show that the presence of dextran in reaction medium not only causes to the appearance of superparamagnetic behavior but also results in significant suppression in saturation magnetization of dextran coated samples. These results can be attributed to size reduction originated from the role of dextran as a surfactant. Moreover, weight ratio of dextran to magnetic nanoparticles has a remarkable influence on size and magnetic properties of nanoparticles, so that the sample prepared with a higher weight ratio of dextran to nanoparticles has the smaller size and saturation magnetization compare with the other samples. In addition, the ferrofluids containing such nanoparticles have an excellent stability at physiological pH for several months. Furthermore, the biocompatibility studies reveal that surface modification of nanoparticles by dextran dramatically decreases the cytotoxicity of bare nanoparticles and consequently improves their potential application for diagnostic and therapeutic purposes.