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This study investigates the distinctive characteristics of iron oxide magnetic nanoparticles (mNPs) and their potential application in cancer therapy, focusing on melanoma. Three types of mNPs, pre-validated for safety, underwent molecular analysis to uncover the activated signaling pathways in melanoma cells. Using the Western blot technique, the study revealed that mNPs induce cytotoxicity, hinder proliferation through ERK1/2 dephosphorylation, and prompt proapoptotic effects, including DNA damage by inducing H2AX phosphorylation. Additionally, in vitro magnetic hyperthermia notably enhanced cellular damage in melanoma cells. Moreover, the quantification of intracellular iron levels through Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis unveils the precise dosage required to induce cellular damage effectively. These compelling findings not only shed light on the therapeutic potential of mNPs in melanoma treatment but also open exciting avenues for future research, heralding a new era in the development of targeted and effective cancer therapies. Indeed, by discerning the effective dose, our approach becomes instrumental in optimizing the therapeutic utilization of iron oxide magnetic nanoparticles, enabling the induction of precisely targeted and controlled cellular responses. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) are considered as promising magnetic nanoheating agents for diagnostic as well as therapeutic applications due to their biocompatibility and tunability of magnetic properties. These nanoheating agents are commonly synthesized by coprecipitation of two iron precursors, though applying less amount of these chemicals may minimize the toxicity risks for biomedical purposes. The aim of this study is to address this issue by considering the high oxidation vulnerability of ferrous ions to ferric ions to synthesize SPIONs via a single-iron precursor under four varied oxidative conditions. The obtained results implied that the properties of SPIONs can be modified by the variation in the oxidizing conditions. Thereby, the optimal sample was produced as the oxygen/nitrogen flow ratio adjusted to 50% in the synthesis environment. The induction heating efficiency of this optimal sample was investigated under the exposure of varied alternating magnetic field (AMF), which resulted in a remarkable specific absorption rate (SAR) of 168.96 W g−1 while maintaining the temperature medium within the secure hyperthermia range. The cytotoxic effect of the optimal SPIONs sample against human liver carcinoma (HepG2) cells was determined using MTT assay, leading to a considerable decrement in the cell viability. The incorporation of SPIONs under the AMF exposure is, therefore, considered as an effectual mechanism to the tumor intervention. [ABSTRACT FROM AUTHOR]

The clinical translation of magnetic hyperthermia (MH) needs magnetic nanoparticles (MNPs) with enhanced heating properties and good biocompatibility. Many studies were devoted lately to the increase in the heating power of iron oxide MNPs by doping the magnetite structure with divalent cations. A series of MNPs with variable Zn/Fe molar ratios (between 1/10 and 1/1) were synthesized by using a high-temperature polyol method, and their physical properties were studied with different techniques (Transmission Electron Microscopy, X-ray diffraction, Fourier Transform Infrared Spectroscopy). At low Zn doping (Zn/Fe ratio 1/10), a significant increase in the saturation magnetization (90 e.m.u./g as compared to 83 e.m.u./g for their undoped counterparts) was obtained. The MNPs’ hyperthermia properties were assessed in alternating magnetic fields up to 65 kA/m at a frequency of 355 kHz, revealing specific absorption rates of up to 820 W/g. The Zn ferrite MNPs showed good biocompatibility against two cell lines (A549 cancer cell line and BJ normal cell line) with a drop of only 40% in the viability at the highest dose used (500 μg/cm2). Cellular uptake experiments revealed that the MNPs enter the cells in a dose-dependent manner with an almost 50% higher capacity of cancer cells to accommodate the MNPs. In vitro hyperthermia data performed on both cell lines indicate that the cancer cells are more sensitive to MH treatment with a 90% drop in viability after 30 min of MH treatment at 30 kA/m for a dose of 250 μg/cm2. Overall, our data indicate that Zn doping of iron oxide MNPs could be a reliable method to increase their hyperthermia efficiency in cancer cells.

In this paper we investigate the ability of zinc rich ferrite nanoparticles to induce hyperthermia on cancer cells using an alternating magnetic field (AMF). First, we synthesized ferrites and then we analyzed their physico-chemical properties by transmission electron microscopy, X-ray diffraction and magnetic and magnetocalorimetric measurements. We found that the polyol-made magnetically diluted particles are of 11 nm in size. They are superparamagnetic at body temperature (310 K) with a low but non-negligible magnetization. Interestingly, as nano-ferrimagnets they exhibit a Curie temperature of 366 K, close to the therapeutic temperature range. Their effect on human healthy endothelial (HUVEC) and malignant glioma (U87-MG) cells was also evaluated using MTT viability assays. Incubated with the two cell lines, at doses ≤100 µg mL −1 and contact times ≤4 h, they exhibit a mild in vitro toxicity. In these same operating biological conditions and coupled to AMF (700 kHz and 34.4 Oe) for 1 h, they rapidly induce a net temperature increase. In the case of tumor cells it reaches 4 K, making the produced particles particularly promising for self-regulated magnetically-induced heating in local glioma therapy. [ABSTRACT FROM AUTHOR]

The application of ferrite magnetic nanoparticles (MNPs) in medicine finds its rapidly developing emphasis on heating mediators for magnetic hyperthermia, the ever-promising “ fourth leg ” of cancer treatment. Usage of MNPs depends largely on the preparation processes to select optimal conditions and effective routes to finely tailor MNPs. Microwave heating, instead of conventional heating offers nanocrystals at significantly enhanced rate and yield. In this work, a facile mass-production microwave hydrothermal synthetic approach was used to synthesize stable ferromagnetic manganese and cobalt ferrite nanoparticles with sizes smaller than 14 nm from metal acetylacetonates in the presence of octadecylamine. Prolonging the reaction time from 15 to 60 min, led to ferrites with improved crystallinity while the sizes are slight increased. The high crystallinity magnetic nanoparticles showed exceptional magnetic heating parameters. In vitro application was performed using the human osteosarcoma cell line Saos-2 incubated with manganese ferrite nanoparticles. Hyperthermia applied in a two cycle process, while AC magnetic field remained on until the upper limit of 45 °C was achieved. The comparative results of the AC hyperthermia efficiency of ferrite nanoparticles in combination with the in vitro study coincide with the magnetic features and their tunability may be further exploited for AC magnetic hyperthermia driven applications. [ABSTRACT FROM AUTHOR]

The clinical translation of magnetic hyperthermia (MH) needs magnetic nanoparticles (MNPs) with enhanced heating properties and good biocompatibility. Many studies were devoted lately to the increase in the heating power of iron oxide MNPs by doping the magnetite structure with divalent cations. A series of MNPs with variable Zn/Fe molar ratios (between 1/10 and 1/1) were synthesized by using a high-temperature polyol method, and their physical properties were studied with different techniques (Transmission Electron Microscopy, X-ray diffraction, Fourier Transform Infrared Spectroscopy). At low Zn doping (Zn/Fe ratio 1/10), a significant increase in the saturation magnetization (90 e.m.u./g as compared to 83 e.m.u./g for their undoped counterparts) was obtained. The MNPs' hyperthermia properties were assessed in alternating magnetic fields up to 65 kA/m at a frequency of 355 kHz, revealing specific absorption rates of up to 820 W/g. The Zn ferrite MNPs showed good biocompatibility against two cell lines (A549 cancer cell line and BJ normal cell line) with a drop of only 40% in the viability at the highest dose used (500 μg/cm2). Cellular uptake experiments revealed that the MNPs enter the cells in a dose-dependent manner with an almost 50% higher capacity of cancer cells to accommodate the MNPs. In vitro hyperthermia data performed on both cell lines indicate that the cancer cells are more sensitive to MH treatment with a 90% drop in viability after 30 min of MH treatment at 30 kA/m for a dose of 250 μg/cm2. Overall, our data indicate that Zn doping of iron oxide MNPs could be a reliable method to increase their hyperthermia efficiency in cancer cells. [ABSTRACT FROM AUTHOR]

• SPIONs were synthesized using a sole Iron precursor. • Optimal CTAB surfactant quantity provided ad-micellar structure on SPIONs surface. • PCL biopolymer produced the core-shell SPIONs nanostructure. • PCL enhanced cytocompatibility and thermosensitive performance under AMF. • Coated SPIONs rendered a potent cytotoxicity on HepG2 under hyperthermia condition. Magnetic hyperthermia therapy of cancer is a promising alternative for the current chemotherapy and radiation options, due to its targeting capability and lower systemic toxicity. However, agglomeration vulnerability of the nano-heating agents in aqueous solutions, low control over the heat generation and dissipation at the target region, and eschewed clearance by the renal and reticuloendothelial systems remain as the main challenges for clinical translation of this approach. Here we report superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by using a single precursor, stabilized with a controlled micellar conformation, and coated with a thin polycaprolactone biopolymer shell to achieve enhanced cytocompatibility and thermosensitivity under external alternating magnetic field (AMF) of varied intensities. The in vitro investigations indicated a negligible influence of the polymer-coated SPIONs on cell viability of human liver cancer cells (HepG2) at a maximum concentration of 100 μg∙mL−1. However, the cell viability was reduced significantly to 40.1 ± 0.9% within the secure hyperthermia temperature range achieved by the heating effect of polymer-coated SPIONs in presence of AMF, depicting the on/off cytotoxicity phenomenon of polymer-coated SPIONs under AMF exposure. Therefore, the developed nanostructure presents a step-change as potential targeted nano-heating agents for new therapeutic options. [ABSTRACT FROM AUTHOR]