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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]

• 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]