Wet Ball Milling Synthesis of Iron Oxide Nanoparticles for High-Efficiency, Controllable Magnetic Hyperthermia in Ovarian Cancer.

Magnetic nanoparticles (MNPs) are attracting increasing attention for applications in energy, environment, and biomedicine. Among all MNP synthesis methods, ball milling is a cost-effective route for producing large quantities of MNPs at low cost. This work aims to investigate the magnetic hyperthermia performance of MNPs synthesized through a mechanochemical ball milling approach. Herein, we first varied the milling conditions and thoroughly characterized the physical properties of the produced MNPs; later, their hyperthermia performance was studied under different alternating magnetic fields (AMF). We report that the MNPs, after ball milling for up to 55 h at 200 rpm, show a higher magnetite phase with an average hydrodynamic size of ~270 nm and irregular morphology. These MNPs were subjected to clinically safe AMF (30 mT, 101.5 kHz), yielding a maximum temperature rise of ~50 °C, including in the SKOV3 cancer cell medium. Additionally, to enable controlled heating and avoid unintended damage to healthy tissues, we applied pulsed AMFs, achieving a temperature of ~30 °C. Lastly, the cellular uptake, colloidal stability, and biocompatibility tests were conducted on suspensions. This study reports a straightforward, cost-effective, large-scale synthesis route for MNPs and highlights their effective hyperthermia performance, showcasing their potential for future safer tumor treatment.