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.