Heating Rate and Ligand Ratio-Driven Morphological Evolution of Iron Oxide Nanoparticles and Their Impact on Magnetic Hyperthermia Performance

Iron oxide magnetic nanoparticles (IOMNPs) hold significant promise for magnetic hyperthermia (MH), a therapeutic modality for cancer treatment, yet their clinical efficacy is often limited by suboptimal heating performance. We present a simplified and highly reproducible thermal decomposition (TD) synthesis route that enables precise control over IOMNPs morphology and size by varying the heating rate (1.5–72 °C/min) and the oleic acid-to-iron acetylacetonate molar ratio (4:1–24:1). Unlike traditional TD methods that rely on complex setups or expensive ligands, our approach uses only three commercially available components (dibenzyl ether, oleic acid, and iron acetylacetonate) in a sealed, uniformly heated vessel, ensuring consistent heat transfer and reproducibility. The synthesized IOMNPs were characterized using TEM, XRD, and VSM, and their heating efficiency was evaluated through specific absorption rate (SAR) measurements in aqueous and solid environments. Our results revealed that heating rate and ligand ratio significantly influence IOMNPs morphology, with lower heating rates and higher ligand ratios favoring cubic shapes. Among the synthesized IOMNPs, near-cubic morphologies exhibited the highest SAR values, reaching up to 2150 W/g in aqueous media, among the highest reported for uncoated IOMNPs of comparable size. In vitro studies on A549 lung cancer cells demonstrated that near-cubic IOMNPs, despite their lower cellular uptake, achieved superior cancer cell death under an alternating magnetic field, with a 50% cell death temperature of 43.26 °C. This study advances the synthesis of shape-controlled IOMNPs, offering a reproducible synthesis route for optimizing MH performance.