Tailored nanoparticles for magnetic hyperthermia: Highly stable aqueous dispersion of Mn-substituted magnetite superparamagnetic nanoparticles by double surfactant coating for improved heating efficiency

This study presents a significant advancement in cancer therapy through the application of Mn-substituted magnetite superparamagnetic (SPM) nanoparticles, highlighting the potential of magnetic fluid hyperthermia (MFH) as an effective modality. However, its clinical applications have been limited by challenges such as low heating performance, agglomeration of magnetic nanoparticles (MNPs) in blood veins, and cytotoxicity. To address these crucial issues, surface engineered MNPs were synthesised by adopting a reverse micelles-based co-precipitation approach that effectively overcomes MNP agglomeration, ensuring uniform dispersion of the nanoparticles. Through careful optimization of Mn ion substitution within magnetite, we have achieved a significant enhancement in the heating performance of the magnetite SPM nanoparticles. The substitution of Mn2+ ions in magnetite has notably increased the specific absorption rate (SAR) value, as evidenced by a remarkable 181% increase (SAR: 510 kW/kg) obtained using the Box Lucas Method. This enhancement can be attributed to the elevated saturation magnetization resulting from the appropriate cation distribution within the MNPs. Furthermore, the increase in spin relaxation time with higher Mn concentration also contributes to the improvement in SAR values as MNPs retain their magnetic moments for an extended period before relaxing, leading to enhanced energy dissipation and higher SAR values. The hemolysis assays demonstrated minimal hemolysis rates (<5%) when exposed to red blood cells (RBCs), confirming the high biocompatibility of the MNPs. Additionally, MTT assays revealed excellent cytocompatibility (>90% cell viability) for Human Embryonic Kidney (HEK-293) cells across all compositions, further affirming the potential of these MNPs for clinical treatments. Overall, this study unveils a sustainable approach for cancer therapy using Mn-substituted magnetite SPM nanoparticles. Their remarkable heating performance and excellent biocompatibility make them promising for clinical applications in MFH.