Core Size and PEG Coating Govern the Dual Magnetic Particle Imaging and Hyperthermia Performance of Iron Oxide Nanoparticles

Magnetic particle imaging (MPI) and magnetic hyperthermia therapy (MHT) both rely strongly on the dynamic magnetic response of magnetic nanoparticles (MNPs), yet the particle design requirements for achieving strong imaging contrast and efficient heating are not always aligned. Here, we systematically investigate the effects of core size and PEG surface coating on the dual MPI-MHT performance of iron oxide MNPs. Six formulations with core sizes of 10, 20, and 30 nm, either uncoated Fe3O4 or PEG-coated Fe3O4 (Fe3O4@PEG), were systematically evaluated. MPI performance was assessed using magnetic particle spectroscopy (MPS) under an excitation field of 10 mT at 7.7 and 11.4 kHz. Harmonic analysis revealed that 20 nm Fe3O4@PEG nanoparticles generated the strongest MPI response, characterized by enhanced higher-order harmonic magnitudes and slower harmonic decay. MHT performance was then evaluated under various alternating magnetic field (AMF) conditions: 30 mT at 101.5 kHz, 15 mT at 434.4 kHz, 25 mT at 252.5 kHz, and 10 mT at 951.8 kHz. Results demonstrate that 20 nm Fe3O4@PEG nanoparticles also showed superior heating efficiency, especially under low-field, high-frequency excitation. These findings suggest that a 20 nm core size, combined with a PEG coating, provides an optimal balance between rapid magnetic response, colloidal stability, and energy dissipation. Furthermore, colloidal stability over seven days and cell viability assays confirm that the MNPs are colloidally stable and that 20 and 30 nm MNPs are biocompatible under the tested conditions for up to 48 h. This study provides a rational design framework for developing dual-functional iron oxide nanoparticles for image-guided magnetic hyperthermia and other integrated diagnostic-therapeutic biomedical applications.