Shape- and Cation-Engineered Ferrite Nanoparticles for Enhanced Theranostic Performance in Ovarian Cancer Tumor-Mimicking Phantom

Magnetic hyperthermia integrated with magnetic resonance imaging (MRI) requires nanoparticles that combine strong heating, T2 contrast, and hemocompatibility after systemic administration. Here, we prepared citrate-stabilized ferrite nanoparticles (Fe3O4, Co0.6Fe2.4O4, Zn0.3Fe2.7O4, and Zn0.35Mn0.25Fe2.4O4) in spherical (8-10.5 nm) and quasi-cubic (9-12.5 nm) forms, along with 35 nm Fe3O4 cubes. By coupling morphology engineering with spinel-lattice cation substitution, we tuned saturation magnetization, coercivity, T2-weighted signal attenuation, and heat dissipation in ovarian tumor-mimicking phantoms under clinically compatible alternating magnetic fields. The 35 nm Fe3O4 cube and quasi-cubic Zn0.35Mn0.25Fe2.4O4 generated the highest phantom temperature rises, whereas smaller spherical particles produced softer heating. All formulations were cytocompatible in SKOV3 cells, with >96% viability at 24 h. However, hemocompatibility distinguished the leading candidates: 35 nm Fe3O4 cubes induced red blood cell deformation despite minimal hemolysis, while 9 nm quasi-cubic Zn0.35Mn0.25Fe2.4O4 showed no change versus PBS up to 1,000 μg mL-1. Perfusable GelMA models under physiological flow further confirmed biocompatibility. MRI phantoms showed that Fe3O4 cubes produced extended signal voids that may obscure boundaries. Overall, 9.5 nm quasi-cubic Zn0.35Mn0.25Fe2.4O4 is the leading intravenous candidate, combining strong heating, T2 contrast, and hemocompatibility, whereas large Fe3O4 cubes are better suited for localized intratumoral hyperthermia.