7-nm Mn_0.5 Zn_0.5Fe₂O₄ superparamagnetic iron oxide nanoparticle (SPION): a high-performance theranostic for MRI and hyperthermia applications

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising contrast agents for imaging-guided cancer therapies. However, challenges such as the requirement for a high alternating magnetic field (AMF), dosage limitations, and suboptimal imaging contrast have hindered their practical applications. <b>Methods:</b> First, the optimal doping ratio of Mn and Zn in Mn_xZn_1-xFe₂O₄ nanoparticles synthesized using a modified high-temperature thermal decomposition method (mHTTD) was determined. Then, the magnetic and physical properties of the optimal 7-nm Mn_0.5Zn_0.5Fe₂O₄ SPIONs were systematically and comprehensively characterized via hysteresis measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray absorption fine structure (XAFS) spectroscopy, and X-ray absorption near edge structure (XANES) spectroscopy. Next, the stability, biosafety, biocompatibility, and theranostic performance of 7-nm Mn_0.5Zn_0.5Fe₂O₄ SPIONs in magnetic hyperthermia therapy (MHT) were evaluated by <i>in vivo</i> and <i>in vitro</i> studies involving mouse models, magnetic resonance imaging (MRI), and bioassays. The results were then compared with those for conventional SPIONs. <b>Results:</b> Under an AMF of 140 Oe at 100 kHz, 7-nm Mn_0.5Zn_0.5Fe₂O₄ SPIONs demonstrated significantly higher heat production than conventional SPIONs. Following surface modification with methoxy-PEG-silane, PEGylated 7-nm Mn_0.5Zn_0.5Fe₂O₄ SPIONs showed excellent monodispersity and magnetic properties, with an exceptionally high T2 relaxivity (r2). <b>Conclusions:</b> The high <i>in vitro</i> and <i>in vivo</i> theranostic performance of PEGylated 7-nm Mn_0.5Zn_0.5Fe₂O₄ SPIONs as efficient and stable contrast agents for treating glioblastoma, encompassing strengthened magnetic hyperthermia, activated anti-tumor immunity, and remarkable T2 contrast enhancement, underscores the potential of precisely designed ferrites to concurrently enhance the T2 contrast and magnetocaloric properties for optimal theranostic outcomes. Our study provides a compelling rationale for the development of tailored magnetic nanoprobes for improved glioblastoma theranostics.