Abstract
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. Methods: First, the optimal doping ratio of Mn and Zn in MnxZn1-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 Mn0.5Zn0.5Fe2O4 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 Mn0.5Zn0.5Fe2O4 SPIONs in magnetic hyperthermia therapy (MHT) were evaluated by in vivo and in vitro studies involving mouse models, magnetic resonance imaging (MRI), and bioassays. The results were then compared with those for conventional SPIONs. Results: Under an AMF of 140 Oe at 100 kHz, 7-nm Mn0.5Zn0.5Fe2O4 SPIONs demonstrated significantly higher heat production than conventional SPIONs. Following surface modification with methoxy-PEG-silane, PEGylated 7-nm Mn0.5Zn0.5Fe2O4 SPIONs showed excellent monodispersity and magnetic properties, with an exceptionally high T2 relaxivity (r2). Conclusions: The high in vitro and in vivo theranostic performance of PEGylated 7-nm Mn0.5Zn0.5Fe2O4 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.