Doped Ferrite Nanoparticles Exhibiting Self-Regulating Temperature as Magnetic Fluid Hyperthermia Antitumoral Agents, with Diagnostic Capability in Magnetic Resonance Imaging and Magnetic Particle Imaging

Simple Summary Hyperthermia, a limited increase in tumor tissue temperature up to a maximum of 45 degrees C, has long been used in cancer treatment, either as a stand-alone therapy or in conjunction with chemo-/radiotherapy. Among the different physical procedures used, a particularly promising technique is magnetic fluid hyperthermia (MFH): this consists of the local administration of magnetic nanoparticles, followed by the application of alternating magnetic fields. One concern with this technique is the possibility of damage to healthy peritumoral tissue. The present study investigates innovative nanoparticles with self-regulating temperature, which should reduce this risk and thus mark a significant step forward in MFH. In an experimental model of aggressive breast cancer, we demonstrated a substantial reduction of tumor growth rate by using an experimental MFH protocol, transferable to clinical practice. These innovative nanomaterials present the added advantage of allowing non-invasive monitoring of temperature, by magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). This paper reports a comprehensive investigation of a magnetic nanoparticle (MNP), named M55, which belongs to a class of innovative doped ferrite nanomaterials, characterized by a self-limiting temperature. M55 is obtained from M48, an MNP previously described by our group, by implementing an additional purification step in the synthesis. M55, after citrate and glucose coating, is named G-M55. The present study aimed to demonstrate the properties of G-M55 as a diagnostic contrast agent for MRI and magnetic particle imaging (MPI), and as an antitumoral agent in magnetic fluid hyperthermia (MFH). Similar specific absorption rate values were obtained by standard MFH and by an MPI apparatus. This result is of interest in relation to the application of localized MFH by MPI apparatus. We demonstrated the biocompatibility of G-M55 in a triple-negative human breast cancer line (MDA-MB-231), and its efficacy as an MFH agent in the same cell line. We also demonstrated the efficacy of MFH treatment with G-M55 in an experimental model of breast cancer. Overall, our results pave the way for the clinical application of G-M55 as an MFH agent in breast cancer therapy, allowing not only efficient treatment by both standard MFH apparatus and MPI but also temperature monitoring.