Nanoparticles exhibiting self-regulating temperature as innovative agents for Magnetic Fluid Hyperthermia

Abstract

During the last few years, for therapeutic purposes in oncology, considerable attention has been focused on a method called magnetic fluid hyperthermia (MFH) based on local heating of tumor cells. In this paper, an innovative, promising nanomaterial, M48 composed of iron oxide-based phases has been tested. M48 shows self-regulating temperature due to the observable second order magnetic phase transition from ferromagnetic to paramagnetic state. A specific hydrophilic coating based on both citrate ions and glucose molecules allows high biocompatibility of the nanomaterial in biological matrices and its use in vivo . MFH mediator efficiency is demonstrated in vitro and in vivo in breast cancer cells and tumors, confirming excellent features for biomedical application. The temperature increase, up to the Curie temperature, gives rise to a phase transition from ferromagnetic to paramagnetic state, promoting a shortage of the r 2 transversal relaxivity that allows a switch in the contrast in Magnetic Resonance Imaging (MRI). Combining this feature with a competitive high transversal (spin-spin) relaxivity, M48 paves the way for a new class of temperature sensitive T 2 relaxing contrast agents. Overall, the results obtained in this study prepare for a more affordable and tunable heating mechanism preventing the damages of the surrounding healthy tissues and, at the same time, allowing monitoring of the temperature reached.

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

“…Centrifugation was used to extract nanosized particles (<200 nm). This process further improves the one previously used [ 6 ]: detailed processing parameters are provided courtesy of MBN Nanomaterialia S.p.A.…”

“…The challenges of MFH are the need to deliver a large quantity of MNPs to the tumor tissue, and the risk of overheating healthy peritumoral tissue [ 6 ]. In currently applied preclinical and clinical protocols, nanoparticles are injected directly into the tumor tissue.…”

“…The risk of overheating healthy peritumoral tissue has been previously addressed by us and by other groups [ 6 , 8 ] using self-regulating temperature MNPs [ 9 ]. Gerosa et al report an extensive investigation of a self-regulating temperature nanomaterial, synthesized by MBN Nanomaterialia S.p.A. (Treviso, Italy).…”

“…Above the T C , magnetization is negligible and the heating effect of the AMF ceases. Interestingly, above Tc, a sharp decrease in transverse MRI relaxivity occurs, meaning that the MNP is suitable for use as a temperature-sensitive contrast agent [ 6 ]. In principle, these properties are particularly useful when the nanomaterial is integrated into biological matrices, making it possible to limit the maximum temperature and, at the same time, monitor temperature changes by means of imaging.…”

“…M55, the MNP studied in the present paper, is obtained from previously described M48 material [ 6 ], by implementing an additional purification step in the synthesis process so as to remove potential paramagnetic by-products from the liquid suspension. In investigating this class of materials, we have already considered their properties as theranostic agents for MPI, in view of the foreseen application of MPI in MFH [ 4 , 7 ].…”