Nanotheranostics 2021; 5(3):333-347. doi:10.7150/ntno.55695

Research Paper

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

Marco Gerosa1*, Marco Dal Grande2*, Alice Busato3,4*, Federica Vurro3, Barbara Cisterna4, Enrico Forlin5, Filippo Gherlinzoni6, Giovanni Morana6, Michele Gottardi6, Paolo Matteazzi5,6, Adolfo Speghini2, Pasquina Marzola3✉

1. Department of Diagnostics and Public Health, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy.
2. Nanomaterials Research Group, Department of Biotechnology, University of Verona and INSTM, RU Verona, Strada Le Grazie 15, I-37134 Verona, Italy.
3. Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy.
4. Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
5. MBN Nanomaterialia S.p.A., Via Giacomo Bortolan, 42, 31050 Carbonera Treviso, Italy.
6. Foundation for Nanotheranostics Research in Cancer Therapy, RNC, Treviso, Italy.
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Gerosa M, Grande MD, Busato A, Vurro F, Cisterna B, Forlin E, Gherlinzoni F, Morana G, Gottardi M, Matteazzi P, Speghini A, Marzola P. Nanoparticles exhibiting self-regulating temperature as innovative agents for Magnetic Fluid Hyperthermia. Nanotheranostics 2021; 5(3):333-347. doi:10.7150/ntno.55695. Available from

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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 r2 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 T2 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.

Keywords: Magnetic Fluid Hyperthermia, Self-regulating temperature, Curie temperature, Nanoparticles, MRI.