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Débora Bonvin

Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland

 Lately, magnetic nanoparticles have been the focus of intense research, especially as heating sources for tumour treatment by hyperthermia. Previously, we developed new iron oxide nanoparticles (IONPs) with high heating efficiencies and good clinical perspectives. However, the clinical translation of such IONPs is still hindered by a lack of understanding of certain of their features. One key issue that needs to be solved is the amount and distribution of heat at the interface between IONPs and cells. Unfortunately, this cannot be measured with currently used macroscopic temperature probes, which only give data at the bulk level. To reach the nanoscopic resolution, we combined a luminescent molecular thermometer developed at the University of Zaragoza with our IONPs. The purpose of the present work was to measure the temperature generated at the IONPs’ surface during cellular hyperthermia and to correlate the temperature with the cellular response. In order to reach that goal, IONPs were coupled to lanthanide ions (europium and terbium), which display temperature-dependent emission intensities. Lanthanide-coupled IONPs were fully characterized and their luminescent emission was calibrated as a function of temperature. Magnetic field intensities used for the calibration were those applicable to humans (H*f < 4.85*108 Am-1s-1 for a 30cm coil). Ultimately, temperatures were mapped with a high spatial resolution in a cellular assay. Cells with internalized IONPs were subjected to hyperthermia and cell death was studied. Such assays were repeated with different cell lines and different IONPs’ concentrations. In summary, this work proves the feasibility of using a molecular thermometer to characterize the heat generated around IONPs during cellular hyperthermia, addressing a recurrent problem in the field. This precise information sets the ground to further improve the therapeutic efficacy of IONPs while simultaneously minimizing the thermally induced damages to the surrounding healthy tissue.