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Accueil du site > LPCNO > Séminaires > 2016 > Dendritic cells therapy using magnetic hyperthermia

Dendritic cells therapy using magnetic hyperthermia

Date : 13/12/2016 à 14:00

Titre : Dendritic cells therapy using magnetic hyperthermia

Intervenant : Ricardo Ibarra

Provenance : Nanoscience Institute of Aragon (INA), Laboratory of advanced Microscopies (LMA), Fundation of the Institute of Nanoscience of Aragón, University of Zaragoza, 50009 - Zaragoza, Spain.

Salle : Salle se séminaire - LPCNO

Résumé : Magnetic nanoparticles (MNPs) constitute nowadays a vast field of research due to the current and expected application in nanomedicine. The potential of MNPs stems from the intrinsic properties of their magnetic cores, combined with the functionality acquired under an appropriate coating. The capability for loading, targeting and controlled release of drugs is one of the main issues in cancer therapy (for recent reviews see [1,2]). The biofunctionalization of the nanoparticles surface make them suitable for magnetic separation based on the bio-molecular recognition of biological moieties. New inmunomagnetic assays using magnetic nanoparticles provides a new route to quantize the results in biosensors. The presence of MNPs also perturb locally the hydrogen proton relaxation, this phenomenon is on the bases of the enhance MRI diagnostic using contrast agents. Targeting of these contrast agents could detect angiogenesis processes at early stages.

Dendritic cells (DCs) are antigen-presenting cell to T cells and play a key role in the immune system. I addition, as immature cells, they are installed at tumor place. This opens new avenues for immunotherapy against tumours based in DCs cancer vaccines and constitutes a relevant issue for targeting of magnetic nanoparticles via cell migration.

Magnetic hyperthermia (MH) is based on the use of MNPs to selectively increase the temperature of MNP-loaded target tissues when applying an alternating magnetic field (AMF) in the range of radiofrequency. To date, all MH research has focused on heat generation in an attempt to elucidate the mechanisms for the death of MNP-loaded cells submitted to AMF. However, recent in vitro studies have demonstrated the feasibility of inducing dramatic cell death without increasing the macroscopic temperature during AMF exposure. We show that the MNPs loaded DCs death observed following AMF exposure, was caused by the release of toxic agents into the cell culture supernatants and not due to a macroscopic temperature increase.[3] Our results demonstrate that heat is not the only agent responsible for triggering cell death following MH treatment. This finding offers new perspectives for the use of DCs as the targeting agent for MNPs to reach the tumour area and these results further support the use of DCs as therapeutic agents against cancer when submitted to AMF. Furthermore, this discovery may help in understanding the mechanism of cell death mediated by exposure to AMF.

Induced effects by direct exposure to ionizing radiation (IR) are a central issue in many fields like radiation protection, clinic diagnosis and oncological therapies. Direct irradiation at certain doses induces cell death, but similar effects can also occur in cells no directly exposed to IR, a mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce also the death of cells loaded with magnetic nanoparticles (MNPs) in a focused oncological therapy. Indirect mechanisms are also able to induce the death of unloaded MNPs cells. Using in vitro cell models, we found that co-localization of the MNPs at the lysosomes and the non-increase of the temperature induces bystander effect under non-IR. Our results provide a landscape in which bystander effects are a more general mechanism, up to now only observed and clinically used, in the field of radiotherapy.

[1] Magnetic nanoparticles for drug delivery” M. Arruebo, R. Fernandez-Pacheco, M.R. Ibarra and J. Santamaría. Nanotoday 2 (2007) 22
[2] Magnetic nanoparticles for cancer therapy” G.F : Goya, V. Grazu and M.R. Ibarra. Current Nanoscience 4 (2008) 1-16
[3] Induced cell toxicity originates dendritic cell death following magnetic hyperthermia treatment” L Asín, G F Goya, A Tres & M R Ibarra Cell Death and Disease 4, e596 doi:10.1038/cddis.2013.121 ( )