title: In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia.
abstract: The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.
authors.affiliation: Laboratory of Organic Polymer Chemistry, LCPO, UMR 5629 CNRS, University of Bordeaux, Bordeaux-INP, Pessac 33600, France. olivier.sandre@enscbp.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sandre
authors.affiliation: Molecular Imaging and Innovative Therapies in Oncology, IMOTION, EA 7435, University of Bordeaux, 146 rue Léo Saignat, case 127, Bordeaux cedex 33076, France. coralie.genevois@u-bordeaux.fr.
authors.forename: Coralie
authors.initials: C
authors.lastname: Genevois
authors.affiliation: Department of Electricity and Electronics, University of the Basque Country (UPV/EHU), P.K. 644, Leioa 48940, Spain. eneko.garayo@ehu.eus.
authors.forename: Eneko
authors.initials: E
authors.lastname: Garaio
authors.affiliation: Institute for Condensed Matter Chemistry of Bordeaux, ICMCB, UPR 9048, CNRS, University of Bordeaux, Pessac F-33600 France. laurent.adumeau@gmail.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Adumeau
authors.affiliation: Institute for Condensed Matter Chemistry of Bordeaux, ICMCB, UPR 9048, CNRS, University of Bordeaux, Pessac F-33600 France. stephane.mornet@icmcb.cnrs.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mornet
authors.affiliation: Molecular Imaging and Innovative Therapies in Oncology, IMOTION, EA 7435, University of Bordeaux, 146 rue Léo Saignat, case 127, Bordeaux cedex 33076, France. franck.couillaud@u-bordeaux.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Couillaud
keywords: gene therapies; heat shock protein promoter; in vivo optical imaging; magnetic hyperthermia; magnetic polymer-coated nanoparticles