In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

Abstract

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 non-invasive 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 sub-cutaneously with Matrigel™ to generate so called pseudo tumors. 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 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles 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 non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

Tuning Sizes, Morphologies, and Magnetic Properties of Monocore Versus Multicore Iron Oxide Nanoparticles through the Controlled Addition of Water in the Polyol Synthesis

“…Therapeutic hyperthermia requires that IONPs heat cancerous tissues up to 43−44 °C to deposit a suitable "thermal dose", usually by IONP intratumoral injection. 28 This temperature may potentially be reached in vivo with the best heating samples after a few minutes, even at a concentration as low as the one used in our study (3 g L −1 ), assuming that their heating properties are preserved under physiological intracellular conditions. 29 The heating properties of our sample library were thus quantified using the specific absorption rate (SAR), which was determined experimentally using the commonly used formula…”

In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

“…Figure 3 D illustrates HSP70 -dependent LucF expression as revealed by BLI. As controls, MTNs were applied on the mouse skin without magnetic field or the mouse was placed into the magnetic field for 10 min without MTNs; in these cases, no BLI signal was detected [ 25 ].…”

“…Transgenic mice with Matrigel™ pseudotumors containing MTNs without AMF application or with Matrigel™ pseudotumors alone and placed in the AMF did not exhibit BLI signal. Mice bearing pseudotumors with MTN concentrations lower than 35 g/L did not exhibit BLI signal (11 g/L, 15 min AMF on; 15 g/L 15 min AMF on; 18 g/L 15 min AMF on; n = 5; [ 25 ]).…”

Data on iron oxide core oil-in-water nanoemulsions for atherosclerosis imaging

“…NPs of 11 nm were obtained using size sorting procedure according to Sandre and al. [3]. Hydrophobization of these NPs was performed by complexation of OA on the SPION surface according to the procedure described by Van Ewijk et al [4] .…”