| Autor: |
Mai BT; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy.; Dipartimento di Chimica e Chimica Industriale , Università di Genova , Via Dodecaneso, 31 , 16146 Genova , Italy., Balakrishnan PB; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy.; Dipartimento di Chimica e Chimica Industriale , Università di Genova , Via Dodecaneso, 31 , 16146 Genova , Italy., Barthel MJ; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy., Piccardi F; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy., Niculaes D; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy.; Dipartimento di Chimica e Chimica Industriale , Università di Genova , Via Dodecaneso, 31 , 16146 Genova , Italy., Marinaro F; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy., Fernandes S; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy., Curcio A; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy., Kakwere H; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy., Autret G; Centre de Recherche Cardiovasculaire de Paris 56 , rue Leblanc , 75737 Paris Cedex 15 , France., Cingolani R; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy., Gazeau F; Laboratoire Matière et Systèmes Complexes , UMR 7057, CNRS and University Paris Diderot , 75205 Paris Cedex 13 , France., Pellegrino T; Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy. |
| Abstrakt: |
The use of magnetic nanoparticles in oncothermia has been investigated for decades, but an effective combination of magnetic nanoparticles and localized chemotherapy under clinical magnetic hyperthermia (MH) conditions calls for novel platforms. In this study, we have engineered magnetic thermoresponsive iron oxide nanocubes (TR-cubes) to merge MH treatment with heat-mediated drug delivery, having in mind the clinical translation of the nanoplatform. We have chosen iron oxide based nanoparticles with a cubic shape because of their outstanding heat performance under MH clinical conditions, which makes them benchmark agents for MH. Accomplishing a surface-initiated polymerization of strongly interactive nanoparticles such as our iron oxide nanocubes, however, remains the main challenge to overcome. Here, we demonstrate that it is possible to accelerate the growth of a polymer shell on each nanocube by simple irradiation of a copper-mediated polymerization with a ultraviolet light (UV) light, which both speeds up the polymerization and prevents nanocube aggregation. Moreover, we demonstrate herein that these TR-cubes can carry chemotherapeutic doxorubicin (DOXO-loaded-TR-cubes) without compromising their thermoresponsiveness both in vitro and in vivo. In vivo efficacy studies showed complete tumor suppression and the highest survival rate for animals that had been treated with DOXO-loaded-TR-cubes, only when they were exposed to MH. The biodistribution of intravenously injected TR-cubes showed signs of renal clearance within 1 week and complete clearance after 5 months. This biomedical platform works under clinical MH conditions and at a low iron dosage, which will enable the translation of dual MH/heat-mediated chemotherapy, thus overcoming the clinical limitation of MH: i.e., being able to monitor tumor progression post-MH-treatment by magnetic resonance imaging (MRI). |
