1. Thermoresponsive Iron Oxide Nanocubes for an Effective Clinical Translation of Magnetic Hyperthermia and Heat-Mediated Chemotherapy
- Author
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Federica Marinaro, Binh T. Mai, Dina Niculaes, Preethi Bala Balakrishnan, Soraia Fernandes, Roberto Cingolani, Federica Piccardi, Alberto Curcio, Florence Gazeau, Markus J. Barthel, Gwennhael Autret, Teresa Pellegrino, Hamilton Kakwere, Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Istituto Italiano di Tecnologia (IIT), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
- Subjects
Biodistribution ,magnetic hyperthermia, thermoresponsive polymer, drug delivery, cancer therapy, combined chemotherapy, doxorubicin ,Materials science ,Cell Survival ,Polymers ,Ultraviolet Rays ,[SDV]Life Sciences [q-bio] ,Transplantation, Heterologous ,thermoresponsive polymer ,Mice, Nude ,Kaplan-Meier Estimate ,02 engineering and technology ,combined chemotherapy ,010402 general chemistry ,Ferric Compounds ,doxorubicin ,01 natural sciences ,Mice ,Cell Line, Tumor ,Neoplasms ,Ultraviolet light ,medicine ,Animals ,Humans ,[CHIM]Chemical Sciences ,Tissue Distribution ,General Materials Science ,Doxorubicin ,magnetic hyperthermia ,Magnetite Nanoparticles ,ComputingMilieux_MISCELLANEOUS ,Drug Carriers ,Combination chemotherapy ,Hyperthermia, Induced ,[CHIM.MATE]Chemical Sciences/Material chemistry ,021001 nanoscience & nanotechnology ,Magnetic Resonance Imaging ,Nanostructures ,0104 chemical sciences ,Oncothermia ,Magnetic hyperthermia ,drug delivery ,Drug delivery ,cancer therapy ,Magnetic nanoparticles ,0210 nano-technology ,Research Article ,Biomedical engineering ,medicine.drug - Abstract
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 coppermediated 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).
- Published
- 2019
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