Theranostics 2017; 7(18):4618-4631. doi:10.7150/thno.18927 This issue

Research Paper

Enhanced antitumor efficacy of biocompatible magnetosomes for the magnetic hyperthermia treatment of glioblastoma

Raphaël Le Fèvre1, 2, Mickaël Durand-Dubief1, Imène Chebbi1, Chalani Mandawala1, 3, France Lagroix2, Jean-Pierre Valet2, Ahmed Idbaih5, Clovis Adam6, Jean-Yves Delattre5, Charlotte Schmitt5, Caroline Maake4, François Guyot3, Edouard Alphandéry1,3✉

1. Nanobacterie SARL, 36 boulevard Flandrin, 75016, Paris.
2. Institut de Physique du Globe de Paris, Sorbonne Paris Cité, Univ. Paris Diderot, UMR 7154 CNRS, 1 rue Jussieu, 75005 Paris, France.
3. Institut de minéralogie de physique des matériaux et de cosmochimie, Sorbonne Université UMR 7590 CNRS, Université Pierre et Marie Curie, Muséum Naitonal d'Histoire Naturelle. 4 Place Jussieu, 75005, Paris, France.
4. Institute of Anatomy, UZH University of Zurich, Instiute of Anatomy, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
5. Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC, University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France. AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, F-75013, Paris, France.
6. Laboratoire de neuropathologie, GHU Paris-Sud-Hôpital Bicêtre, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France.

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Citation:
Le Fèvre R, Durand-Dubief M, Chebbi I, Mandawala C, Lagroix F, Valet JP, Idbaih A, Adam C, Delattre JY, Schmitt C, Maake C, Guyot F, Alphandéry E. Enhanced antitumor efficacy of biocompatible magnetosomes for the magnetic hyperthermia treatment of glioblastoma. Theranostics 2017; 7(18):4618-4631. doi:10.7150/thno.18927. Available from https://www.thno.org/v07p4618.htm

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Abstract

Graphic abstract

In this study, biologically synthesized iron oxide nanoparticles, called magnetosomes, are made fully biocompatible by removing potentially toxic organic bacterial residues such as endotoxins at magnetosome mineral core surfaces and by coating such surface with poly-L-lysine, leading to magnetosomes-poly-L-lysine (M-PLL). M-PLL antitumor efficacy is compared with that of chemically synthesized iron oxide nanoparticles (IONPs) currently used for magnetic hyperthermia. M-PLL and IONPs are tested for the treatment of glioblastoma, a dreadful cancer, in which intratumor nanoparticle administration is clinically relevant, using a mouse allograft model of murine glioma (GL-261 cell line). A magnetic hyperthermia treatment protocol is proposed, in which 25 µg in iron of nanoparticles per mm3 of tumor are administered and exposed to 11 to 15 magnetic sessions during which an alternating magnetic field of 198 kHz and 11 to 31 mT is applied for 30 minutes to attempt reaching temperatures of 43-46 °C. M-PLL are characterized by a larger specific absorption rate (SAR of 40 W/gFe compared to 26 W/gFe for IONPs as measured during the first magnetic session), a lower strength of the applied magnetic field required for reaching a target temperature of 43-46 °C (11 to 27 mT compared with 22 to 31 mT for IONPs), a lower number of mice re-administered (4 compared to 6 for IONPs), a longer residence time within tumours (5 days compared to 1 day for IONPs), and a less scattered distribution in the tumour. M-PLL lead to higher antitumor efficacy with full tumor disappearances achieved in 50% of mice compared to 20% for IONPs. This is ascribed to better ability of M-PLL, at equal iron concentrations, to maintain tumor temperatures at 43-46°C over a longer period of times.

Keywords: Glioblastoma, nanomedicine, magnetic hyperthermia, alternating magnetic field, magnetotactic bacteria, magnetosomes