Chains of magnetosomes with controlled endotoxin release and partial tumor occupation induce full destruction of intracranial U87-Luc glioma in mice under the application of an alternating magnetic field

Edouard Alphandéry, Ahmed Idbaih, Clovis Adam, Jean-Yves Delattre, Charlotte Schmitt, François Guyot, Imène Chebbi

Index: 10.1016/j.jconrel.2017.07.020

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Abstract

Previous studies showed that magnetic hyperthermia could efficiently destroy tumors both preclinically and clinically, especially glioma. However, antitumor efficacy remained suboptimal and therefore required further improvements. Here, we introduce a new type of nanoparticles synthesized by magnetotactic bacteria, called magnetosomes, with improved properties compared with commonly used chemically synthesized nanoparticles. Indeed, mice bearing intracranial U87-Luc glioma tumors injected with 13 μg of nanoparticles per mm3 of tumor followed by 12 to 15 of 30 min alternating magnetic field applications displayed either full tumor disappearance in 40% of mice or no tumor regression using magnetosomes or chemically synthesized nanoparticles, respectively. Magnetosome superior antitumor activity could be explained both by a larger production of heat and by endotoxins release under alternating magnetic field application. Most interestingly, this behavior was observed when magnetosomes occupied only 10% of the whole tumor volume, which suggests that an indirect mechanism, such as an immune reaction, takes part in tumor regression. This is desired for the treatment of infiltrating tumors, such as glioma, for which whole tumor coverage by nanoparticles can hardly be achieved.