Institut de minéralogie et de physique des milieux condensés de physique des matériaux et de cosmochimie, UMR 7590 CNRS, Sorbonne Universités, UPMC, University Paris 06, Muséum National d'Histoire Naturelle, 4 Place Jussieu, 75005 Paris, France; Nanobacterie SARL, 36 boulevard Flandrin, 75016 Paris, France.
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.
J Control Release. 2017 Sep 28;262:259-272. doi: 10.1016/j.jconrel.2017.07.020. Epub 2017 Jul 13.
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 13μg of nanoparticles per mm of tumor followed by 12 to 15 of 30min 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.
先前的研究表明,磁热疗在临床前和临床水平上都能有效地破坏肿瘤,尤其是神经胶质瘤。然而,抗肿瘤疗效仍然不理想,因此需要进一步改进。在这里,我们介绍一种新型的纳米粒子,由趋磁细菌合成,称为磁小体,与常用的化学合成纳米粒子相比,具有更好的性能。确实,在颅内 U87-Luc 神经胶质瘤肿瘤中注射 13μg 每毫米肿瘤的纳米粒子,随后进行 12 到 15 次 30 分钟的交变磁场应用,在使用磁小体或化学合成纳米粒子的情况下,分别有 40%的小鼠出现完全肿瘤消失或无肿瘤消退。磁小体具有更强的抗肿瘤活性,这可以解释为在交变磁场应用下产生了更多的热量和内毒素释放。最有趣的是,当磁小体仅占据整个肿瘤体积的 10%时,就观察到了这种行为,这表明一种间接机制,如免疫反应,参与了肿瘤的消退。这对于治疗浸润性肿瘤(如神经胶质瘤)是理想的,因为很难用纳米粒子覆盖整个肿瘤。
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