Magnetosomes extracted from Magnetospirillum gryphiswaldence as magnetic thermotherapy agents

Thermotherapy represents an effective treatment for tumors. Magnetic fluid thermotherapy involves the use of iron-based magnetic nanoparticles injected into the tumor mass. In 1963 the Italian scientist, Salvatore Bellini, reported the first description of magnetotactic bacteria which naturally produce iron-nanoparticles, named magnetosomes (MN), and use them as a compass for geomagnetic navigation in search for optimal growth conditions. Recently, it has been reported that magnetosomes extracted from bacteria can be used in magnetic thermotherapy. We have extracted magnetosomes from Magnetospirillum gryphiswaldense strain MSR-1 and tested their interaction with cellular elements and their activity in vitro and in vivo with the aim to assess their usefulness as therapeutic agents in magnetic fluid hyperthermia. MNs were extracted from MSR-1, analyzed by transmission electron microscopy (TEM) and tested for toxicity on a colon carcinoma cell line (HT-29). In vivo study were performed in xenografts obtained by HT-29 cells injected subcutaneously in mice. Each tumor was treated with MNs followed by cycles of thermotherapy at 187 kHz and 40 mT. The efficacy of the treatment was assessed in vivo by magnetic resonance imaging (MRI) and ex vivo by histology. TEM showed that MNs were octahedral crystals organized in chains of about 20 nanoparticles. The length of chains depended on the parameters selected for bacterial culture. In vitro, MNs were not toxic versus HT-29 cells. The interaction between MNs and HT-29 cells, as studied by TEM, revealed three phases: adherence to and transport through cell membrane followed by accumulation in Golgi vesicles. In in vivo experiments, MNs were injected in the tumoral mass. The site of injection and tissutal distribution of magnetosomes was detected in vivo by MRI. After thermotherapy, the tumors were studied by histology and showed fibrotic and necrotic areas close to MNs accumulation sites. The time evolution of tumor mass was not significantly different from controls. TEM showed that MNs were octahedral crystals organized in chains of about 20 nanoparticles. The length of chains depended on the parameters selected for bacterial culture. In vitro, MNs were not toxic versus HT-29 cells. The interaction between MNs and HT-29 cells, as studied by TEM, revealed three phases: adherence to and transport through cell membrane followed by accumulation in Golgi vesicles. In in vivo experiments, MNs were injected in the tumoral mass. The site of injection and tissutal distribution of magnetosomes was detected in vivo by MRI. After thermotherapy, the tumors were studied by histology and showed fibrotic and necrotic areas close to MNs accumulation sites. The time evolution of tumor mass was not significantly different from controls. Our data suggest that MNs extracted from MSR-1 posses low toxicity in vitro and, after thermotherapy cycles, can induce damage in tumor tissue. The effect on total tumor mass regression was negligible, within the applied experimental conditions.