Abstract
Magnetic nanoparticles (MNPs) are capable of generate heating power under the influence of alternating magnetic fields (AMF); this behaviour recently opened new scenarios for advanced biomedical applications, mainly as new promising tumor therapies. In this paper we have tested magnetic nanoparticles called magnetosomes (MNs): a class of MNPs naturally produced by magnetotactic bacteria. We extracted MNs from Magnetospirillum gryphiswaldense strain MSR-1 and tested the interaction with cellular elements and anti-neoplastic activity both in vitro and in vivo, with the aim of developing new therapeutic approaches for neoplastic diseases. In vitro experiments performed on Human Colon Carcinoma HT-29 cell cultures demonstrated a strong uptake of MNs with no evident signs of cytotoxicity and revealed three phases in the interaction: adherence, transport and accumulation in Golgi vesicles. In vivo studies were performed on subcutaneous tumors in mice; in this model MNs are administered by direct injection in the tumor volume, then a protocol consisting of three exposures to an AMF rated at 187 kHz and 23kA/m is carried out on alternate days, over a week. Tumors were monitored by Magnetic Resonance Imaging (MRI) to obtain information about MNs distribution and possible tissue modifications induced by hyperthermia. Histological analysis showed fibrous and necrotic areas close to MNs injection sites in mice subjected to a complete thermotherapy protocol. These results, although concerning a specific tumor model, could be useful to further investigate the feasibility and efficacy of protocols based on MFH. Magnetic nanoparticles naturally produced and extracted from bacteria seem to be promising candidates for theranostic applications in cancer therapy.
Highlights
Thermotherapy represents an effective tool for the treatment of many types of tumor but it is strongly hampered by poor specificity of the induced lesion [1,2,3]
Several approaches have been proposed to improve the efficacy of the technique: one of them is based on intratumoral delivery of magnetic nanoparticles (MNPs) followed by application of alternating magnetic fields (AMF) to increase the local temperature of the tissue the effectiveness of the method [3,4,5]
Morphology and physical properties of MNs Transmission electron microscopy (TEM) of whole-mount bacteria, observed by backscattered electron detector, showed that MNs are organized in long chains (Figure 1a) along the major axis of each bacterium
Summary
Thermotherapy represents an effective tool for the treatment of many types of tumor but it is strongly hampered by poor specificity of the induced lesion [1,2,3]. Several approaches have been proposed to improve the efficacy of the technique: one of them is based on intratumoral delivery of magnetic nanoparticles (MNPs) followed by application of alternating magnetic fields (AMF) to increase the local temperature of the tissue the effectiveness of the method [3,4,5]. In 1963, the Italian scientist Salvatore Bellini reported the first description of magnetotactic bacteria. This subtype of organisms naturally produces magnetic iron-oxide nanoparticles and uses them as a compass for geomagnetic navigation to search for optimal growth conditions [6,7]; those nanoparticles have been over time referred as magnetosomes (MNs). A more complete description of magnetotactic bacteria was later reported [8]
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