Magnetite Nanoparticles for Cell Lysis Implanted Into Bone - Histological and TEM Study

Abstract

Magnetite nanoparticles are frequently used to eliminate by heating in a high frequence oscillating magnetic field the tumor cells into which they are introduced in order to directly kill the cells or to make them more sensitive to radiotherapy (Ito, A., et al., 2005; Jordan, A., et al., 2001). The appearance of bone metastases is a sign of a dissemination of primitive cancers. They rapidly become resistant to chemotherapy and radiotherapy and are often very painful necessitating local and/or alternative treatments in order to reduce the osteolysis triggered by the cancerous cells. The osteolysis is due to local activation of the osteoclasts and macrophages by factors synthesized by the tumor cells (Shimamura, T., et al., 2005). It is the osteolysis that is very often responsible for the pain. We have developed a biomaterial containing magnetite nanoparticles which can be introduced into bone metastases in order to release naked nanoparticles in the contact with both the cancerous and the osteolytic cells. The material is made of a calcium sulphate paste containing a small percentage of nanoparticles which can be injected inside the metastasis (fig. 1). It sets within a few minutes in situ. The degradation of the calcium sulphate matrix within a few days releases the nanoparticles which are then available for cell internalisation. In vitro, these particles can be internalised in high amounts by metastatic cells from adenocarcinoma. The number of nanoparticles found inside the cells depends on the nanoparticle size, however the mass internalized seems to be almost independent of their size (Frayssinet, P., et al., 2005). The nanoparticles did not show in vitro any signs of cell toxicity. This is consistent with previous reports which showed that cytotoxicity of magnetite nanoparticles could be due to several factors such as coating (Hafeli & Pauer, 1999). Furthermore, they are intented for use in very low doses (a few mgs). The degradation products of iron oxide are well known. They do not have a reported toxicity and are easily eliminated from the organism (Schoepf, U., et al. 1998, Okon, E.E., et al. 2000, Okon, F., et al. 1994). Migration of the nanoparticles can however be a cause of concern due to the possible unwanted heating of other regions of the organism when submitted to a magnetic field.