Antitumoral effect of in vivo Magnetic Hyperthermia

Abstract

[Introduction]: Magnetic Hyperthermia (MH) has been proved as an efficient treatment against tumours but still presents some drawbacks such as the limitations of the alternating magnetic field (AMF) generation sources or the need to achieve high concentrations of Magnetic Nanoparticles (MNPs) in the target tissue. Here, we present two different approaches of in vivo MH treatment with the same tumour model but different heating generation materials, combining one of them with a chemotherapeutic agent release such as doxorubicin. The results show, in both of them, an inhibition in the tumour growth. [Materials and Methods]: The animal model used consisted of an allograft and heterotopic tumour model, where EL4 murine lymphoma cell line from the strain C57BL/6N was injected subcutaneously in the right flank of immunocompetent C57BL/6 mice. One week after the cell injection the MNPs were administered intratumorally and the same day and two consecutive days MH was performed. Each exposure time was 30 min at 105 kHz and 18 kA·m-1. The first material that was used consisted of iron oxide nanoparticles (IONP) of 12nm synthetized by thermal decomposition, coated with an amphiphilic polymer (PMAO) and functionalize with Glucose to provide stability in biological fluids and to promote cell internalization. The second type of material consisted of a silica mesoporous matrix that contains IONP and doxorubicin. The silica particles were coated with a thermosensitive polymer with a Lower Critical Solution Temperature (LCST) of 42ºC2. Tumour dimensions (length, with and height) and mice weight were daily measured with a Vernier. After the last AMF exposure mice were maintained 3 days or until tumours started to ulcerate. MH treatments were made in group of 5 mice each, and all the needed control groups to validate the treatment were performed. [Results]: In both cases, 48h after the last magnetic hyperthermia treatment an inhibitory effect in the tumour growth was observed. Confocal microscopy images of the tumour revealed a good penetration of the material in both approaches. In the case of silica mesoporous material, it is noteworthy that none of the two control, where the effect of the free doxorubicin and the effect of the heat released by the MNPs due to the AMF exposition were analysed as single treatments, showed antitumor effect. However, a synergistic effect of the combination of both treatments was achieved.