Design Maps for the Hyperthermic Treatment of Tumors with Superparamagnetic Nanoparticles

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. Here, we study the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs), with core diameter of 5, 7 and 14 nm, in terms of absolute temperature increase Delta T and specific absorption rate (SAR). These nanoparticles are operated under a broad range of AMF conditions, with frequency f varying between 0.2 and 30 MHz; field strength H ranging from 4 to 10 kA m(-1); and concentration c(MNP) varying from 0.02 to 3.5 mg ml(-1). At high frequency field (similar to 30 MHz), non specific heating dominates and Delta T correlates with the electrical conductivity of the medium. At low frequency field (<1 MHz), non specific heating is negligible and the relaxation of the SPIO within the AMF is the sole energy source. We show that the Delta T of the medium grows linearly with c(MNP), whereas the SAR(MNP) of the magnetic nanoparticles is independent of c(MNP) and varies linearly with f and H-2. Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (T-tissue >42 degrees C) and thermal ablation (T-tissue >50 degrees C) are derived in terms of c(MNP), operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration - systemic versus intratumor injection - depending on the magnetic and biodistribution properties of the nanoparticles.