Exploring magnetic hyperthermia: ferrofluids, in vitro and in vivo experiments

D. CORAL; P. SOTO; V. BLANK; A. VEIGA

Gramado

Workshop; XVI Brazilian Materials Research Society Meeting; 2017

Materials Research Society

New therapeutic and diagnosis methodologies based in nanotechnology are of great importance nowadays. These protocols are meant be less invasive, more efficient and displaying minor side effects, being endow of selectivity. Magnetic hyperthermia, a modality that uses radio frequency heating of single-domain magnetic nanoparticles, is becoming established as a powerful oncological therapy. Regarding citotoxicity, viability and clearance, iron oxide nanoparticles (IONPs) are the most biocompatible materials and have been accepted as a medical device. Magnetic hyperthermia has reached clinical trial stage, but there are still unsolved basic problems related to: dosage; nanoparticles spatial distribution in target tissue and related temperature distribution; temperature monitoring and its increase control. Dosage is mainly determined by the nanoparticles´s efficiency to transduced heat, characterized by the specific absorption rate (SAR). But, this efficiency depends on magnetic relaxation mechanism and it is highly influence by nanoparticle size and its dispersity, aggregation, interaction, and it is further modify by cell internalization, restricted mobility and confinement inside tumour environment. To address these problems, in the last years we have performed radio frequency heating experiments, going from ferrofluids synthesis and optimization [1, 2] to in vitro [3] and more recent in vivo assays. In this presentation we will review our results. We have analyzed aqueous dispersion of IONPs, designed to be single particle, core/shell, random multicore and magnetically organized multicore systems. We have proved that the relevant physical parameter for predicting fluid SAR are mean nanoparticle volume, its saturation magnetization and a representative mean activation energy and that SAR parameter depends on concentration [3], [4], a fact that has to be taken into account to established optimum dosage. In vitro experiments were used to determined cellular uptake, intracellular particle distribution, cytotoxicity and to develop a new methodology for probing intracellular heating in cells cultures[3]. In vivo experiments constitute an even more complex scenario because after intratumoral infiltration irregular distribution patterns of the magnetic materials occur due to high interstitial pressures. Recent results mice tumor models will be discussed. Also we will present a brief description of a device, based on a parallel LC resonant circuit optimized to generate alternating magnetic fields of 100 kHz frequency and amplitude adjustable from 2 to 15 kA/m, versatile tool for research involving the use of magnetic materials and alternating magnetic field for fighting cancer, like magnetic hyperthermia and drug and gene delivery triggered by magnetic stimuli[5].