Analyzing ROS Generation From Magnetic Nanoparticles In An Alternating Magnetic Field and Its Role In Intracellular Hyperthermia

Through Brownian relaxation and Neel relaxation, magnetic nanoparticles are capable of absorbing energy from an alternating magnetic field (AMF) and converting it to heat. Thus, via passive targeting, nanoparticles can collect at the tumor site and by the application of an AMF provide localized heating throughout the tumor.  Furthermore, internalized targeted nanoparticles have been recently shown to induce cellular death when exposed to an AMF without a measurable temperature rise, therefore stimulating great interest to develop targeted nanoparticles for the treatment of metastatic cancer via intracellular hyperthermia.  Focusing on the iron oxide magnetic nanoparticle system, it is thought that at the molecular level a significant contributing factor to the iron oxide toxicity in intracellular hyperthermia is the generation of reactive oxygen species (ROS) through the Fenton and Haber Weiss reactions.  This research, in turn, focuses on the effects of an AMF on the surface mediated production of ROS based on the hypothesis that these effects are a key contributor to the toxicity demonstrated as intracellular hyperthermia.  Despite variance in temperature ranging 37-39°C, it was observed via the methylene blue dye degradation method that samples exposed to an AMF experienced increased ROS production.  Moreover, the Arrhenius equation, , where  s^-1 and J, was determined from a series of kinetic studies.  This equation showed that despite variability in heating profile, experimental values of dye degradation were consistently lower than the theoretical values indicating improved kinetics due to AMF exposure.  Furthermore, AMF data points did not fit the derived Arrhenius trendline strongly suggesting that AMF mediated heating possesses a kinetic effect unique to that of bulk heating.  Preliminary cell culture studies conducted by means of the viability-ROS assay suggested that as uncoated iron oxide magnetic nanoparticle concentration increases, ROS generation increases and cell viability decreases.