Magnetic hyperthermia therapy (MHT) has been considered as an excellent alternative for treatment of deep tumor tissue; however, up-regulation of heat shock proteins (HSPs) impairs its hyperthermal therapeutic effect. Reactive oxygen species (ROS) and competitive consumption of ATP are important targets that can block excessive HSP generation. We developed a magnetic nanocatalytic system comprised of glucose oxidase (GOD)-loaded hollow iron oxide nanocatalysts (HIONCs) to drive starvation-chemodynamic-hyperthermia synergistic therapy for tumor treatment. The Fe2+ present in HIONCs contributed to ROS generation via the Fenton reaction, relieving thermo-resistance and inducing cell apoptosis by chemodynamic action. The Fenton effect was enhanced through the conditions created by increased MHT-related temperature, GOD-mediated H2O2 accumulation, and elevated tumor microenvironment acidity. The HIONCs catalase-like activity facilitated conversion of H2O2 to oxygen, thereby replenishing the oxygen levels. We further demonstrated that locally injected HIONCs-GOD effectively inhibited tumor growth in PC3 tumor-bearing mice. This study presents a multifunctional nanocarrier system driving starvation-chemodynamic-magnetic-thermal synergistic therapy via ROS and oxygen modulation for prostate tumor treatment.
Keywords: Fenton reaction; heat shock proteins; magnetic hyperthermal therapy; reactive oxygen species; starvation therapy; tumor hypoxia.