Oxygen and hydrogen peroxide self-supplying magnetic nanoenzymes for cancer therapy through magneto-mechanical force, force-induced reactive oxygen species, chemodynamic effects, and cytotoxicity of Ca2+ ions

The use of magneto-mechanical force to kill cancer cells has attracted significant attention in recent years. However, many reports have focused on in vitro experiments with a single treatment. Herein, CaO2-coated Fe3O4 core—shell magnetic nanoenzymes (Fe3O4/CaO2) are developed for low frequency vibrating magnetic field (VMF)-induced multimodal cancer therapy. Fe3O4/CaO2 are shown to efficiently generate O2, H2O2, and ·OH through hydrolysis of CaO2 and a CaO2-strengthened Fenton reaction, killing laryngeal carcinoma cells and inhibiting mouse tumor growth (chemodynamic therapy (CDT)). Both Fe3O4 and Fe3O4/CaO2 triggered by a VMF are shown to damage the cytoskeleton of cancer cells through magneto-mechanical force (maxima: 223 piconewtons or larger by Fe3O4/CaO2 aggregations) and induce the generation of intracellular reactive oxygen species (ROS), and the VMF-triggered Fe3O4/CaO2 is shown to generate additional intracellular ROS. Upon exposure to a VMF, the cell killing efficiency and tumor growth inhibition were further significantly improved by Fe3O4/CaO2 through CDT, magnetomechanical force, force-induced ROS, and the cytotoxicity of Ca2+ ions. In addition, the Fe3O4/CaO2 nanoenzymes and VMF-induced treatment are shown to be safe for mice. The results of this study open the door for treating solid tumors without inducing multidrug resistance through the combination of CDT and force.