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, magneto-mechanical 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.