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 Ca^(2+) 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,CaO_(2)-coated Fe_(3)O_(4)core–shell magnetic nanoenzymes(Fe_(3)O_(4)/CaO_(2))are developed for low frequency vibrating magnetic field(VMF)-induced multimodal cancer therapy.Fe_(3)O_(4)/CaO_(2)are shown to efficiently generate O_(2),H_(2)O_(2),·OH through hydrolysis of CaO_(2)and a CaO_(2)-strengthened Fenton reaction,killing laryngeal carcinoma cells and inhibiting mouse tumor growth(chemodynamic therapy(CDT)).Both Fe_(3)O_(4)and Fe_(3)O_(4)/CaO_(2)triggered by a VMF are shown to damage the cytoskeleton of cancer cells through magneto-mechanical force(maxima:223 piconewtons or larger by Fe_(3)O_(4)/CaO_(2)aggregations)and induce the generation of intracellular reactive oxygen species(ROS),the VMF-triggered Fe_(3)O_(4)/CaO_(2)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 Fe_(3)O_(4)/CaO_(2)through CDT,magnetomechanical force,force-induced ROS,the cytotoxicity of Ca^(2+)ions.In addition,the Fe_(3)O_(4)/CaO_(2)nanoenzymes and VMFinduced 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.