Bottle Nanomotors Amplify Tumor Oxidative Stress for Enhanced Calcium Overload/Chemodynamic Therapy

Abstract Developing multifunctional, stimuli‐responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen‐driven silicon‐based nanomotor (Si‐motor) loaded with MnO and CaO 2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO 2 and MnO. Under acidic TME, CaO 2 reacts with acid to release Ca 2+ to induce mitochondrial damage and simultaneously produces O 2 and H 2 O 2 , when the loaded MnO exerts Fenton‐like activity to produce ·OH and O 2 based on the produced H 2 O 2 . The generated O 2 drives Si‐motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si‐motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca 2 + overloading, GSH depletion induced by Mn 2+ , and Mn 2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.