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

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 CaO₂ nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO₂ and MnO. Under acidic TME, CaO₂ reacts with acid to release Ca²⁺ to induce mitochondrial damage and simultaneously produces O₂ and H₂O₂, when the loaded MnO exerts Fenton-like activity to produce ·OH and O₂ based on the produced H₂O₂. The generated O₂ 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 Mn²⁺, and Mn²⁺ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.