Ultrasound-Driven Hollow Nanospheres for Amplified Tumor Oxidative Stress Therapy.

Oxidative stress therapy holds great potential owing to its noninvasive nature and high selectivity; however, its efficacy is largely limited by the hypoxic and antioxidative tumor microenvironment (TME). Herein, Ru-doped zinc peroxide (RZO) hollow nanospheres are developed for amplified tumor oxidative stress therapy under US activation. Ru doping optimizes the band structure of ZnO2 and enhances charge separation efficiency. Under US activation, the piezoelectric polarization of RZO promotes the generation of superoxide (·O2 -) and hydroxyl radicals (·OH), while the in situ-produced H2O2 under mildly acidic conditions facilitates ·OH formation. These synergistic processes induce a cascade of "reactive oxygen species (ROS) storms," leading to mitochondrial damage and apoptosis. In vitro studies demonstrate that RZO-mediated oxidative stress therapy effectively suppresses both 4T1 breast adenocarcinoma and SCC-9 squamous carcinoma cells, while in vivo experiments confirm remarkable tumor inhibition with negligible systemic toxicity. This work proposes a universal and controllable amplification strategy, offering a promising nanoplatform for precise tumor oxidative stress therapy.