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

Abstract

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.