Ultrasound-Driven Non-Metallic Fenton-Active Center Construction for Extensive Chemodynamic Therapy

Chemodynamic therapy (CDT) is an emerging tumor microenvironment-responsive cancer therapeutic strategy based on Fenton/Fenton-like reactions. However, the effectiveness of CDT is subject to the slow kinetic rate and non-homogeneous distribution of H2O2. In this study, a conceptual non-metallic "Fenton-active" center construction strategy is proposed to enhance CDT efficiency using Bi0.44Ba0.06Na0.5TiO2.97 (BNBT-6) nanocrystals. The separated charge carriers under a piezoelectric-induced electric field synchronize the oxidation of H2O and reduction of H2O2, which consequently increases hydroxyl radical (center dot OH) yield even under low H2O2 levels. Moreover, acceptor doping induces electron-rich oxygen vacancies to facilitate the dissociation of H2O2 and H2O and further promote center dot OH generation. In vitro and in vivo experiments demonstrate that BNBT-6 induces extensive intracellular oxidative stress and enhances cell-killing efficiency by activating necroptosis in addition to the conventional apoptotic pathway. This study proposes a novel design approach for nanomaterials used in CDT and presents a new treatment strategy for apoptosis-resistant tumors. A non-metallic "Fenton-active" center construction strategy is proposed to catalyze the decomposition of H2O2 and H2O and enhance center dot OH yield using Bi0.44Ba0.06Na0.5TiO2.97 nanocrystals. The built-in electric field and electron-rich oxygen vacancies promote center dot OH yield even in the tumor area with a low H2O2 concentration, resulting in extensive cellular damage and enhanced cell-killing efficiency by activating the necroptosis pathway.image