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

Abstract 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 H 2 O 2 . In this study, a conceptual non‐metallic “Fenton‐active” center construction strategy is proposed to enhance CDT efficiency using Bi 0.44 Ba 0.06 Na 0.5 TiO 2.97 (BNBT‐6) nanocrystals. The separated charge carriers under a piezoelectric‐induced electric field synchronize the oxidation of H 2 O and reduction of H 2 O 2 , which consequently increases hydroxyl radical (·OH) yield even under low H 2 O 2 levels. Moreover, acceptor doping induces electron‐rich oxygen vacancies to facilitate the dissociation of H 2 O 2 and H 2 O and further promote ·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.