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 H₂ O₂ . 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 H₂ O and reduction of H₂ O₂ , which consequently increases hydroxyl radical (·OH) yield even under low H₂ O₂ levels. Moreover, acceptor doping induces electron-rich oxygen vacancies to facilitate the dissociation of H₂ O₂ and H₂ 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.