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 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 3 (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. This article is protected by copyright. All rights reserved.