Single‐Atom W Anchored Hexagonal Boron Nitride Piezoelectric Nanosonosensitizer Remodels Tumor Microenvironment for Enhanced Sonodynamic Therapy

Abstract Sonodynamic therapy (SDT) is a non‐invasive, non‐toxic technique that shows strong potential for tumor treatment: however, its application is limited by a lack of efficient sonosensitizers, insufficient oxygen supply, and high levels of glutathione (GSH) in tumors. In this study, a nanosonosensitizer, single‐atom W anchored hexagonal boron nitride@ferrihydrite@trisulfide bond‐modified carboxymethyl chitosan (W‐BN@Fht@TSCM) nanocomplex, is developed that exhibits an efficient sonosensitizing effect and tumor microenvironment remodeling ability, thereby enhancing SDT. W‐BN is prepared by anchoring monatomic W onto the surface of hexagonal boron nitride (h‐BN) nanosheets, which exhibit a superior piezoelectric response to that of h‐BN owing to the breaking of lattice symmetry. This excellent piezoelectric response facilitates the production of more reactive oxygen species under ultrasound conditions. Moreover, H 2 O 2 in the tumor microenvironment is decomposed to O 2 by Fht nanoparticles, which serve as catalase‐like nanoenzymes, thereby alleviating hypoxia and providing sufficient substrates. Additionally, TSCM, which provides three unique redox sites and exhibits a high redox potential, rapidly and efficiently consumes GSH, weakens the antioxidant defense mechanism of tumor cells and enhances the efficacy of SDT. Improving the piezoelectric response of the material while remodeling the tumor microenvironment demonstrates strong therapeutic effects and provides a reference for the design of SDT nanosystems.