Defect Engineering of Bi ₂ S _3‐x @PDA/CuS Z‐Scheme Heterojunction for Enhanced Sonodynamic and Chemodynamic Cancer Therapy

ABSTRACT Although bismuth sulfide (Bi 2 S 3 ) with a narrow bandgap shows great promise for sonodynamic therapy (SDT), its efficacy is limited by a low reactive oxygen species (ROS) quantum yield due to the rapid recombination of electron and hole pairs. Herein, a sulfur‐vacancy‐rich Bi 2 S 3‐x @PDA/CuS (BPC) Z‐scheme heterojunction is rationally designed by coating Bi 2 S 3‐x nanorods with polydopamine (PDA) (denoted as Bi 2 S 3‐x @PDA) via in situ polymerization of dopamine hydrochloride and CuS nanoparticles growing on the Bi 2 S 3‐x @PDA surface to overcome this challenge. This design synergistically integrates sulfur‐vacancy engineering and a Z‐scheme heterostructure to regulate the electronic properties of Bi 2 S 3 , dramatically enhancing charge separation and boosting ROS production for potent SDT. Crucially, the BPC heterojunction simultaneously remodels the tumor microenvironment; it functions as a Fenton‐like nanozyme to generate hydroxyl radical ( • OH) for chemodynamic therapy while using sono‐excited holes to consume overexpressed glutathione, thereby amplifying intratumoral oxidative stress. Surface functionalization with hyaluronic acid (HA) endows the final BPC@HA nanocomposite with excellent physiological stability, biocompatibility, and active cancer‐cell targeting capabilities. As a result, in vivo studies confirmed that BPC@HA dramatically suppresses tumor growth through these combined properties. This study presents a powerful paradigm for engineering multifunctional sonosensitizers that overcome both intrinsic material limitations and extrinsic biological barriers in cancer therapy.