Defect Engineering of Bi₂S3-x@PDA/CuS Z-Scheme Heterojunction for Enhanced Sonodynamic and Chemodynamic Cancer Therapy.

Although bismuth sulfide (Bi₂S₃) 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 Bi₂S3-x@PDA/CuS (BPC) Z-scheme heterojunction is rationally designed by coating Bi₂S3-x nanorods with polydopamine (PDA) (denoted as Bi₂S3-x@PDA) via in situ polymerization of dopamine hydrochloride and CuS nanoparticles growing on the Bi₂S3-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 Bi₂S₃, 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.