Sulfur Vacancy-Rich Bi2S3–x–Pt Heterojunction with Multi-enzymatic Activities for Enhanced Sonodynamic Therapy

Although bismuth sulfide (Bi₂S₃) possesses a narrow bandgap, advantageous for sonodynamic therapy (SDT), a substantial portion of ultrasound (US)-excited electrons is lost due to rapid electron-hole pair recombination, hindering their surface participation in redox reactions. In this study, a sulfur vacancy engineering strategy was implemented to yield Bi₂S_3-x with in situ-generated abundant sulfur vacancies, which significantly enhanced electron-hole pair separation for reactive oxygen species (ROS) production under US irradiation. Subsequently, platinum (Pt) nanoparticles were in situ grown on the Bi₂S_3-x surface, forming a Bi₂S_3-x-Pt Schottky heterojunction and optimizing catalytic activity. These Pt nanoparticles functioned as electron traps, inducing upward energy band bending and establishing a Schottky barrier, thereby bolstering electron-hole pair separation under US stimulation. Furthermore, the catalase (CAT)- and peroxidase (POD)-like activities of the Pt nanoparticles mitigated tumor hypoxia to augment SDT-induced singlet oxygen generation and triggered oxidative stress, respectively. Sono-excited holes were capable of depleting excessive intratumoral glutathione (GSH) and decomposing hydrogen peroxide into O₂, thus alleviating tumor hypoxia and consequently remodeling the tumor microenvironment. To further enhance tumor targeting and dispersity, Bi₂S_3-x-Pt was modified with hyaluronic acid (HA), which specifically binds to CD44 receptors overexpressed on tumor cells. Bi₂S_3-x-Pt@HA, exhibiting these combined functionalities, significantly suppressed tumor proliferation. This study outlines a methodology for enhancing the ROS generation efficiency of inorganic sonosensitizers characterized by narrow bandgaps.