Schottky barrier in pea-like Au@Bi2S3 nanoreactor enabling efficient photodynamic therapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a leading cause of tumor-related mortality globally, demands innovative therapeutic strategies to overcome limitations of conventional treatments. Photodynamic therapy (PDT), reliant on reactive oxygen species (ROS) generation, has emerged as a promising therapeutic strategy for neoplastic diseases. But it is constrained by inefficient charge separation in traditional photosensitizers. Here, we engineered a pea-like Au@Bi₂S₃ nanoreactors by anchoring gold nanoparticles onto Bi₂S₃ surfaces to establish a Schottky junction with interfacial Au-S covalent bonds, which suppresses electron-hole recombination and amplifies ROS production. Under light irradiation, Au@Bi₂S₃ exhibited remarkable inhibitory efficacy against HepG-2 cells, producing twice the ROS yield of Bi₂S₃. Transcriptomic analysis via RNA sequencing identified activation of the Hippo/Yap signaling pathway, which orchestrated endoplasmic reticulum stress and autophagic flux in malignant cells, ultimately driving apoptotic elimination of HepG-2 populations. These findings delineate a mechanistic paradigm wherein Schottky junction engineering potentiates ROS-mediated cytotoxicity, thereby advancing precise photodynamic interventions for HCC management.