Sulfur Vacancy‐Enriched Cu ₄ SnS _4−x Nanosheets Enable Synergistic Cuproptosis, Photothermoelectric Catalytic and Immunotherapy

Abstract

ABSTRACT Photothermoelectric catalytic therapy (PTECT) faces challenges like restricted thermoelectric activity and tumor recurrence. In this study, we introduce a defect engineering strategy to synthesize sulfur vacancies (S v ) enriched Cu 4 SnS 4−x nanosheets with promising thermoelectric properties, followed by loading small‐molecule inhibitor NLG919. Spherical aberration corrected transmission electron microscopy and X‐ray absorption fine structure reveal the fine structural characteristics of S v , which make the nanosheets possess an ultra‐high photothermal conversion efficiency of 64.7% under 808 nm laser irradiation. This generates a localized temperature gradient that induces an internal electric field, which enhances carrier separation, boosts peroxidase‐ and catalase‐like activities, and produces substantial amounts of reactive oxygen species (ROS), enabling cooperative PTECT and multi‐enzymatic catalytic therapy. Density functional theory calculations show that S v reduces the thermal conductivity, thus enhancing the figure of merit value and the PTECT effect. Accumulation of Cu ions, ROS, and heat triggers cuproptosis, mitochondrial apoptosis, and endoplasmic reticulum‐based immunogenic cell death. The released NLG919 disrupts the IDO‐induced Trp/Kyn metabolic pathway, reversing the tumor immune suppressive microenvironment. This integrated approach achieves high efficiency (96%) and long‐term anticancer efficacy. These findings may provide valuable insights for advancing thermoelectric materials in tumor therapy.