Self‐Doped Cu _2+x Zn _1‐x SnSe ₄ Nanosheets for Enhanced Thermoelectric Catalytic‐Ferroptotic Therapy

Abstract

Abstract Thermoelectric technology, a rapidly advancing field in medical therapy, encounters challenges in achieving efficient thermal and electrical transport properties within the limited thermal range compatible with biological systems. This study presents a high‐performance thermoelectric catalytic therapy (TECT) utilizing Cu self‐doped Cu 2+x Zn 1‐x SnSe 4 nanosheets synthesized with non‐stoichiometric ratios modified with DSPE‐mPEG 2000 (n‐CZTSe@PEG NSs). Under 808 nm laser irradiation, n‐CZTSe@PEG NSs demonstrate an impressive photothermal conversion efficiency of 47.62%, rapidly establishing a significant local temperature gradient. This increase in temperature initiates thermoelectric catalysis (TEC), effectively generating reactive oxygen species (ROS) that are toxic to cancer cells. The thermoelectric figure of merit ZT of n‐CZTSe@PEG NSs at room temperature is observed to be 45.45% higher than that of pure phase CZTSe. Experimental results, supported by density functional theory calculations, reveal that lattice disorder and the presence of highly degenerate electronic bands at the band edges decouple thermal and electrical transport, enhancing the TEC effect. The additional copper ions at zinc sites increase carrier concentration, hole conductivity, and peroxidase‐like activity, thereby enhancing ROS production, depleting glutathione, accelerating lipid peroxidation, and inhibiting glutathione peroxidase 4, ultimately inducing ferroptosis in cancer cells. Consequently, a synergistic TECT and ferroptosis effect is achieved, resulting in significant anti‐cancer efficacy.