Urchin‐Like Sulfate Radical Nano‐Generator Based on MoS2/Bi2S3 Heterostructure for Enhanced Anticancer Therapy

Abstract Sulfate radicals (SO 4 •− ), characterized by their superior oxidative potential (2.5–3.1 V) and extended half‐life (30–40 µs), hold promise for overcoming the limitations of conventional reactive oxygen species (ROS) in cancer therapy. However, current SO 4 •− generation strategies rely on exogenous persulfate (PMS), limiting their therapeutic efficiency and clinical applicability. Herein, an urchin‐like BiS 2 /MoS 2 ‐NH 2 (BMSN) is reported that enables self‐sufficient SO 4 •− generation under near‐infrared (NIR) irradiation without PMS. The heterostructure design facilitates efficient charge separation and broadens light absorption, while the urchin‐like morphology enhances photothermal conversion (33.6% efficiency) and catalytic activity. Upon NIR exposure, photogenerated holes and hydroxyl radicals (·OH) oxidize intrinsic S 2− ions to form SO 4 •− via a cascade reaction (S 2− → SO 3 2− → HSO 5 − → SO 4 •− ), as validated by ESR and LC‐MS. Surface modification with cationic polymers enables mitochondria‐targeted delivery, inducing mitochondrial membrane depolarization and apoptosis through localized SO 4 •− ‐mediated oxidative damage. In vitro studies demonstrated >50% cancer cell inhibition at 40 µg mL −1 BMSN, while in vivo experiments showed significant tumor suppression in 4T1 xenograft models with negligible systemic toxicity. This work pioneers a PMS‐free sulfate radical therapy, integrating photothermal amplification and catalytic nanomedicine, and establishes a paradigm for designing non‐oxygen‐centered radical‐based anticancer strategies.