Nano-flower-stick composite structure S-scheme Au/MoS2/Bi2S3 heterojunction with multiple enzyme-like activity for efficient tumor photothermal and photodynamic combination therapy

• An S-scheme Au/MoS 2 /Bi 2 S 3 heterojunction with multi-enzyme activities was innovatively designed for enhanced photothermal and photodynamic tumor therapy. • This novel nano-catalyst effectively overcame the tumor microenvironment’s resistance by synergistically generating reactive oxygen species and depleting glutathione through PTT/PDT. • Photoactivated Au/MoS 2 /Bi 2 S 3 significantly suppressed tumor growth and promoted apoptosis, offering superior efficacy and excellent biological safety in both in vitro and in vivo models. Nano-catalytic therapy mediated by reactive oxygen species (ROS) is a highly promising tumor treatment strategy. However, the unique physiological and biochemical characteristics of tumor microenvironment, such as hypoxia and overexpression of antioxidants and glutathione, limit the production of ROS and their oxidation capacity within the tumor. In this study, an S-scheme heterojunction (Au/MoS 2 /Bi 2 S 3 ) with multiple enzyme activities was constructed to achieve significant anti-tumor effects through photothermal/photodynamic combination therapy (PTT/PDT). Under near infra-red irradiation, Au/MoS 2 /Bi 2 S 3 heterojunction not only provided high fever for PTT but also generated singlet oxygen for PDT. In addition, the Au/MoS 2 /Bi 2 S 3 heterojunction also could generate H 2 O 2 in-situ (Glucose oxidase-like activity), meanwhile simultaneously complete the decomposition of endogenous H 2 O 2 (Peroxidase-like and Catalase-like activity) and depletion of glutathione (Glutathione-peroxidase-like activity) through the conversion between Mo 4+ and Mo 6+ , further enhancing the generation of ROS. In vitro and in vivo studies demonstrated that the photoactivated Au/MoS 2 /Bi 2 S 3 heterojunction, with its multiple enzyme-like activities, could effectively achieve tumor regression within the observation period while also exhibiting high biological safety. This study provided a new perspective for tumor therapy based on nano-catalytic method.