An inorganic prodrug, tellurium nanowires with enhanced ROS generation and GSH depletion for selective cancer therapy

• Published in: Chemical science (Cambridge) 2019-08, Vol.1 (29), p.768-775
• Main Authors: Wu, Ying, Guo, Tao, Qiu, Yuan, Lin, Yan, Yao, Yunyan, Lian, Weibin, Lin, Lisen, Song, Jibin, Yang, Huanghao
• Format: Article
• Language: English
• Subjects: Apoptosis; Biocompatibility; Cancer; Chemical compounds; Chemotherapy; Depletion; Drugs; Glutathione; Hydrogen peroxide; Immune system; Nanowires; Serum albumin; Side effects; Tellurium; Tumors
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c9sc01070j

Organic prodrugs have been widely reported to avoid side effects and have been applied for precise tumor therapy in recent years. However, inorganic nano-prodrugs with localized generation of toxic products in the tumor have not been reported. Herein, we report an inorganic nano-prodrug, tellurium nanowires (TeNWs), that generate toxic TeO 6 6− triggered by hydrogen peroxide (H 2 O 2 ) for highly selective cancer chemotherapy. Bovine serum albumin and dextran conjugate coated TeNWs, with a length of ∼82 nm and a width of ∼7 nm, showed high stability in physiological medium. The interaction between TeNWs and intracellular H 2 O 2 produces toxic TeO 6 6− molecules greatly enhanced ROS generation, and the reaction product, verified as TeO 6 6− , would react with glutathione (GSH) and thus decrease intracellular GSH levels, which greatly increases ROS levels in the tumor. Importantly, TeNWs selectively kill cancer cells by caspase-independent autophagic death and apoptosis, as well as exerting an immune response, while not affecting normal cells due to the high H 2 O 2 levels in cancer cells. Moreover, after the sequential reaction with H 2 O 2 and GSH, TeNWs were dissociated into small molecules and could be rapidly and completely removed from the body. Both in vitro and in vivo experiments indicate that TeNWs are a promising inorganic nano-prodrug that exerts good selective therapeutic effects on tumors. A kind of inorganic prodrug, tellurium nanowires with enhanced ROS generation and GSH depletion, was developed for selective cancer therapy with high efficacy.