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

Organic prodrugs have been widely reported to avoid side effects and were 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 nanowire (TeNW) that generates toxic TeO66- triggered by hydrogen peroxide (H2O2) for highly selective cancer chemotherapy. Bovine serum albumin and dextran conjugate coated TeNW, with a length ~90 nm and width ~7 nm, showed high stability in physiological medium. The interaction between TeNW and intracellular H2O2 produces toxic TeO66 molecules and greatly enhanced ROS generation, which reaction product, verified as TeO66-, would reacte with glutathione (GSH) and thus decreased intracellular GSH levels, which greatly increase ROS levels in the tumor. Importantly, TeNW selectively kills cancer cells by caspase-independent autophagic death and apoptosis, as well as immune responses, while not affecting normal cells due to the high H2O2 levels in cancer cells. Moreover, after sequential reaction with H2O2 and GSH, TeNW was dissociated into small molecule and could be rapidly and completely removed from the body. Both in vitro and in vivo experiments indicate that TeNW is a promising inorganic nano-prodrug that exerts good selective therapeutic effect on tumors.