Selenadiazole derivatives as theranostic agents for simultaneous cancer chemo-/radiotherapy by targeting thioredoxin reductase

) into SeD-3 significantly enhanced the anticancer activity of SeDs. The higher lipophilicity endowed SeD-3 with higher cellular internalization ability, resulting in higher cellular uptake and anticancer efficacy. Specifically, the capacity of autofluorescence allowed the use of SeD-3 as a promising theranostic agent to directly monitor the cellular uptake, localization and biodistribution in vitro and in vivo. Interestingly, SeD-3 also significantly enhanced the sensitivity of HeLa cervical cells to X-ray-induced apoptosis by targeting the inhibition of TrxR and promoting intracellular ROS overproduction, which activated the downstream ROS-mediated signaling pathways to regulate cell apoptosis. Furthermore, SeD-3 exhibited satisfactory in vivo antitumor efficacy through the inhibition of tumor proliferation and induction of tumor cell apoptosis, and showed no toxicity to the main organs. Moreover, from the results of hematological analysis, we found that not only inhibiting the tumor growth, treatment of SeD-3 also alleviated the damage of liver, kidney and heart function of nude mice induced by HeLa xenografts. Taken together, this study demonstrates that SeDs could be further developed as an effective and safe theranostic agent for simultaneous cancer chemo-/radiotherapy.