Coordination Between Selenides And Cisplatin: A Strategy To Realize Anticancer Selectivity Via ROS

The main problem of anticancer drugs in clinical use is side effect. While the drug kills cancer cells, it kills normal cells as well. How to enhance the selectivity of drugs remains a vital issue in drug development. For decades scientists have been trying to develop targeted delivery systems using polymer micelles, vesicles, nanoparticles and other carriers. However, few systems make their way towards tumor specifically due to instability in circulation and the complex microenvironment of tumors. Cisplatin and other platinum based drugs such as carboplatin are potent broad-spectrum anticancer drugs. Cisplatin binds to DNA and inhibits DNA replication. Severe side effects, however, have limited its clinical application.As an essential trace element, selenium participates in the regulation of redox environment in vivo. Studies have shown that selenium compounds are intimately involved in cancer prevention and some of them kill cancer cells by inducing high concentrations of reactive oxygen species(ROS) in vivo. It is greatly anticipated that the combination of metal-based drugs and selenium provides new insights into overcoming the side effects of anticancer drugs.In this thesis, we synthesized selenium-containing amphiphiles and tried to coordinate it with cisplatin. The outcome showed that selenium compounds coordinated with cisplatin successfully and the coordination complex killed cancer cells via different mechanism with cisplatin. Via inducing different concentrations of ROS in cancer cells and normal cells, the complex is well-tolerated in normal cells while retaining high toxicity towards cancer cells. Besides, due to the different mechanism, the complex overcame the resistance of cancer cells towards cisplatin.We hope selenium compounds can get more attention in anticancer fields. Our work can be extended not only to other platinum anticancer drugs, but also to other metal drugs such as ruthenium, titanium and germanium. The coordination between selenium and other metals provides a low-cost and effective resolution of the side effects of traditional chemotherapy drugs.