Selenium Electrophilic Center Responsive to Biological Electron Donors for Efficient Chemotherapy

Designing drugs to intelligently respond to different ratio of biological electron donors/receptors in cancer cells and normal cells is a promising strategy to achieve highly effective and less toxic chemotherapy. Herein by employing metal center to active the selenium-containing electrophilic center drug Ru(phtpy-NO₂)(phenSe)Cl (RuSe) with strongly polarization characteristics are synthesized which can efficiently shuttle electrons from biological electron donors to convert to oxidative stress. The rate of electron transfer at the selenium electrophilic center is 1.81 times higher in cancer cell environments compared to normal cell environments. This results in the selenium electrophilic center being 14.98 times more lethal to cancer cells than to normal cells. Experimental results demonstrate that the transport of electrons process is carried out via selenium radicals intermediate and the rate of electron transport is positively correlated with the polarization properties of the electrophilic center atoms. The selenium electrophilic center transports bioactive electrons to generate a large number of superoxide anions leading to DNA damage and a decrease in mitochondrial membrane potential which further activates the p53 signaling pathway and amplifies the cancer cell-killing effect after transporting bioactive electrons. This work provides a new avenue for the design of efficient and less toxic chemotherapeutic agents.