Photooxidation Responsiveness And Anticancer Activity Of Selenium-containing Polymer Assemblies

Selenium has already been widely used in the construction of reactive oxygen species(ROS)responsive nanomedicine for controlled drug release and improved anticancer efficiency,which could be achieved under the oxidation of endogenous or exogenous ROS.Light have been widely used as a kind of exogenous stimuli for its controllability in time and space.Meanwhile,selenium acts as the active center of various oxidoreductases and plays an important role in maintaining redox balance in human body.Therefore,most of selenium-containing molecules possess certain anticancer activity.At present,most of the researches on selenium-containing nanomedicine mainly focused on its stimuli-responsiveness.However,the potential anticancer activity of selenium-containing polymers has seldom been explored.This thesis mainly focused on the potential antitumor ability of selenium-containing polymers,developed polymers with various topological structures and good biocompatibility,and explored whether light could be used to regulate the anticancer activity of selenium in polymers.This work includes two parts as listed below:(1)The light-induced antitumor activity and mechanism of selenium-containing polymers was revealed.We designed and prepared polymers containing photosensitizer and Se-Se or Se,studied their photooxidation process,and further explored the anticancer mechanism of the photooxidation products.Seleninic acid,the oxidation product of Se-Se and acrylate,the oxidation product of Se under selenoxide-elimination reaction,could react with glutathione,disturb the redox balance in cancer cells and then lead to cell apoptosis.These revealed that selenium-containing polymers could not only be used in controlled release,but also have tunable anticancer ability.(2)The application of selenium-containing polymers in synergistic therapies was realized.The antiangiogenic activity of seleninic acid has already been proved.On the basis of this mechanism,selenium-containing nanomedicine were prepared to combine antiangiogenetic treatment with photodynamic therapy(PDT)and chemotherapy.C-Se bonds could be oxidized and eliminated to form seleninic acid during PDT,led to the disassembly of nanoparticles and the release of loaed chemotherapeutic drugs.Meanwhile,the generated seleninic acid could inhibit angiogenesis.The combination therapy improved the anticancer efficiency of chemotherapy and PDT,which provide a new avenue for the development of selenium-containing polymers in synergistic therapies.