Self-assembly And Anticancer Activity Of Selenium-containing Compounds

Selenium is an essential trace element of human body with good biocompatibility.Selenium-containing compounds can sensitively respond to stimulus,such as redox,light,and radiation,resulting in the change of hydrophilicity.Therefore,selenium-containing polymers have been widely applied in the construction of responsive nanomedicine carriers for anticancer drug delivery and controlled release.Moreover,selenium may possess anticancer activity on its own because it has the ability of regulating redox balance in human body as the center of various enzymes.The thesis studies the anticancer activity and the mechanism of selenium-containing compounds,develops a series of selenium-containg self-assemblies with concise structures.The assembies show good anticancer activity and low side effects,thus exhibiting great potential for clinical cancer treatment.The work includes three main topics as follows:1)Selenium-platinum coordination assemblies with concise structures were developed,which may fill in the blank of clinical selenium-containing anticancer drug.Selenium-containing molecules were designed and coordinated with platinum to form assembly nanomedicine.The assemblies exhibited good anticancer activity and low side effects with a mechanism of inducing high levels of reactive oxygen species(ROS)to kill cancer cells.2)The interactions between selenium and metals other than platinum were explored.Selenium-containing compounds were found to simultaneously reduce and stabilize gold(?),and prepare uniform 2 nm gold nanoparticles in one step.The selenium prepared gold nanoparticles induced cancer cell apoptosis by regulating intracellular ROS concentration,thus inhibiting tumor growth.In addition,selenium was found to coordinate with metals such as nickle,copper,and zinc,resulting in coordination complexes with anticancer activity.This work shed light on a platform of anticancer drugs based on selenium-containing compounds.3)The cancer immunoactivity of seleninic acid was revealed.On the basis of this mechanism,diselenide assemblies were developed to combine cancer immunotherapy with radiotherapy and chemotherapy.Diselenides could be cleaved by ?-radiation to form seleninic acids,which suppressed the expression of human leukocyte antigen E(HLA-E)in cancer cells,and then activated the immunoactivity of nature killer(NK)cells.Combination between cancer immunotherapy and radiotherapy was consequently achieved.Moreover,co-assembly between diselenides with chemotherapeutic drugs further introduced chemotherapy into the combination strategy.The combination therapy improved the antitumor efficacy of immunotherapy while maintaining the low side effects,which opened a new avenue for selenium-containing compounds in cancer immunotherapy.