Synthesis And Application Of Light-controlled Prodrugs Based On Phototriggers Of Coumarin And Bezocoumarin Derivatives

The Drug Delivery System (DDS) attracts more and more attention of scientists, lots of research have been committed to this. Drugs can be controlled release by the stimulate of the external environment, such as temperature, pH, magnetic, ion strength and other factors. Among these stimulus, light has its unique advantages. The light-controlled drug delivery system is a process in a non-physical contact, in which the drug can be regulated to release depending on the light conditions. For instance,the drug release only proceed under the irradiation of light, and the quantity of drug release can be regulated by controlling the light intensity and time. Thus, the drug can be released quantitatively in any required spot and time.Nowadays, the development of light controlled prodrug, conjugating the cancer drugs with phototriggers, and then the introduction in the drug delivery system become a popular research topic. These systems not only release the drug on purpose, but also have the advantages of high release efficiency and less by-products et al. In this paper, we designed and synthesized light-controlled prodrugs based on two kinds of phototriggers of coumarin and bezocoumarin derivatives.(1)Due to the advantages of long wavelength absorption, high photo-cleavage efficiency, good stability in dark environment for coumarin phototrigger, we designed to conjugate the anti-cancer drugs chlorambucil with7-aminocoumarin by the esterification to form prodrug. The prodrug was stable under the dark condition and only released the drug under the illumination of light with specific wavelength. And the release of the drug can be regulated quantitatively in any given time and spot by the light conditions, which enhanced the target of the drug and decrease the hurt to normal tissues or cells. Finally we cultured the prodrug with Hela cell and utilized, fluorescence confocal miscroscope to investigate the imaging in the cells, and explore the potential applications in biological area for these kind of prodrugs.(2) Since benzocoumarin compounds have the advantages of long wavelength absorption, large fluorescence quantum yield and Stokes shift value, we designed and synthesized three kinds of benzocoumarin phototrigger derivatives that named A, B, C, respectively. Then these phototriggers were conjugated with the model drug aspirin to form prodrugs. In addition, phototrigger A and B have methylacrylic acid group which can be used to form polymer drug release system.