title: Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug.
abstract: We designed and synthesized a novel double activatable prodrug system (drug-linker-deactivated photosensitizer), containing a photocleavable aminoacrylate-linker and a deactivated photosensitizer, to achieve the spatiotemporally controlled release of parent drugs using visible light. Three prodrugs of CA-4, SN-38, and coumarin were prepared to demonstrate the activation of deactivated photosensitizer by cellular esterase and the release of parent drugs by visible light (540 nm) via photounclick chemistry. Among these prodrugs, nontoxic coumarin prodrug was used to quantify the release of parent drug in live cells. About 99% coumarin was released from the coumarin prodrug after 24 h of incubation with MCF-7 cells followed by irradiation with low intensity visible light (8 mW/cm(2)) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively as free drugs after the double activation.
authors.affiliation: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States.
authors.forename: Abugafar M L
authors.initials: AM
authors.lastname: Hossion
authors.affiliation: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States ; Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Moses
authors.initials: M
authors.lastname: Bio
authors.affiliation: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States ; Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Gregory
authors.initials: G
authors.lastname: Nkepang
authors.affiliation: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States ; Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Awuah
authors.affiliation: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States ; Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: You
keywords: Prodrug; aminoacrylate; anticancer drug; photosensitizer; photounclick; visible/near IR