Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy

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• 作者：Andrés M. Durantini ; Lana E. Greene ; Richard Lincoln ; Sol R. Martínez ; Gonzalo Cosa
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：February 3, 2016
• 年：2016
• 卷：138
• 期：4
• 页码：1215-1225
• 全文大小：627K
• ISSN：1520-5126

文摘

Here we show the design, preparation, and characterization of a dormant singlet oxygen (¹O₂) photosensitizer that is activated upon its reaction with reactive oxygen species (ROS), including ¹O₂ itself, in what constitutes an autocatalytic process. The compound is based on a two segment photosensitizer–trap molecule where the photosensitizer segment consists of a Br-substituted boron-dipyrromethene (BODIPY) dye. The trap segment consists of the chromanol ring of α-tocopherol, the most potent naturally occurring lipid soluble antioxidant. Time-resolved absorption, fluorescence, and ¹O₂ phosphorescence studies together with fluorescence and ¹O₂ phosphorescence emission quantum yields collected on Br₂B–PMHC and related bromo and iodo-substituted BODIPY dyes show that the trap segment provides a total of three layers of intramolecular suppression of ¹O₂ production. Oxidation of the trap segment with ROS restores the sensitizing properties of the photosensitizer segment resulting in ～40-fold enhancement in ¹O₂ production. The juxtaposed antioxidant (chromanol) and prooxidant (Br-BODIPY) antagonistic chemical activities of the two-segment compound enable the autocatalytic, and in general ROS-mediated, activation of ¹O₂ sensitization providing a chemical cue for the spatiotemporal control of ¹O₂.The usefulness of this approach to selectively photoactivate the production of singlet oxygen in ROS stressed vs regular cells was successfully tested via the photodynamic inactivation of a ROS stressed Gram negative Escherichia coli strain.