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11 July 2007 New linker design for biomarker-triggered photodynamic molecular beacons
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Photodynamic molecular beacon (PMB) is a novel photodynamic therapy (PDT) concept featuring the precise control of the ability of photosensitizer (PS) to produce singlet oxygen in response to specific cancer-associated biomarkers. It comprises a disease-specific linker, a PS and a singlet oxygen quencher so that the PS's photodynamic toxicity is silenced until the linker interacts with a tumor-associated biomarker. The development of PMB depends on two key factors. The first is the design of a suitable PS-quencher pair to achieve an effective singlet oxygen quenching, minimizing phototoxicity of native PMB in non-targeted (normal) cells. The second is the design of a suitable linker for the choice of target biomarker to achieve a specific photodynamic activation, resulting in selective PDT efficacy in targeted (tumor) cells. These two factors make PMB designs versatile and customizable. In this report, we will focus on the new directions on PMB linker design utilizing two "on-and-off" activation mechanisms. The first one uses a "cleavable" linker that is triggered by fibroblast activation protein or phospholipase. The second one uses an "openable" linker that can hybridize with a tumor-specific mRNA.
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Juan Chen, Pui-Chi Lo, Michael Warren, Klara Stefflova, Jonathan D. Cheng, Brian C. Wilson, and Gang Zheng "New linker design for biomarker-triggered photodynamic molecular beacons", Proc. SPIE 6626, Molecular Imaging, 662603 (11 July 2007);

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