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Proceedings Paper

New linker design for biomarker-triggered photodynamic molecular beacons
Author(s): Juan Chen; Pui-Chi Lo; Michael Warren; Klara Stefflova; Jonathan D. Cheng; Brian C. Wilson; Gang Zheng
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Paper Abstract

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.

Paper Details

Date Published: 11 July 2007
PDF: 8 pages
Proc. SPIE 6626, Molecular Imaging, 662603 (11 July 2007); doi: 10.1117/12.728395
Show Author Affiliations
Juan Chen, Univ. of Toronto (Canada)
Ontario Cancer Institute (Canada)
Univ. of Pennsylvania (United States)
Pui-Chi Lo, Univ. of Toronto (Canada)
Michael Warren, Univ. of Pennsylvania (United States)
Klara Stefflova, Univ. of Pennsylvania (United States)
Jonathan D. Cheng, Fox Chase Cancer Ctr. (United States)
Brian C. Wilson, Univ. of Toronto (Canada)
Ontario Cancer Institute (Canada)
Gang Zheng, Univ. of Toronto (Canada)
Ontario Cancer Institute (Canada)
Univ. of Pennsylvania (United States)

Published in SPIE Proceedings Vol. 6626:
Molecular Imaging
Kai Licha; Vasilis Ntziachristos, Editor(s)

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