Targeted photodynamic therapy agent with a built-in apoptosis sensor for in vivo near-infrared imaging of tumor apoptosis triggered by its photosensitization in situ

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Abstract

Imaging apoptotic cells or tissues after cancer therapy in situ would be a very useful tool for assessing proper treatment conditions and therapeutic outcome. By combining therapeutic and imaging functions, we have designed a multifunctional, membrane-permeable, and cancer-specific agent that triggers and images apoptosis in targeted cells. We chose photodynamic therapy (PDT) as an appropriate cancer treatment modality and caspase 3 as an apoptosis-specific imaging target. This targeted photodynamic therapy agent with a built-in apoptosis sensor (TaBIAS) induces photodamage only to target cells and simultaneously identifies those that are apoptotic by its near-infrared fluorescence. It contains a fluorescent photosensitizer used as an anticancer drug and a cancer-associated folate receptor homing molecule connected to a caspase 3 cleavable peptide linker that has a fluorescence quencher on the opposing site. We demonstrated that PDT-triggered cleavage of the peptide linker by caspase 3, one of the key executioner caspases, results in a detectable increase in fluorescence in folate receptor-overexpressing cancer cells and tumors. The presence of apoptosis was confirmed in vitro by flow cytometry and ex vivo by Apoptag assay, supporting the ability of TaBIAS to specifically induce and image apoptosis in situ. © 2006 BC Decker Inc.

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Stefflova, K., Chen, J., Li, H., & Zheng, G. (2006). Targeted photodynamic therapy agent with a built-in apoptosis sensor for in vivo near-infrared imaging of tumor apoptosis triggered by its photosensitization in situ. Molecular Imaging, 5(4), 520–532. https://doi.org/10.2310/7290.2006.00027

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