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Proceedings Paper

Rational design of a receptor-targeted photodynamic molecular beacon for the multilevel control of singlet oxygen production and PDT activity in cancer cells
Author(s): Juan Chen; Klara Stefflova; Mike Warren; Jiachuan Bu; Brian C. Wilson; Gang Zheng
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Paper Abstract

Photodynamic therapy (PDT) involves the combined action of light, oxygen and a photosensitizer (PS). It offers unique control in the PS's action because the key cytotoxic agent, singlet oxygen (1O2), is only produced in situ upon irradiation. The 1O2 production can be controlled in three levels. The first level involves the judicious use of fiber optics to selectively deliver light to disease tissues. The second level is to exert control over the PS's localization by selectively delivering PS to cancer cells. The third level is to exert control of the PS's ability to generate 1O2 in responding to specific cancer biomarkers. Here, we present two PDT agents based on the latter two levels of 1O2 control. The first PDT agent "PPF" contains a PS (Pyro) and a tumor homing molecule (folate) and a peptide linker. PPF was found to be selectively accumulated in cancer cells via folate receptor (FR) pathway. The second PDT agent "PPMMP7B" is a matrix metalloproteinase-7 (MMP7)-triggered photodynamic molecular beacon (PMB) containing a PS (Pyro), a 1O2 quencher (BHQ3) and a MMP7-cleavable peptide linker. Thus, the 1O2 production of PPMMP7B is highly sequence-specific and its photodynamic cytotoxicity is MMP7-dependent. Since these agents are designed to share functional modules (PS and peptide linker) and common cancer cell model (KB cells overexpress both FR and MMP7), it forms the basis for rational design of receptor-targeted PMB for achieving a multi-level control of 1O2 production in cancer cells, which in term, could provide a much higher level of PDT selectivity.

Paper Details

Date Published: 13 February 2007
PDF: 9 pages
Proc. SPIE 6449, Genetically Engineered and Optical Probes for Biomedical Applications IV, 644906 (13 February 2007); doi: 10.1117/12.699754
Show Author Affiliations
Juan Chen, Ontario Cancer Institute (Canada)
Univ. of Toronto (Canada)
Univ. of Pennsylvania (United States)
Klara Stefflova, Univ. of Pennsylvania (United States)
Mike Warren, Univ. of Pennsylvania (United States)
Jiachuan Bu, Univ. of Pennsylvania (United States)
Brian C. Wilson, Ontario Cancer Institute (Canada)
Univ. of Toronto (Canada)
Gang Zheng, Ontario Cancer Institute (Canada)
Univ. of Toronto (Canada)
Univ. of Pennsylvania (United States)

Published in SPIE Proceedings Vol. 6449:
Genetically Engineered and Optical Probes for Biomedical Applications IV
Samuel Achilefu; Alexander Pavlovich Savitsky; Rebekka M. Wachter; Darryl J. Bornhop; Ramesh Raghavachari, Editor(s)

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