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A Potent Non-Porphyrin Class of Photodynamic Therapeutic Agent: Cellular Localization, Potential and Influence on Hypoxia

Lookup NU author(s): Dr Michael Hall

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Abstract

We have developed a totally new class of nonporphyrin photodynamic therapeutic agents with a specific focus on two lead candidates azadipyrromethene (ADPM)01 and ADPM06. Confocal laser scanning microscopy imaging showed that these compounds are exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the micro-molar range for ADPM01 and nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. Both photosensitisers showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM01 and ADPM06 were highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutics.


Publication metadata

Author(s): Gallagher WM, Allen LT, O'Shea C, Kenna T, Hall M, Gorman A, Killoran J, O'Shea DF

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2005

Volume: 92

Issue: 9

Pages: 1702-1710

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.bjc.6602527

DOI: 10.1038/sj.bjc.6602527


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