Intracellular modulation of excited-state dynamics in a chromophore dyad: Differential enhancement of photocytotoxicity targeting cancer cells

Abstract

The photosensitized generation of reactive oxygen species, and particularly of singlet oxygen [O<inf>2</inf>(a1Δ<inf>g</inf>)], is the essence of photodynamic action exploited in photodynamic therapy. The ability to switch singlet oxygen generation on/off would be highly valuable, especially when it is linked to a cancer-related cellular parameter. Building on recent findings related to intersystem crossing efficiency, we designed a dimeric BODIPY dye with reduced symmetry, which is ineffective as a photosensitizer unless it is activated by a reaction with intracellular glutathione (GSH). The reaction alters the properties of both the ground and excited states, consequently enabling the efficient generation of singlet oxygen. Remarkably, the designed photosensitizer can discriminate between different concentrations of GSH in normal and cancer cells and thus remains inefficient as a photosensitizer inside a normal cell while being transformed into a lethal singlet oxygen source in cancer cells. This is the first demonstration of such a difference in the intracellular activity of a photosensitizer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.