Secondary Dark Reactions Following Photodynamic Treatment are More Damaging Than Previously Thought

Photodynamic treatment is often thought to produce reactive oxygen species (ROS) that directly induce killing; the nomenclature and phrases revolve around such notions of light-dependency. Few studies reference the possible existence of oxidation products formed in secondary reactions, which bear cytotoxicity competitive to their ROS precursors. Here, we highlight the paper by Girotti and Korytowski in this issue of Photochemistry and Photobiology, which does just that. In this paper, they report on cholesterol hydroperoxides, which are formed after photosensitized oxidation and yield cytotoxic mixtures in dark reactions after the light's turned off. Some of the hydroperoxides are transported by protein carriers and damage tissue outside their site of origin. A similar dark cytotoxicity may be anticipated for biological peroxides from in vivo photodynamic therapy.