Sites of photodamage induced by photodynamic therapy with a chlorin e6 triacetoxymethyl ester (CAME)

The acetoxymethyl ester of chlorin e6 (CAME) was initially designed to be a hydrophobic photosensitizing agent that would be recognized by an endocyti c pathway and initially accumulated in lysosomes. This was expected to lead to hydrolysis of the ester groups, followed key redistribution of the free chlorin to other subcellular sites, In this study, we examined the pattern s of localization of CAME and of subsequent photodamage in murine leukemia L1210 cells, The drug was initially localized at intracellular sites, yield ing a pattern similar to that obtained with a fluorescent probe for acidic intracellular vesicles and endosomes. A brief (30 min) incubation with 10 m u M CAME followed by irradiation led to mitochondrial photodamage and apopt otic cell death. At a higher drug level, or with a longer incubation time, we observed additional photodamage to the plasma membrane and to lysosomes. The higher photodynamic therapy dose led to inhibition of apoptosis, with cell death likely occurring via a necrotic process. Distribution of CAME am ong the components of human plasma was to albumin > high-density lipoprotei n > Bow-density lipoprotein. These results have implications concerning the likely mechanism of CAME accumulation and subcellular distribution.