UPTAKE KINETICS AND INTRACELLULAR-LOCALIZATION OF HYPOCRELLIN PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY - A CONFOCAL MICROSCOPY STUDY

Hypocrellins are naturally occurring compounds with photosensitizing p roperties in biological systems. We have prepared synthetic derivative s of hypocrellin B, which have promise as photosensitizers in the clin ical application of photodynamic therapy, The intracellular localizati on and uptake kinetics of hypocrellin B and several selected hypocrell in congeners were determined semiquantitatively by fluorescence confoc al microscopy in monolayer cultures of EMT6/Ed murine tumor cells. Eac h compound had unique uptake kinetics. Although no compound tested to date has demonstrated nuclear labeling, most could be detected in lyso somes, Golgi, endoplasmic reticulum and, to a minor extent, in cellula r membranes. No two compounds gave identical labeling distributions. T he differences are assumed to originate in physicochemical properties characteristic of each compound, which may ultimately impact upon the primary modality of phototoxicity.