PHOTODYNAMIC DESTRUCTION OF LYSOSOMES MEDIATED BY NILE BLUE PHOTOSENSITIZERS

Previous studies have established that a number of Nile blue derivativ es arc potent photosensitizers and that they are localized primarily i n the lysosomes. The present study examines whether the lysosome is a main target of the photocytotoxic action mediated by these sensitizers . Chosen for this study were NBS-61 and sat-NBS, which represented, re spectively, derivatives with high and moderate degrees of lysosomal se lectivity. Overall results indicated that both derivatives are very ef fective in mediating a photodestruction of lysosomes. This is indicate d by the light- and drug-dose-dependent losses of acid phosphatase sta ining particles, reduction of hexosaminidase in the lysosome-containin g subcellular fraction, and impairment of the lysosomes to take up and sequester acridine orange. Ultrastructurally, swollen and ruptured ly sosomes were seen as one of the first evidences of cell damage mediate d by these photosensitizers. However, the study also showed that sat-N BS, which is less lysosomal selective, was less effective in mediating lysosomal destruction. Also, the degree of lysosomal destruction medi ated by sat-NBS did not parallel the degree of cytotoxicity generated. This implies that for derivatives that are not exclusively localized in the lysosome, other subcellular sites may also be damaged by the ph otodynamic action and may play a role in the photocytotoxic process.