LYSOSOMES, A KEY TARGET OF HYDROPHOBIC PHOTOSENSITIZERS PROPOSED FOR PHOTOCHEMOTHERAPEUTIC APPLICATIONS

Despite their important biological activity, lysosomes have been gener ally neglected as important primary targets of photosensitizers, becau se they are not easily accessible for experiments. This paper reviews factors favoring the localization of photosensitizers in lysosomes and the various experimental approaches which have been used so far for t he characterization of the lysosomal staining by various photosensitiz ing dyes, including porphyrins, chlorins and phenoxazines. The experim ental difficulties observed in combining several in vitro techniques f or the unambiguous demonstration of lysosomal targeting are examined. New data on tetraphenylporphine derivatives and a pyropheophorbide, as well as previous data on photofrin II, are presented to illustrate th e advantages and possibilities of microspectrofluorometry in the study of photosensitizer localization in single living cells. Both spectral and topographic information available from areas smaller than 1 mum2 make it possible to characterize fairly specific sites of localization through the use of specific and vital fluorescent probes of lysosomes , such as Lucifer Yellow. It is also shown by microspectrofluorometry on single living cells that the chronology of the photosensitized reac tions induced by specific or unspecific lysosomal photosensitizers can be easily followed. The photosensitized lipofuscin formation observed at the plasma membrane level with the lysosomotropic tetraphenylporph ine supports the contention that it is very rare to find a truly speci fic lysosomal photosensitizer.