To determine factors that govern the uptake preference of photosensitizers in cellular organelles of human
adenocarcinoma cells, diarginyl-dialkoxy- and diarginyl-dimethoxyphenylporphyrins (TPPs) and two of their
corresponding indium(III) complexes were synthesized, characterized and incubated in androgen-sensitive human
prostate adenocarcinoma cells LNCaP. The porphyrins revealed properties that are of importance for phototherapy.
They are water-soluble, have their fourth Q-band absorbing at ≈ 650 nm, are taken up in relatively high concentrations in
LNCaP cells, and are phototoxic. Colocalization and phototoxicity studies revealed that all porphyrins localized
preferentially to the lysosomes and invoked cell death when excited with 650 nm light. Compared to the corresponding
methoxy-substituted TPPs, the diargininyl-dialkoxy-substituted porphyrins localized to a small extent in the
mitochondria. The corresponding In(III) chloride complexes that are slightly less water-soluble were also taken up in the
lysosomes of LnCaP cells. When the TPPs were compared to a pheophorbide derivative recently synthesized in our
laboratory, it was determined that the TPPs have a preference for lysosomal localization, whereas the pheophorbide
derivative co-localized to the mitochondria. Phototoxicity studies revealed that the longer chain dialkoxyTPPs were
more effective in cell killing and induced greater morphological changes typical of apoptotic cell death than the shorter
chain methoxy substituted porphyrins. The In(III) complexes seemed to be the most phototoxic. These results highlight
that the type, nature, and substitution pattern of the chromophore modulate the extent of apoptotic cell death and
influence cellular targeting.