Relocalization of cationic porphyrins during photodynamic therapy

When photodynamic therapy is directed against sub-cellular sites that include mitochondria, the anti-apoptotic protein Bcl-2, lysosomes or the endoplasmic reticulum, there is generally an apoptotic response leading to cell death. We previously reported that the targeting of the plasma membrane by photosensitizing agents led to either a marked delay or inhibition of apoptosis, even if other sub-cellular sites were also targeted for photodamage. Preliminary studies indicated that this result was associated with photodamage to caspase-3, a major element of the 'execution' phase of apoptosis. We describe here a mechanism for apoptosis inhibition resulting from localization of photosensitizers from the membrane to the cytosol during irradiation, leading to selective photodamage of procaspases-9, and -3.