Promotion of PDT efficacy by low-dose lysosomal photodamage

There have been literature reports indicating that protocols involving two photosensitizing agents, in animal tumor models, can yield a synergistic result, i.e., more photokilling than can be obtained with either sensitizer alone at the same light dose. We have independently obtained similar results in a cell-culture system that permits a more detailed study of mechanisms involved. Using any of three agents that localize in lysosomes, we were able to show that low-dose lysosomal photodamage could substantially promote photokilling by benzoporphyrin derivative, an agent that primarily targets mitochondria. This effect was abolished by knockdowns of either of two genes normally associated with autophagy: ATG5 and ATG7. A mechanism that can account for these results is proposed.