Molecular biological mechanisms in photodynamic therapy

Abstract

Cellular and molecular photodamage mechanisms are initiated by light-activation of a photosensitizer following its accumulation in cellular targets. While lethal doses of photodynamic therapy (PDT) eliminate vessels and cells, sublethal effects occur, e.g., during fluorescence diagnosis (FD). Accordingly, the events subsequent photoactivation lead to different cellular endpoints being primarily growth stimulation, damage repair, autophagy, apoptosis, and necrosis. Activation of survival pathways seems to be not only involved in growth stimulation, but also in PDT damage transmission. Sublethal PDT results from activation of cellular damage protection and adaptive mechanisms, and can modulate signaling pathways and immune reactions. Autophagy may serve to rescue cells or lead to cell death under special conditions. Lethal PDT activates stress response, e.g., via mitochondria or ER, inducing apoptosis. If the damage is too severe, the cellular energy level low or the plasma membrane leaky, cells will die by necrosis.