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Protoporphyrin IX (PpIX) is a naturally occurring intermediate in the heme biosynthesis pathway. In photodynamic therapy (PDT), PpIX acts as a photosensitizer: after its accumulation in target tissues, exposure to specific wavelengths of light triggers cytotoxic effects through the generation of reactive oxygen species (ROS), primarily singlet oxygen. This mechanism is exploited for selective destruction of pathological cells, such as those found in tumors or inflamed synovial tissue. Exogenous administration of 5-aminolevulinic acid (ALA) or its derivatives leads to increased intracellular synthesis and accumulation of PpIX, especially in rapidly proliferating or metabolically active cells. PDT with PpIX can trigger both apoptotic and necrotic pathways. Abnormal accumulation can cause phototoxic reactions even without therapeutic intent.
Light-induced generation of singlet oxygen/ROS → oxidative cellular damage → cell death via apoptosis and necrosis
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