Ultrastructural damage in photosensitized endothelial cells: dependence on hematoporphyrin delivery pathways.

The subcellular photodamage to endothelial cells in culture, revealed by transmission electron microscopy, was correlated with discrete delivery pathways of hematoporphyrin (HP). Cell detachment from the extracellular matrix, prominent water influx starting at the outer membrane and formation of blebs followed by cell death were the result of photodynamic damage induced by aqueous HP. Serum-bound HP was internalized by endocytosis and accumulated in lysosomal compartments as located after photosensitization. Obstructed lysosomal membranes, degradation of chromatin and swelling of endoplasmic reticulum were revealed in these cells. Red blood cells (RBCs), preincubated with HP, delivered low amounts of the drug to endothelial cells. The photodamage was limited to the nucleus and nucleolus. The role of photosensitizer delivery pathways in cancer cell damage is discussed.