Experimental photodynamic therapy with tetrapropyl-porphycene: Ultrastructural studies on the mechanism of tumour photodamage

Red light irradiation of a transplanted MS-2 fibrosarcoma in mice at 24 h after injection of liposome-zbound tetra-n-propyl-porphycene (TPP, 2mg kg^–1 b.w.) caused an efficient tumour necrosis. Electron microscopy analysis of tumour specimens taken at different times after the phototherapeutic treatment showed the development of direct damage of malignant cells between 3 and 6 h; the earliest detectable alterations occurred at the level of mitochondria. The endocellular damage gradually progressed with extensive vacuolization of the cytoplasm and, at later stages, formation of pyknotic nuclei. On the other hand, the vascular system of the tumour appeared to be well preserved up to about 9 h, when several endothelial alterations were detected. The damage of the tumour tissue was essentially complete 24 h after the phototreatment. The pattern of tumour modification is consistent with a preferential transport and tumour release of the liposome-bound TPP by low-density lipoproteins.