Abstract
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.
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Guardiano M, Biolo R, Jori G, Schaffner K. Tetra-n-propylporphycene as tumour localizer:pharmacokinetic and phototherapeutic studies in mice.Cancer Lett 1989,44:1–6
Vogel E, Balci M, Pramod K et al. 2,7,12,17-Tetrapropylporphycene: a counterpart of octaethylporphyrin in the porphyrin series.Angew Chem 1987,99:909–12
Vogel E, Kocher M, Schmickler H, Lex J. Porphycene: a new porphyrin isomer.Angew Chem 1986,98:262–4
Redmond RW, Valduga G, Nonell S et al. The photophysical properties of porphycene incorporated in small unilamellar vesicles.J Photochem Photobiol, B: Biology 1989,3:193–207
Zhou C, Milanesi C, Jori G. An ultrastructural comparative evaluation of tumours photosensitized by porphyrins administered in aqueous solution, bound to liposomes or to lipoproteins.Photochem Photobiol 1988,48:487–92
Reddi E, Lo Castro G, Biolo R, Jori G. Pharmacokinetic studies with Zn(II)-phthalocyanine in tumour-bearing mice.Br J Cancer 1987,56:597–600
Reddi E, Zhou C, Biolo R et al. Zn(II)-phthalocyanine as a photodynamic agent for tumors. I∘Pharmacokinetic properties and phototherapeutic efficiency.Br J Cancer 1990,61:407–11
Selman SH, Kreimer-Birnbaum M, Klaunig JE et al. Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light.Cancer Res 1984,44:1924–7
Star WM, Marijnissen HPA, Van den Berg-Blok AE et al. Destruction of rat mammary tumour and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers.Cancer Res 1986,46:2532–40
Wieman TJ, Fingar VH. Microvascular effects of photodynamic therapy. In: Dougherty TJ (ed)Photodynamic Therapy: Mechanisms. Washington: Proc. SPIE 1065, 1989:11–27
Wieman TJ, Mang TS, Fingar V et al. Effect of photodynamic therapy on blood flow in normal and tumour vessels.Surgery 1988,104:512–7
Henderson BW, Farrell G. Possible implications of vascular damage for tumor cell inactivation in vivo: comparison of different photosensitizers. In: Dougherty TJ (ed)Photodynamic Therapy: Mechanisms. Washington: Proc. SPIE 1065, 1989:2–10
Milanesi C, Zhou C, Biolo R, Jori G. Zn(II)-phthalocyanine as a photodynamic agent for tumors. II. Studies on the mechanism of photosensitized tumor necrosis.Br J Cancer 1990,61:846–50
Barel A, Jori G, Perin A et al. Role of high-, low- and very low-density lipoprotein in the transport and tumor delivery of hematoporphyrin in vivo.Cancer Lett 1986,32:145–50
Kessel D, Thompson P, Saetio K, Nantwi KD. Tumor localization and photosensitization by sulfonated derivatives of tetraphenylporphine.Photochem Photobiol 1987,45:787–90
Slater HR, McKinney L, Packard CJ, Shephard J. Contribution of the receptor pathway to low density lipoprotein catabolism in humans.Arteriosclerosis 1984,4:604–13
Jori G. Pharmacokinetic studies with hematoporphyrin in tumour bearing mice. In: Jori G, Perria CA (eds)Photodynamic Therapy of Tumours and Other Diseases. Padova: Libreria Progetto, 1985:159–66
Aramendia PP. Redmond RW, Nonell S et al. The photophysical properties of porphycenes: potential photodynamic agents.Photochem Photobiol 1986,44:555–9
Hilf R, Smail DB, Murnat RS et al. Hematoporphyrin derivative induced photosensitivity of mitochondrial succinate dehydrogenase and selected cytosolic enzymes of R3230AC mammary adenocarcinomas of rats.Cancer Res 1984,4:1483–8
Jori G, Reddi E, Cozzani I, Tomio L. Controlled targeting of different subcellular sites by porphyrins in tumour bearing mice.Br J Cancer 1986,53:615–21
Svaasand LO. Thermal and optical dosimetry for photoradiation therapy of malignant tumours. In: Andreoni A, Cubeddu R (eds)Porphyrins in Tumour Phototherapy. New York: Plenum Press, 1984:261–79
Rougée M, Bensasson R. Determination des constantes de vitesse de désactivation de l oxygène singulet en présence de biomolécules.CR Acad Sc Paris Série II 1986,302:1223–6
Nekland PA, Zetter BR, Via DP, Voyta CA. In situ labelling of vascular endothelium with fluorescent acetylated low density lipoproteins.Histochem J 1985,17:1309–20
Jori G. In vivo transport and pharmacokinetic behaviour of tumour photosensitizers. In: Bock G, Harnett S (eds)Photosensitizing Compounds: their Chemistry, Biology and Clinical Use, CIBA Foundation Symposium 146. Chichester: Wiley & Sons, 1989:78–94
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Milanesi, C., Biolo, R., Jori, G. et al. Experimental photodynamic therapy with tetrapropyl-porphycene: Ultrastructural studies on the mechanism of tumour photodamage. Laser Med Sci 6, 437–442 (1991). https://doi.org/10.1007/BF02042467
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DOI: https://doi.org/10.1007/BF02042467