Zn(II)-phthalocyanine as a photodynamic agent for tumours. II. Studies on the mechanism of photosensitised tumour necrosis.
The mechanism of tumour necrosis photosensitised by liposome-delivered Zn(II) phthalocyanine (Zn-Pc) has been studied in mice bearing a transplanted MS-2 fibrosarcoma. Ultrastructural analyses of tumour specimens obtained at different times after red light-irradiation (300 J cm-2, dose-rate 180 mW cm-2) indicate an early (3 h) photodamage of malignant cells especially at the level of the mitochondria and rough endoplasmic reticulum. The cellular damage becomes more evident between 6 h and 15 h after photodynamic therapy. On the other hand, the capillaries supplying the tumour tissue are modified at a much slower rate and appear to be severely damaged only after 15 h from irradiation, when the whole tissue becomes necrotic. Occasionally, mildly damaged capillaries are observed even at 72 h after irradiation. These findings support the hypothesis that low density lipoproteins (LDL) play a major role in the delivery of Zn-Pc to the tumour tissue; the photosensitiser is released specifically to malignant cells as a consequence of a receptor-mediated endocytosis of LDL.
Milanesi
C
C
Department of Biology, University of Padova, Italy.
Zhou
C
C
Biolo
R
R
Jori
G
G
D000818:Animals; D005354:Fibrosarcoma / Q000188:drug therapy / Q000648:ultrastructure; D007211:Indoles / Q000627:therapeutic use*; D054833:Isoindoles; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009336:Necrosis; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured; D017967:Zinc Compounds
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine