Relative contributions of apoptosis and random necrosis in tumour response to photodynamic therapy: effect of the chemical structure of Zn(II)-phthalocyanines
✍ Scribed by Giulio Jori; Clara Fabris
- Publisher
- Elsevier Science
- Year
- 1998
- Tongue
- English
- Weight
- 448 KB
- Volume
- 43
- Category
- Article
- ISSN
- 1011-1344
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✦ Synopsis
Zn(II)-phthalocyanine (ZnPc) and its octapentyl (ZnOPPc) and octadecyl (ZnODPc) derivatives have been intravenously injected at a dose of 1.46 ixmol/kg into female Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. Pharmacokinetic studies show that in all cases the maximal concentration of phthalocyanine in the tumour is reached at 24 h post-injection: the efficiency and selectivity of tumour targeting slightly increase upon increasing the length of the alkyl substituents. Irradiation of the neoplastic lesion (620-700 nm light, 180 mW/cm 2, 300 J/cm 2) 24 h after photosensitizer administration induces a significant delay of tumour growth, which was largest ( ~ 11 days) for ZnPc and smallest ( ~ 3.5 days) for ZnODPc. Electron microscopy investigations of irradiated tumour specimens show that ZnPc causes an early direct damage of malignant cells, largely via processes leading to random necrotic pathways, although a limited contribution of apoptotic pathways is detected. The importance of this increased upon using ZnOPPc and especially ZnODPc as the photosensitizers, possibly due to a different partitioning in different compartments of cell membranes.