Relative contributions of apoptosis and random necrosis in tumour response to photodynamic therapy: effect of the chemical structure of Zn(II)-phthalocyanines.
Zn(II)-phthalocyanines (ZnPc) and its octapentyl (ZnOPPc) and octadecyl (ZnODPc) derivatives have been intravenously injected at a dose of 1.46 mumol/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/cm2, 300 J/cm2) 24 h after photosensitizer administration induces a significant delay of tumour growth, which was largest (approximately 11 days) for ZnPc and smallest (approximately 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.
Jori
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Department of Biology, University of Padua, Italy. jori@civ.bio.unipd.it
Fabris
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D000818:Animals; D017209:Apoptosis; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology*; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054833:Isoindoles; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009336:Necrosis; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017967:Zinc Compounds
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C114656:zinc(II)-octadecyl-phthalocyanine; C061188:zinc 1,4,8,11,15,18,22,25-octa-n-butoxyphthalocyanine; C052159:Zn(II)-phthalocyanine