Relative contribution of apoptosis and random necrosis in tumour response to photodynamic therapy: effect of the chemical structure of Zn(II)-phthalocyanines

Giulio Jori and Clara Fabris
Department of Biology, University of Padova, via U. Bassi 58/B, 35131 Padova, Italy

jori@civ.bio.unipd.it

Abstract

Zn(II)-phthalocyanine (ZnPc) and its octapentyl (ZnOPPc) and octadecyl (ZnODPc) derivatives were intravenously injected at a dose of 1.46 Ámol/kg to female Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. Pharmacokinetic studies showed that in all cases the maximal concentration of phthalocyanine in the tumour was reached at 24 h post-injection: the efficiency and selectivity of tumour targeting slightly increased 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) at 24 h after photosensitizer administration induced a significant delay of tumour growth, which was largest (ca. 11 days) for ZnPc and smallest (ca. 3.5 days) for ZnODPc. Electron microscopy investigations of irradiated tumour specimens showed that ZnPc caused an early direct damage of malignant cells, largely via processes leading to random necrosis, although a limited contribution of apoptotic pathways was detected. The importance of apoptosis increased upon using ZnOPPc and especially ZnODPc as the photosensitizers possibly owing to a different partitioning in different compartments of cell membranes.