S. Muller et al., TETRAAMIDO-SUBSTITUTED 2,3-NAPHTHALOCYANINE ZINC(II) COMPLEXES AS PHOTOTHERAPEUTIC AGENTS - SYNTHESIS, COMPARATIVE PHOTOCHEMICAL AND PHOTOBIOLOGICAL STUDIES, Journal of photochemistry and photobiology.B, Biology, 35(3), 1996, pp. 167-174
The aim of this study is to report the synthesis and photochemical and
phototherapeutic activities of tetraamido-substituted 2,3-naphthalocy
anine zinc(II) complexes (ZnNcs 5-8). Four naphthalocyanine complexes,
tetrabenzamido- (ZnNc 5), tetramethoxybenzamido- (ZnNc 6), tetrahexyl
amido- (ZnNc 7) and tetradodecylamido- (ZnNc 8) naphthalocyanine zinc
complexes absorbing at around 770 nm were synthesized. The dye-sensiti
zed photo-oxidation of 1,3-diphenylisobenzofuran via O-1(2) was studie
d in more detail in order to compare the quantum yields of these diffe
rent sensitizers. Pharmacokinetic and photodynamic therapy studies of
Lewis lung carcinoma in mice were carried out after administration of
liposome incorporated ZnNcs 5-8. The phototherapeutic efficiency was e
valuated by changes in the mean tumour diameter with time, regrowth de
lay (days), average survival time (days) and electron microscopy obser
vations. According to all assessment criteria used, the most promising
photosensitizer seems to be tetrabenzamido-substituted ZnNc 5. We sug
gest that mainly structural properties are the reason for the better r
esults observed. The morphological analysis confirms the mechanism of
photonecrosis, which was observed in our previous work with unsubstitu
ted and substituted ZnNcs 1-4. Direct photodamage to the membrane, mit
ochondria and rough endoplasmic reticulum in the neoplastic cells and
delayed photodestruction of the endothelial cells surrounding the tumo
ur tissue were detected. Also, changes in lysosomes were observed. The
data presented through different parameters are compared with such ob
tained for other photodynamic therapy sensitizers.