Structure–Photodynamic Effect Relationships of 24 Glycoconjugated Photosensitizers in HeLa Cells

Abstract

The photodynamic effect of the glycoconjugated photosensitizer library containing 16 glycoconjugated 5,10,15,20-tetraphenylporphyrins and 8 glycoconjugated 5,10,15,20-tetraphenylchlorins were examined in HeLa cells, and analyzed by two approaches, namely, physiological properties (cellular uptake and reactive oxygen species (ROS)) and structural features of glycoconjugated photosensitizers. All glycoconjugated photosensitizers showed no cytotoxicity in the dark at a concentration of 5 μM. The photocytotoxicity profiles poorly related to the amount of cellular uptake of the photosensitizers. Photocytotoxicities of the glycoconjugated photosensitizers were inhibited by the ROS inhibitor, sodium azide. The result clearly suggests that singlet oxygen is a dominant species in all cases. The glycoconjugated photosensitizers examined have three structural features, namely, (1) the kind of sugar moieties, (2) the kind of light-absorbing moiety and (3) the substitution position of the sugar moiety. In regard to the sugar moieties, the photosensitizers bearing D-xylose tend to show higher photocytotoxicity than other photosensitizers, while those bearing D-arabinose tend to show lower photocytotoxicity. The photocytotoxicity with respect to the light-absorbing moiety tends to increase in the order of zinc porphyrin<porphyrin<chlorin. The optical density at the Q_I band fairly explained the results. As an effect of the substitution position of the sugar moieties, the photosensitizers bearing sugar moieties at the meta-position of phenyl group showed remarkably high activity compared with para-substituted ones, and the difference could not be explained by the optical density. Confocal laser scanning microscopy revealed that the meta-substituted photosensitizers are not readily deactivated from the excited state in the cellular microenvironment, and this may explain their potent photocytotoxicity.