Photodynamic effect of deuteroporphyrin IX derivatives on isolated nerve cell

Abstract

Deuteroporphyrin IX derivatives are prospective PDT porphyrin photosensitizers (PS). The photodynamic effects of 6 new amphiphilic deuteroporphyrin derivatives with different hydrophobicity, as well as effects of known photosensitizers Photoheme and Photosens (used for comparison) on the firing of isolated crayfish mechanoreceptor neuron have been studied. After 30 min photosensitization, neurons were irradiated with He-Ne laser (632,8 nm, 0,3 W/cm2), and changes in neuron firing frequency were recorded. It has been shown that neuron firing is very sensitive to photodynamic impact and can serve as a sensitive indicator of cell photodamage. The comparison of dependencies of neuron lifetime on photosensitizer concentrations has provided comparison of their photodynamic efficiencies. The studied deuteroporphyrin IX derivatives have been found to be very potent PS. They induced irreversible firing abolition at pikomolar concentrations while Photoheme and Photosens were effective in the nanomolar range. The most effective PS were 4-(1-methyl-3-hydroxybutyl)- and 4-(1-methyl-2-acetyl-3-oxobutyl)-deuteroporphyrins. High photodynamic efficiencies of deuteroporphyrin derivatives were related to a weak dependence of photodynamic effect on sensitizer concentration, indicating that an initiation of several (3-5) chains of secondary processes such as free radical membrane damage by absorption of photon by photosensitizer molecule could take place. The main photosensitizer feature determining its intracellular localization and photodynamic efficiency has been amphiphilicity.