The in vitro photodynamic inactivation ofherpes simplex virus (HSV-1), an enveloped virus with a membranous coat, was studied using the decaalky sapphyrin 2. This new sensitizer, an unusual 22 icelectron "expanded porphyrin" with an absorption maximum at roughly 680 nm, generates singlet oxygen in roughly 25% quantum yield in its non-aggregated monomeric form and is very efficient for the photo-inactivation of HSV- 1 . It is as active as dihematoporphyrin derivative (DHE) on a per macrocycle basis and, because of light absorption by oxyhemoglobin, considerably more so in blood on a per mcident light intensity basis. Supporting fluorescence studies indicate that compound 2 has a high affinity for nonpolar environments, where it exists in its most active monomeric form, suggesting a mechanism of action that depends both on selective localization in the HSV- 1 viral membrane and accompanying efficient singlet oxygen production. In preliminary experiments with cell-free HIV-1 (also an enveloped virus), it was found that compound 2 effects a ca. 50% photo-killing with little dark toxicity at 4 jiM concentration and an essentially complete photo-eradication at 16 jiM concentration, as judged by standard reverse transcriptase assay. At this latter concentration, however, the light-induced viral inactivation is accompanied by considerable dark toxicity, which, on the basis of control experiments with uninfected cells, is ascribed to a high sensitivity of the H9 cell line employed and not to an overall, or inherent, cytotoxicity of the sapphyrin nucleus.

Date Published: 1 July 1990
PDF: 13 pages
Proc. SPIE 1203, Photodynamic Therapy: Mechanisms II, (1 July 1990);

Published in SPIE Proceedings Vol. 1203:
Photodynamic Therapy: Mechanisms II
Thomas J. Dougherty, Editor(s)