Title

Localization and Photodynamic Efficacy of Two Cationic Porphyrins Varying in Charge Distribution

Document Type

Article

Publication Date

11-1-2003

Abstract

Two meso-tetraphenylporphyrin derivatives bearing adjacent: 5,10-di[4-(N-trimethylaminophenyl)-15,20-diphenylporphyrin (DADP-a) or opposite: 5,15-di[4-(N-trimethylaminophenyl)-10,20-diphenylporphyrin (DADP-o) cationic-N-(CH3)3+ groups on two of the para-phenyl positions were examined with regard to photodynamic properties as a function of charge distribution. The two adjacent positive charges in the DADP-a structure result in a molecular distortion (asymmetry), likely from electrostatic repulsion. This could be responsible for the unusual interaction of this compound with some solvents and detergent micelles. In contrast, DADP-o is a much more symmetric molecule. In a cellular environment, fluorescence spectra of the two agents were essentially identical. Subcellular localization played a major role in photodynamic efficacy. DADP-a localized in mitochondria, and irradiation of photosensitized cells (640-650 nm) resulted in a rapid loss of the mitochondrial membrane potential (ΔΨm), usually a prelude to apoptotic cell death. In contrast, DADP-o localized in lysosomes, and extensive lysosomal photodamage was observed after irradiation. Both steady-state accumulation levels and absorbance spectra favored DADP-o, but the light dose required for a 90% cell kill was two-fold greater for DADP-o than for DADP-a, at a constant extracellular sensitizer concentration. These data indicate that, on a photons/cell basis, DADP-a was five-fold more efficacious. Fluorescence emission spectra in different solvents and detergents demonstrated a tendency for DADP-a association. We interpret these results to indicate partition of both drugs to membrane loci, with mitochondria being the more lethal site for photodamage.

Publication Source (Journal or Book title)

Photochemistry and Photobiology

First Page

431

Last Page

435

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