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Proceedings Paper

The correlation between photosensitizers' membrane localization, membrane-residing targets, and photosensitization efficiency
Author(s): Shany Ytzhak; Shoshana Bernstein; Leslie M. Loew; Benjamin Ehrenberg
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Paper Abstract

Various tetrapyrroles act as photosensitizers by efficiently generating singlet oxygen. Hydrophobic or amphiphilic photosensitizers are taken up by cells and are usually located in various cellular lipid membranes. Passive uptake by a membrane depends on biophysical properties of the membrane, such as its composition, temperature, phase, fluidity, electric potential etc., as well as on the external solution's properties. Although the intrinsic lifetime of singlet oxygen in the membrane phase is 10-30 μs, depending on lipid composition, it escapes much faster out of the membrane into the external or internal aqueous medium, where its lifetime is <3 μs. Any damage that singlet oxygen might inflict to membrane constituents, i.e. proteins or lipids, must thus occur while it is diffusing in the membrane. As a result, photosensitization efficiency depends, among others, on the location of the sensitizer in the membrane. Singlet oxygen can cause oxidative damage to two classes of targets in the membrane: lipids and proteins. Depolarization of the Nernst electric potential on cells' membranes was observed, but it is not clear whether lipid oxidation is a relevant factor leading to abolishing the resting potential of cells' membranes and to their death. We present a study of the effect of membrane lipid composition and the dissipation of the electric potential that is generated across the membrane. We find a clear correlation between the structure and unsaturation of lipids and the leakage of the membrane, which can be caused by their photosensitized oxidization. We demonstrate here that when liposomes are composed of mixtures similar to natural membranes, and photosensitization is being carried out under usual PDT conditions, photodamage to the lipids is not likely to cause enhanced permeability of ions through the membrane, which could be a mechanism that leads to cell death.

Paper Details

Date Published: 13 July 2009
PDF: 10 pages
Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 738029 (13 July 2009); doi: 10.1117/12.827045
Show Author Affiliations
Shany Ytzhak, Bar Ilan Univ. (Israel)
Shoshana Bernstein, Bar Ilan Univ. (Israel)
Leslie M. Loew, Univ. of Connecticut Health Ctr. (United States)
Benjamin Ehrenberg, Bar Ilan Univ. (Israel)

Published in SPIE Proceedings Vol. 7380:
Photodynamic Therapy: Back to the Future
David H. Kessel, Editor(s)

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