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Proceedings Paper

Interaction of phthalocyanine photodynamic treatment with ionophores and lysosomotrophic agents
Author(s): Nancy L. Oleinick; Marie E. Varnes; Marian E. Clay; Harry J. Menegay
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Paper Abstract

Phthalocyanines are receiving increasing attention as second-generation sensitizers for photodynamic therapy (PDT). This paper discusses some of the investigations into the mechanism of the phototoxic responses of phthalocyanine-sensitized PDT exploiting the interaction of PDT with other metabolic modulators. Among the agents which interact strongly with PDT is the K+/H+ ionophore nigericin. Under the conditions studied with chloroaluminum phthalocyanine (AlPcCl), the Na+/H+ ionophore monensin, the Ca++ ionophore A23187, and the lysosomotrophic agent chloroquine, but not the K+ ionophore valinomycin, also potentiate photodynamic cell killing. None of the latter compounds interact with PDT as strongly as does nigericin. Both nigericin and monensin partially inhibit cellular respiration; however, KCN, which inhibits respiration completely, is less effective in potentiating PDT damage than is nigericin. Nigericin treatment alone does not deplete glutathione; however, the GSH level decreases after treatment of cells with PDT and nigericin. The potentiation of the PDT response is much greater at an extracellular pH (pHe) of 6.70 than at pHe 7.30. When nigericin is present at pHe 6.70, the intracellular pH (pHi) is equilibrated with pHe. None of the other ionophores tested was able to cause the acidification of the intracellular milieu as did nigericin. The evidence to date suggests that the lowering of pHi is an important component of the mechanism by which nigericin potentiates PDT.

Paper Details

Date Published: 1 June 1991
PDF: 9 pages
Proc. SPIE 1426, Optical Methods for Tumor Treatment and Early Diagnosis: Mechanisms and Techniques, (1 June 1991); doi: 10.1117/12.44063
Show Author Affiliations
Nancy L. Oleinick, Case Western Reserve Univ. School of Medicine (United States)
Marie E. Varnes, Case Western Reserve Univ. School of Medicine (United States)
Marian E. Clay, Case Western Reserve Univ. School of Medicine (United States)
Harry J. Menegay, Case Western Reserve Univ. School of Medicine (United States)


Published in SPIE Proceedings Vol. 1426:
Optical Methods for Tumor Treatment and Early Diagnosis: Mechanisms and Techniques
Thomas J. Dougherty, Editor(s)

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