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Singlet Oxygen‐ Versus Nonsinglet Oxygen‐Mediated Mechanisms of Sensitizer Photobleaching and Their Effects on Photodynamic Dosimetry
Author(s) -
Georgakoudi Irene,
Foster Thomas H.
Publication year - 1998
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1998.tb09102.x
Subject(s) - photobleaching , singlet oxygen , photodynamic therapy , chemistry , photochemistry , oxygen , rose bengal , fluorescence , physics , optics , organic chemistry
We report the effects of singlet oxygen ( 1 O 2 ) and non‐ 1 O 2 ‐mediated sensitizer photobleaching on oxygen consumption and dosimetry during photodynamic therapy (PDT) of sensitized multicell tumor spheroids. We develop a theoretical model for the description of non‐ 1 O 2 ‐mediated photobleaching resulting from irreversible reactions of the excited singlet or triplet sensitizer populations with cell substrate. We show that the fluence‐dependent simple exponential decay expression of sensitizer degradation is not consistent with these mechanisms and, therefore, with any reasonable mechanism that we consider, because we have shown previously that 1 O 2 ‐mediated photobleaching cannot be described by a simple exponential with a constant photobleaching coefficient (I. Georgakoudi et al., Photochem. Photobiol . 65 , 135–144, 1997). Analysis of oxygen microelectrode measurements performed at the edge of Nile blue selenium (EtNBSe)‐and protoporphyrin IX (PpIX)‐sensitized spheroids during PDT demonstrates that the former drug photobleaches via a non‐ 1 O 2 ‐mediated mechanism, while the latter is degraded via a 1 O 2 ‐mediated mechanism. Comparisons of the cytotoxic effects of EtNBSe with those of Photofrin® (a drug that is degraded via a 1 O 2 ‐mediated mechanism) indicate that the lower threshold 1 O 2 dose and the higher extinction coefficient and 1 O 2 yield for EtNBSe do not necessarily result in improved photodynamic effects, thus emphasizing the importance of the sensitizer photo‐bleaching mechanism for dosimetry.