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“Competitive Quenching”: A Mechanism by Which Perihydroxylated Perylenequinone Photosensitizers Can Prevent Adverse Phototoxic Damage Caused by Verteporfin During Photodynamic Therapy
Author(s) -
Lavie Gad,
Barliya Tilda,
Mandel Mathilda,
Blank Michael,
Ron Yonina,
Orenstein Arie,
Livnat Tami,
Friedman Noga,
Weiner Lev,
Sheves Mordechai,
Weinberger Dov
Publication year - 2007
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.1751-1097.2007.00171.x
Subject(s) - phototoxicity , photodynamic therapy , hypericin , singlet oxygen , verteporfin , photochemistry , chemistry , quenching (fluorescence) , retinal , biophysics , photothermal therapy , fluorescence , pharmacology , oxygen , nanotechnology , biochemistry , in vitro , materials science , medicine , organic chemistry , optics , physics , choroidal neovascularization , biology
Incorporation of photodynamic therapy into clinical practice for induction of vascular photo‐occlusion highlights the need to prevent adverse phototoxicity to sensitive juxtaposed tissues, particularly in the retina. We developed a system termed “competitive quenching” to prevent adverse phototoxic damage. It involves differential compartmentalization of a photoactivator to the intravascular compartment for photoexcitation and delivery of phototoxicity to targeted vessels. A different photodynamic agent is partitioned to the extravascular retinal space to quench reactive oxygen species generated by photosensitization, thereby protecting the adjacent retinal tissues from adverse phototoxicity. The absorption spectra of quenchers must span wavelengths that are shorter and excluded from the spectral range of photoexcitation light to prevent photoactivation of the quencher. Perihydroxylated perylenequinones were found to be suitable to function as “competitive quenchers” with the prototype hypericin identified as a potent quencher. Here we examined the mechanisms operative in competitive quenching and suggest that hypericin forms a complex with verteporfin, thereby quenching singlet oxygen formation. Furthermore, we show that hypericin, with six phenolic hydroxyls, protects retinal and endothelial hybridoma cells from phototoxicity more effectively than the dimethyl tetrahydroxy helianthrone structural analog with only four such phenolic hydroxyls. The findings suggest that hydroxyl numbers contribute to the efficacy of competitive quenching.