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Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions

Photodynamic therapy (PDT) is used to treat malignancies and precancerous lesions. Near-infrared light delivered by lasers was thought for a while to be the most appropriate option to activate photosensitizers, mostly porphyrins, in the depth of the diseased tissues. More recently, however, several...

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Autores principales: Doix, Bastien, Bastien, Estelle, Rambaud, Alix, Pinto, Adán, Louis, Caroline, Grégoire, Vincent, Riant, Olivier, Feron, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160539/
https://www.ncbi.nlm.nih.gov/pubmed/30298119
http://dx.doi.org/10.3389/fonc.2018.00393
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author Doix, Bastien
Bastien, Estelle
Rambaud, Alix
Pinto, Adán
Louis, Caroline
Grégoire, Vincent
Riant, Olivier
Feron, Olivier
author_facet Doix, Bastien
Bastien, Estelle
Rambaud, Alix
Pinto, Adán
Louis, Caroline
Grégoire, Vincent
Riant, Olivier
Feron, Olivier
author_sort Doix, Bastien
collection PubMed
description Photodynamic therapy (PDT) is used to treat malignancies and precancerous lesions. Near-infrared light delivered by lasers was thought for a while to be the most appropriate option to activate photosensitizers, mostly porphyrins, in the depth of the diseased tissues. More recently, however, several advantages including low cost and reduced adverse effects led to consider light emitting diodes (LED) and even daylight as an alternative to use PDT to treat accessible lesions. In this study we examined the capacity of OR141, a recently identified non-porphyrin photosensitizer (PS), to exert significant cytotoxic effects in various models of skin lesions and tumors upon white light activation. Using different cancer cell lines, we first identified LED lamp as a particularly suited source of light to maximize anti-proliferative effects of OR141. We then documented that OR141 diffusion and light penetration into tumor spheroids both reached thresholds compatible with the induction of cell death deep inside these 3D culture models. We further identified Arlasove as a clinically suitable solvent for OR141 that we documented by using Franz cells to support significant absorption of the PS through human skin. Finally, using topical but also systemic administration, we validated growth inhibitory effects of LED-activated OR141 in mouse skin tumor xenograft and precancerous lesions models. Altogether these results open clinical perspectives for the use of OR141 as an attractive PS to treat superficial skin malignant and non-malignant lesions using affordable LED lamp for photoactivation.
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spelling pubmed-61605392018-10-08 Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions Doix, Bastien Bastien, Estelle Rambaud, Alix Pinto, Adán Louis, Caroline Grégoire, Vincent Riant, Olivier Feron, Olivier Front Oncol Oncology Photodynamic therapy (PDT) is used to treat malignancies and precancerous lesions. Near-infrared light delivered by lasers was thought for a while to be the most appropriate option to activate photosensitizers, mostly porphyrins, in the depth of the diseased tissues. More recently, however, several advantages including low cost and reduced adverse effects led to consider light emitting diodes (LED) and even daylight as an alternative to use PDT to treat accessible lesions. In this study we examined the capacity of OR141, a recently identified non-porphyrin photosensitizer (PS), to exert significant cytotoxic effects in various models of skin lesions and tumors upon white light activation. Using different cancer cell lines, we first identified LED lamp as a particularly suited source of light to maximize anti-proliferative effects of OR141. We then documented that OR141 diffusion and light penetration into tumor spheroids both reached thresholds compatible with the induction of cell death deep inside these 3D culture models. We further identified Arlasove as a clinically suitable solvent for OR141 that we documented by using Franz cells to support significant absorption of the PS through human skin. Finally, using topical but also systemic administration, we validated growth inhibitory effects of LED-activated OR141 in mouse skin tumor xenograft and precancerous lesions models. Altogether these results open clinical perspectives for the use of OR141 as an attractive PS to treat superficial skin malignant and non-malignant lesions using affordable LED lamp for photoactivation. Frontiers Media S.A. 2018-09-21 /pmc/articles/PMC6160539/ /pubmed/30298119 http://dx.doi.org/10.3389/fonc.2018.00393 Text en Copyright © 2018 Doix, Bastien, Rambaud, Pinto, Louis, Grégoire, Riant and Feron. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Doix, Bastien
Bastien, Estelle
Rambaud, Alix
Pinto, Adán
Louis, Caroline
Grégoire, Vincent
Riant, Olivier
Feron, Olivier
Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions
title Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions
title_full Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions
title_fullStr Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions
title_full_unstemmed Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions
title_short Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions
title_sort preclinical evaluation of white led-activated non-porphyrinic photosensitizer or141 in 3d tumor spheroids and mouse skin lesions
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160539/
https://www.ncbi.nlm.nih.gov/pubmed/30298119
http://dx.doi.org/10.3389/fonc.2018.00393
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