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Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity

Photodynamic therapy (PDT) is a promising therapeutic modality which uses a photosensitizer to capture visible light resulting in phototoxicity in the irradiated region. PDT has been used in a number of pathological indications, including tumor. A key desirable feature of the photosensitizer is the...

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Autores principales: Xu, Peng, Chen, Jincan, Chen, Zhuo, Zhou, Shanyong, Hu, Ping, Chen, Xueyuan, Huang, Mingdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365043/
https://www.ncbi.nlm.nih.gov/pubmed/22693566
http://dx.doi.org/10.1371/journal.pone.0037051
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author Xu, Peng
Chen, Jincan
Chen, Zhuo
Zhou, Shanyong
Hu, Ping
Chen, Xueyuan
Huang, Mingdong
author_facet Xu, Peng
Chen, Jincan
Chen, Zhuo
Zhou, Shanyong
Hu, Ping
Chen, Xueyuan
Huang, Mingdong
author_sort Xu, Peng
collection PubMed
description Photodynamic therapy (PDT) is a promising therapeutic modality which uses a photosensitizer to capture visible light resulting in phototoxicity in the irradiated region. PDT has been used in a number of pathological indications, including tumor. A key desirable feature of the photosensitizer is the high phototoxicity on tumor cells but not on normal cells. In this study, we conjugate a gonadotropin-releasing hormone (GnRH) to a photosensitizer, Zinc phthalocyanine (ZnPc), in order to enhance its specificity to breast cancer, which over-expresses GnRH receptor. ZnPc has unique advantages over other photosensitizers, but is difficult to derivatize and purify as a single isomer. We previously developed a straight-forward way to synthesize mono-substituted β-carboxy-phthalocyanine zinc (ZnPc-COOH). Photophysical and photochemical parameters of this ZnPc-GnRH conjugate including fluorescence quantum yield (Ф(f)), fluorescence decay time (τ(s)) and singlet oxygen quantum yield (Ф(Δ)) were evaluated and found comparable with that of ZnPc, indicating that addition of a GnRH peptide does not significantly alter the generation of singlet oxygen from ZnPc. Cellular uptakes and phototoxicities of this conjugate were tested and found significantly enhanced on human breast cancer cell lines overexpressing GnRH receptors (MDA-MB-231 and MCF-7 cells) compared to cells with low levels of GnRH receptors, such as human embryonic lung fibroblast (HELF) and human liver carcinoma (HepG2) cells. In addition, the cellular uptake of this conjugate toward MCF-7 cells were found clearly alleviated by a GnRH receptor blocker Cetrorelix, suggesting that the cellular uptake of this conjugate was GnRH receptor-mediated. Put together, these findings revealed that coupling ZnPc with GnRH analogue was an effective way to improve the selectivity of ZnPc towards tumors with over-expressed GnRH receptors.
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spelling pubmed-33650432012-06-12 Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity Xu, Peng Chen, Jincan Chen, Zhuo Zhou, Shanyong Hu, Ping Chen, Xueyuan Huang, Mingdong PLoS One Research Article Photodynamic therapy (PDT) is a promising therapeutic modality which uses a photosensitizer to capture visible light resulting in phototoxicity in the irradiated region. PDT has been used in a number of pathological indications, including tumor. A key desirable feature of the photosensitizer is the high phototoxicity on tumor cells but not on normal cells. In this study, we conjugate a gonadotropin-releasing hormone (GnRH) to a photosensitizer, Zinc phthalocyanine (ZnPc), in order to enhance its specificity to breast cancer, which over-expresses GnRH receptor. ZnPc has unique advantages over other photosensitizers, but is difficult to derivatize and purify as a single isomer. We previously developed a straight-forward way to synthesize mono-substituted β-carboxy-phthalocyanine zinc (ZnPc-COOH). Photophysical and photochemical parameters of this ZnPc-GnRH conjugate including fluorescence quantum yield (Ф(f)), fluorescence decay time (τ(s)) and singlet oxygen quantum yield (Ф(Δ)) were evaluated and found comparable with that of ZnPc, indicating that addition of a GnRH peptide does not significantly alter the generation of singlet oxygen from ZnPc. Cellular uptakes and phototoxicities of this conjugate were tested and found significantly enhanced on human breast cancer cell lines overexpressing GnRH receptors (MDA-MB-231 and MCF-7 cells) compared to cells with low levels of GnRH receptors, such as human embryonic lung fibroblast (HELF) and human liver carcinoma (HepG2) cells. In addition, the cellular uptake of this conjugate toward MCF-7 cells were found clearly alleviated by a GnRH receptor blocker Cetrorelix, suggesting that the cellular uptake of this conjugate was GnRH receptor-mediated. Put together, these findings revealed that coupling ZnPc with GnRH analogue was an effective way to improve the selectivity of ZnPc towards tumors with over-expressed GnRH receptors. Public Library of Science 2012-05-31 /pmc/articles/PMC3365043/ /pubmed/22693566 http://dx.doi.org/10.1371/journal.pone.0037051 Text en Xu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xu, Peng
Chen, Jincan
Chen, Zhuo
Zhou, Shanyong
Hu, Ping
Chen, Xueyuan
Huang, Mingdong
Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity
title Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity
title_full Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity
title_fullStr Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity
title_full_unstemmed Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity
title_short Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity
title_sort receptor-targeting phthalocyanine photosensitizer for improving antitumor photocytotoxicity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365043/
https://www.ncbi.nlm.nih.gov/pubmed/22693566
http://dx.doi.org/10.1371/journal.pone.0037051
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