Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells

In cancer therapy, immunogenic cell death eliminates tumor cells more efficiently than conventional apoptosis. During photodynamic therapy (PDT), some photosensitizer (PS) targeting lysosomes divert apoptosis to the immunologically more relevant necrosis-like cell death. Acridine orange (AO) is a PS...

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Autores principales:	Csaba Bankó, Zsolt László Nagy, Miklós Nagy, Gábor György Szemán-Nagy, István Rebenku, László Imre, Attila Tiba, András Hajdu, János Szöllősi, Sándor Kéki, Zsolt Bacso
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	phototoxicity lysosome membrane permeability DNA damage QUINESIn method laser-scanning cytometry (LSC) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a74b4d986bc54330807323d3b2bc6a4a
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spelling	oai:doaj.org-article:a74b4d986bc54330807323d3b2bc6a4a2021-11-25T17:02:11ZIsocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells10.3390/cancers132256522072-6694https://doaj.org/article/a74b4d986bc54330807323d3b2bc6a4a2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5652https://doaj.org/toc/2072-6694In cancer therapy, immunogenic cell death eliminates tumor cells more efficiently than conventional apoptosis. During photodynamic therapy (PDT), some photosensitizer (PS) targeting lysosomes divert apoptosis to the immunologically more relevant necrosis-like cell death. Acridine orange (AO) is a PS targeting lysosome. We synthesized a new compound, 3-N,N-dimethylamino-6-isocyanoacridine (DM), a modified AO, aiming to target lysosomes better. To compare DM and AO, we studied optical properties, toxicity, cell internalization, and phototoxicity. In addition, light-mediated effects were monitored by the recently developed QUINESIn method on nuclei, and membrane stability, morphology, and function of lysosomes utilizing fluorescent probes by imaging cytometry in single cells. DM proved to be a better lysosomal marker at 405 nm excitation and lysed lysosomes more efficiently. AO injured DNA and histones more extensively than DM. Remarkably, DM’s optical properties helped visualize shockwaves of nuclear DNA released from cells during the PDT. The asymmetric polar modification of the AO leads to a new compound, DM, which has increased efficacy in targeting and disrupting lysosomes. Suitable AO modification may boost adaptive immune response making PDT more efficient.Csaba BankóZsolt László NagyMiklós NagyGábor György Szemán-NagyIstván RebenkuLászló ImreAttila TibaAndrás HajduJános SzöllősiSándor KékiZsolt BacsoMDPI AGarticlephototoxicitylysosome membrane permeabilityDNA damageQUINESIn methodlaser-scanning cytometry (LSC)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5652, p 5652 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	phototoxicity lysosome membrane permeability DNA damage QUINESIn method laser-scanning cytometry (LSC) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	phototoxicity lysosome membrane permeability DNA damage QUINESIn method laser-scanning cytometry (LSC) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Csaba Bankó Zsolt László Nagy Miklós Nagy Gábor György Szemán-Nagy István Rebenku László Imre Attila Tiba András Hajdu János Szöllősi Sándor Kéki Zsolt Bacso Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells
description	In cancer therapy, immunogenic cell death eliminates tumor cells more efficiently than conventional apoptosis. During photodynamic therapy (PDT), some photosensitizer (PS) targeting lysosomes divert apoptosis to the immunologically more relevant necrosis-like cell death. Acridine orange (AO) is a PS targeting lysosome. We synthesized a new compound, 3-N,N-dimethylamino-6-isocyanoacridine (DM), a modified AO, aiming to target lysosomes better. To compare DM and AO, we studied optical properties, toxicity, cell internalization, and phototoxicity. In addition, light-mediated effects were monitored by the recently developed QUINESIn method on nuclei, and membrane stability, morphology, and function of lysosomes utilizing fluorescent probes by imaging cytometry in single cells. DM proved to be a better lysosomal marker at 405 nm excitation and lysed lysosomes more efficiently. AO injured DNA and histones more extensively than DM. Remarkably, DM’s optical properties helped visualize shockwaves of nuclear DNA released from cells during the PDT. The asymmetric polar modification of the AO leads to a new compound, DM, which has increased efficacy in targeting and disrupting lysosomes. Suitable AO modification may boost adaptive immune response making PDT more efficient.
format	article
author	Csaba Bankó Zsolt László Nagy Miklós Nagy Gábor György Szemán-Nagy István Rebenku László Imre Attila Tiba András Hajdu János Szöllősi Sándor Kéki Zsolt Bacso
author_facet	Csaba Bankó Zsolt László Nagy Miklós Nagy Gábor György Szemán-Nagy István Rebenku László Imre Attila Tiba András Hajdu János Szöllősi Sándor Kéki Zsolt Bacso
author_sort	Csaba Bankó
title	Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells
title_short	Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells
title_full	Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells
title_fullStr	Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells
title_full_unstemmed	Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells
title_sort	isocyanide substitution in acridine orange shifts dna damage-mediated phototoxicity to permeabilization of the lysosomal membrane in cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a74b4d986bc54330807323d3b2bc6a4a
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Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells

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