Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light

Photodynamic therapy delivers more targeted cell killing than classical chemotherapy. It uses light-absorbing compounds, photosensitizers (PSs), to generate lethal reactive oxygen species (ROS) at sites of localized irradiation. Transition metal complexes are attractive PSs due to their photostabili...

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Detalles Bibliográficos
Autores: Jones, Callum G., Martínez Alonso, Marta, Gagg, Hannah, Kirby, Liam, Weinstein, Julia A., Bryant, Helen E.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Burgos (UBU)
Repositorio:Repositorio Institucional de la Universidad de Burgos (RIUBU)
OAI Identifier:oai:riubu.ubu.es:10259/11324
Acceso en línea:https://hdl.handle.net/10259/11324
Access Level:acceso abierto
Palabra clave:Fotoquimioterapia
Cáncer-Quimioterapia
Photochemotherapy
Cancer-Chemotherapy
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spelling Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible LightJones, Callum G.Martínez Alonso, MartaGagg, HannahKirby, LiamWeinstein, Julia A.Bryant, Helen E.FotoquimioterapiaCáncer-QuimioterapiaPhotochemotherapyCancer-ChemotherapyPhotodynamic therapy delivers more targeted cell killing than classical chemotherapy. It uses light-absorbing compounds, photosensitizers (PSs), to generate lethal reactive oxygen species (ROS) at sites of localized irradiation. Transition metal complexes are attractive PSs due to their photostability, visible-light absorption, and high ROS yields. Here, we introduce a low-molecular weight, photostable iridium complex, [Ir(thpy)2(benz)]Cl, 1, that localizes to the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs visible light, phosphoresces strongly, generates 1O2 with 43% yield, and undergoes cellular elimination after 24 h. 1 shows low dark toxicity and under remarkably low doses (3 min, 20–30 mJ s–1 cm–2) of 405 or 455 nm light, it causes killing of bladder (EJ), malignant melanoma (A375), and oropharyngeal (OPSCC72) cancer cells, with high phototoxic indices > 100–378. 1 is also an efficient PS in 3D melanoma spheroids, with repeated short-time irradiation causing cumulative killing.Funded by The University of Sheffield, Rosetrees Trust M698, Wellcome Trust WT093134AIA, the EPSRC, and the Fundacioń Alfonso Martí n Escudero (Spain).American Chemical Society202620262024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/10259/11324reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU)instname:Universidad de Burgos (UBU)InglésJournal of Medicinal Chemistry. 2024, V. 67, n. 18, p. 16157–16164https://doi.org/10.1021/acs.jmedchem.4c00869Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riubu.ubu.es:10259/113242026-05-28T07:56:11Z
dc.title.none.fl_str_mv Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
title Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
spellingShingle Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
Jones, Callum G.
Fotoquimioterapia
Cáncer-Quimioterapia
Photochemotherapy
Cancer-Chemotherapy
title_short Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
title_full Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
title_fullStr Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
title_full_unstemmed Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
title_sort Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light
dc.creator.none.fl_str_mv Jones, Callum G.
Martínez Alonso, Marta
Gagg, Hannah
Kirby, Liam
Weinstein, Julia A.
Bryant, Helen E.
author Jones, Callum G.
author_facet Jones, Callum G.
Martínez Alonso, Marta
Gagg, Hannah
Kirby, Liam
Weinstein, Julia A.
Bryant, Helen E.
author_role author
author2 Martínez Alonso, Marta
Gagg, Hannah
Kirby, Liam
Weinstein, Julia A.
Bryant, Helen E.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Fotoquimioterapia
Cáncer-Quimioterapia
Photochemotherapy
Cancer-Chemotherapy
topic Fotoquimioterapia
Cáncer-Quimioterapia
Photochemotherapy
Cancer-Chemotherapy
description Photodynamic therapy delivers more targeted cell killing than classical chemotherapy. It uses light-absorbing compounds, photosensitizers (PSs), to generate lethal reactive oxygen species (ROS) at sites of localized irradiation. Transition metal complexes are attractive PSs due to their photostability, visible-light absorption, and high ROS yields. Here, we introduce a low-molecular weight, photostable iridium complex, [Ir(thpy)2(benz)]Cl, 1, that localizes to the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs visible light, phosphoresces strongly, generates 1O2 with 43% yield, and undergoes cellular elimination after 24 h. 1 shows low dark toxicity and under remarkably low doses (3 min, 20–30 mJ s–1 cm–2) of 405 or 455 nm light, it causes killing of bladder (EJ), malignant melanoma (A375), and oropharyngeal (OPSCC72) cancer cells, with high phototoxic indices > 100–378. 1 is also an efficient PS in 3D melanoma spheroids, with repeated short-time irradiation causing cumulative killing.
publishDate 2024
dc.date.none.fl_str_mv 2024
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10259/11324
url https://hdl.handle.net/10259/11324
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Medicinal Chemistry. 2024, V. 67, n. 18, p. 16157–16164
https://doi.org/10.1021/acs.jmedchem.4c00869
dc.rights.none.fl_str_mv Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU)
instname:Universidad de Burgos (UBU)
instname_str Universidad de Burgos (UBU)
reponame_str Repositorio Institucional de la Universidad de Burgos (RIUBU)
collection Repositorio Institucional de la Universidad de Burgos (RIUBU)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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