Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands

Ir(III) and Ru(II) polypyridyl complexes are promising photosensitizers (PSs) for photodynamic therapy (PDT) due to their outstanding photophysical properties. Herein, one series of cyclometallated Ir(III) complexes and two series of Ru(II) polypyridyl derivatives bearing three different thiazolyl-β...

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Autores: Sanz-Villafruela, Juan, Bermejo-Casadesús, Cristina, Zafon, Elisenda, Martínez Alonso, Marta, Durá, Gema, Heras, Aranzazu, Soriano-Díaz, Iván, Giussani, Angelo, Ortí, Enrique, Tebar, Francesc, Espino, Gustavo, Massaguer i Vall-llovera, Anna
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/25118
Acesso em linha:http://hdl.handle.net/10256/25118
Access Level:Acceso aberto
Palavra-chave:Càncer -- Tractament
Cancer -- Treatment
Fotosensibilització (Biologia)
Photosensitization, Biological
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dc.title.none.fl_str_mv Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
title Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
spellingShingle Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
Sanz-Villafruela, Juan
Càncer -- Tractament
Cancer -- Treatment
Fotosensibilització (Biologia)
Photosensitization, Biological
title_short Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
title_full Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
title_fullStr Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
title_full_unstemmed Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
title_sort Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
dc.creator.none.fl_str_mv Sanz-Villafruela, Juan
Bermejo-Casadesús, Cristina
Zafon, Elisenda
Martínez Alonso, Marta
Durá, Gema
Heras, Aranzazu
Soriano-Díaz, Iván
Giussani, Angelo
Ortí, Enrique
Tebar, Francesc
Espino, Gustavo
Massaguer i Vall-llovera, Anna
author Sanz-Villafruela, Juan
author_facet Sanz-Villafruela, Juan
Bermejo-Casadesús, Cristina
Zafon, Elisenda
Martínez Alonso, Marta
Durá, Gema
Heras, Aranzazu
Soriano-Díaz, Iván
Giussani, Angelo
Ortí, Enrique
Tebar, Francesc
Espino, Gustavo
Massaguer i Vall-llovera, Anna
author_role author
author2 Bermejo-Casadesús, Cristina
Zafon, Elisenda
Martínez Alonso, Marta
Durá, Gema
Heras, Aranzazu
Soriano-Díaz, Iván
Giussani, Angelo
Ortí, Enrique
Tebar, Francesc
Espino, Gustavo
Massaguer i Vall-llovera, Anna
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Càncer -- Tractament
Cancer -- Treatment
Fotosensibilització (Biologia)
Photosensitization, Biological
topic Càncer -- Tractament
Cancer -- Treatment
Fotosensibilització (Biologia)
Photosensitization, Biological
description Ir(III) and Ru(II) polypyridyl complexes are promising photosensitizers (PSs) for photodynamic therapy (PDT) due to their outstanding photophysical properties. Herein, one series of cyclometallated Ir(III) complexes and two series of Ru(II) polypyridyl derivatives bearing three different thiazolyl-β-carboline N^N′ ligands have been synthesized, aiming to evaluate the impact of the different metal fragments ([Ir(C^N)2]+ or [Ru(N^N)2]2+) and N^N’ ligands on the photophysical and biological properties. All the compounds exhibit remarkable photostability under blue-light irradiation and are emissive (605 < λem < 720 nm), with the Ru(II) derivatives displaying higher photoluminescence quantum yields and longer excited state lifetimes. The Ir PSs display pKa values between 5.9 and 7.9, whereas their Ru counterparts are less acidic (pKa > 9.3). The presence of the deprotonated form in the Ir-PSs favours the generation of reactive oxygen species (ROS) since, according to theoretical calculations, it features a low-lying ligand-centered triplet excited state (T1 = 3LC) with a long lifetime. All compounds have demonstrated anticancer activity. Ir(III) complexes 1–3 exhibit the highest cytotoxicity in dark conditions, comparable to cisplatin. Their activity is notably enhanced by blue-light irradiation, resulting in nanomolar IC50 values and phototoxicity indexes (PIs) between 70 and 201 in different cancer cell lines. The Ir(III) PSs are also activated by green (with PI between 16 and 19.2) and red light in the case of complex 3 (PI = 8.5). Their antitumor efficacy is confirmed by clonogenic assays and using spheroid models. The Ir(III) complexes rapidly enter cells, accumulating in mitochondria and lysosomes. Upon photoactivation, they generate ROS, leading to mitochondrial dysfunction and lysosomal damage and ultimately cell apoptosis. Additionally, they inhibit cancer cell migration, a crucial step in metastasis. In contrast, Ru(II) complex 6 exhibits moderate mitochondrial activity. Overall, Ir(III) complexes 1–3 show potential for selective light-controlled cancer treatment, providing an alternative mechanism to chemotherapy and the ability to inhibit lethal cancer cell dissemination
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/25118
url http://hdl.handle.net/10256/25118
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2024.116618
info:eu-repo/semantics/altIdentifier/issn/0223-5234
info:eu-repo/semantics/altIdentifier/eissn/1768-3254
PID2021-127187OB-C22
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C22
dc.rights.none.fl_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv European Journal of Medicinal Chemistry, 2024, vol. 276, art. núm. 116618
Articles publicats (D-B)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligandsSanz-Villafruela, JuanBermejo-Casadesús, CristinaZafon, ElisendaMartínez Alonso, MartaDurá, GemaHeras, AranzazuSoriano-Díaz, IvánGiussani, AngeloOrtí, EnriqueTebar, FrancescEspino, GustavoMassaguer i Vall-llovera, AnnaCàncer -- TractamentCancer -- TreatmentFotosensibilització (Biologia)Photosensitization, BiologicalIr(III) and Ru(II) polypyridyl complexes are promising photosensitizers (PSs) for photodynamic therapy (PDT) due to their outstanding photophysical properties. Herein, one series of cyclometallated Ir(III) complexes and two series of Ru(II) polypyridyl derivatives bearing three different thiazolyl-β-carboline N^N′ ligands have been synthesized, aiming to evaluate the impact of the different metal fragments ([Ir(C^N)2]+ or [Ru(N^N)2]2+) and N^N’ ligands on the photophysical and biological properties. All the compounds exhibit remarkable photostability under blue-light irradiation and are emissive (605 < λem < 720 nm), with the Ru(II) derivatives displaying higher photoluminescence quantum yields and longer excited state lifetimes. The Ir PSs display pKa values between 5.9 and 7.9, whereas their Ru counterparts are less acidic (pKa > 9.3). The presence of the deprotonated form in the Ir-PSs favours the generation of reactive oxygen species (ROS) since, according to theoretical calculations, it features a low-lying ligand-centered triplet excited state (T1 = 3LC) with a long lifetime. All compounds have demonstrated anticancer activity. Ir(III) complexes 1–3 exhibit the highest cytotoxicity in dark conditions, comparable to cisplatin. Their activity is notably enhanced by blue-light irradiation, resulting in nanomolar IC50 values and phototoxicity indexes (PIs) between 70 and 201 in different cancer cell lines. The Ir(III) PSs are also activated by green (with PI between 16 and 19.2) and red light in the case of complex 3 (PI = 8.5). Their antitumor efficacy is confirmed by clonogenic assays and using spheroid models. The Ir(III) complexes rapidly enter cells, accumulating in mitochondria and lysosomes. Upon photoactivation, they generate ROS, leading to mitochondrial dysfunction and lysosomal damage and ultimately cell apoptosis. Additionally, they inhibit cancer cell migration, a crucial step in metastasis. In contrast, Ru(II) complex 6 exhibits moderate mitochondrial activity. Overall, Ir(III) complexes 1–3 show potential for selective light-controlled cancer treatment, providing an alternative mechanism to chemotherapy and the ability to inhibit lethal cancer cell disseminationThis work was supported by the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación of Spain (MCIN/AEI/10.13039/501100011033) (projects PID2021-127187OB-C21, PID2021-128569NB-I00, PID2020-115910RB-I00, PID2021-127187OB-C22, and CEX2019-000919-M). PhD students acknowledge their predoctoral grants to Universidad de Burgos (J.S.V., 2019/00002/008/001), University of Girona (C.B., IFUdG 2021), Generalitat de Catalunya (E.Z., AGAUR; 2021 FI_B 01036) and Generalitat Valenciana (I. S.D., CIACIF/2021/438), respectively. We thank M. Calvo, E. Coll and G. Martín and acknowledge the use of the Advanced Optical Microscopy Facility of the University of Barcelona (Spain)Open Access funding provided thanks to the CRUE-CSIC agreement with ElsevierElsevierAgencia Estatal de Investigación2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/25118European Journal of Medicinal Chemistry, 2024, vol. 276, art. núm. 116618Articles publicats (D-B)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2024.116618info:eu-repo/semantics/altIdentifier/issn/0223-5234info:eu-repo/semantics/altIdentifier/eissn/1768-3254PID2021-127187OB-C22info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C22Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/251182026-05-29T05:05:01Z
score 15,812429

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