Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer

Despite advances in Ir(III) and Ru(II) photosensitizers (PSs), their lack of selectivity for cancer cells has hindered their use in photodynamic therapy (PDT). We disclose the synthesis and characterization of two pairs of Ir(III) and Ru(II) polypyridyl complexes bearing two β-carboline ligands (N^N...

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Autores: Sanz-Villafruela, Juan, Bermejo-Casadesús, Cristina, Riesco-Llach, Gerard, Massaguer i Vall-llovera, Anna, Iglesias Juncà, Mònica, Martínez Alonso, Marta, Planas i Grabuleda, Marta, Feliu Soley, Lidia, Espino, Gustavo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/26380
Acceso en línea:http://hdl.handle.net/10256/26380
Access Level:acceso abierto
Palabra clave:Pròstata -- Càncer -- Tractament
Prostate -- Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
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spelling Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate CancerSanz-Villafruela, JuanBermejo-Casadesús, CristinaRiesco-Llach, GerardMassaguer i Vall-llovera, AnnaIglesias Juncà, MònicaMartínez Alonso, MartaPlanas i Grabuleda, MartaFeliu Soley, LidiaEspino, GustavoMassaguer i Vall-llovera, AnnaPròstata -- Càncer -- TractamentProstate -- Cancer -- TreatmentFotoquimioteràpiaPhotochemotherapyDespite advances in Ir(III) and Ru(II) photosensitizers (PSs), their lack of selectivity for cancer cells has hindered their use in photodynamic therapy (PDT). We disclose the synthesis and characterization of two pairs of Ir(III) and Ru(II) polypyridyl complexes bearing two β-carboline ligands (N^N’) functionalized with −COOMe (L1) or −COOH (L2), resulting in PSs of formulas [Ir(C^N)2(N^N’)]Cl (Ir-Me: C^N = ppy, N^N’ = L1; Ir-H: C^N = ppy, N^N’ = L2) and [Ru(N^N)2(N^N’)](Cl)2 (Ru-Me: N^N = bpy, N^N’ = L1; Ru-H: N^N = bpy, N^N’ = L2). To enhance their selectivity toward cancer cells, Ir-H and Ru-H were coupled to a bombesin derivative (BN3), resulting in the metallopeptides Ir-BN and Ru-BN. Ir(III) complexes showed higher anticancer activity than their Ru(II) counterparts, particularly upon blue light irradiation, but lacked cancer cell selectivity. In contrast, Ir-BN and Ru-BN exhibited selective photocytoxicity against prostate cancer cells, with a lower effect against nonmalignant fibroblasts. All compounds generated ROS and induced severe mitochondrial toxicity upon photoactivation, leading to apoptosis. Additionally, the ability of Ir-Me to oxidize NADH was demonstrated, suggesting a mechanism for mitochondrial damage. Our findings indicated that the conjugation of metal PSs with BN3 creates efficient PDT agents, achieving selectivity through targeting bombesin receptors and local photoactivationThis work was supported by the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (MCIN/AEI) of Spain (projects PID2021-127187OB-C21 and PID2021-127187OB-C22/MCIN/AEI/10.13039/501100011033/FEDER, UE). PhD students acknowledge their predoctoral grants to Universidad de Burgos (J.S.V., 2019/00002/008/001) and University of Girona (C.B., IFUdG2021; G.R., IFUdG2020). Open Access funding provided thanks to the CRUE-CSIC agreement with American Chemical Society (ACS)American Chemical Society (ACS)Agencia Estatal de Investigación2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/26380Inorganic Chemistry, 2024, vol. 63, núm. 41, p. 19140-19155Articles 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/10.1021/acs.inorgchem.4c02583info:eu-repo/semantics/altIdentifier/issn/0020-1669info:eu-repo/semantics/altIdentifier/eissn/1520-510XPID2021-127187OB-C22info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C22Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/263802026-05-29T05:05:01Z
dc.title.none.fl_str_mv Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
title Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
spellingShingle Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
Sanz-Villafruela, Juan
Pròstata -- Càncer -- Tractament
Prostate -- Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
title_short Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
title_full Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
title_fullStr Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
title_full_unstemmed Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
title_sort Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
dc.creator.none.fl_str_mv Sanz-Villafruela, Juan
Bermejo-Casadesús, Cristina
Riesco-Llach, Gerard
Massaguer i Vall-llovera, Anna
Iglesias Juncà, Mònica
Martínez Alonso, Marta
Planas i Grabuleda, Marta
Feliu Soley, Lidia
Espino, Gustavo
Massaguer i Vall-llovera, Anna
author Sanz-Villafruela, Juan
author_facet Sanz-Villafruela, Juan
Bermejo-Casadesús, Cristina
Riesco-Llach, Gerard
Massaguer i Vall-llovera, Anna
Iglesias Juncà, Mònica
Martínez Alonso, Marta
Planas i Grabuleda, Marta
Feliu Soley, Lidia
Espino, Gustavo
author_role author
author2 Bermejo-Casadesús, Cristina
Riesco-Llach, Gerard
Massaguer i Vall-llovera, Anna
Iglesias Juncà, Mònica
Martínez Alonso, Marta
Planas i Grabuleda, Marta
Feliu Soley, Lidia
Espino, Gustavo
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Pròstata -- Càncer -- Tractament
Prostate -- Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
topic Pròstata -- Càncer -- Tractament
Prostate -- Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
description Despite advances in Ir(III) and Ru(II) photosensitizers (PSs), their lack of selectivity for cancer cells has hindered their use in photodynamic therapy (PDT). We disclose the synthesis and characterization of two pairs of Ir(III) and Ru(II) polypyridyl complexes bearing two β-carboline ligands (N^N’) functionalized with −COOMe (L1) or −COOH (L2), resulting in PSs of formulas [Ir(C^N)2(N^N’)]Cl (Ir-Me: C^N = ppy, N^N’ = L1; Ir-H: C^N = ppy, N^N’ = L2) and [Ru(N^N)2(N^N’)](Cl)2 (Ru-Me: N^N = bpy, N^N’ = L1; Ru-H: N^N = bpy, N^N’ = L2). To enhance their selectivity toward cancer cells, Ir-H and Ru-H were coupled to a bombesin derivative (BN3), resulting in the metallopeptides Ir-BN and Ru-BN. Ir(III) complexes showed higher anticancer activity than their Ru(II) counterparts, particularly upon blue light irradiation, but lacked cancer cell selectivity. In contrast, Ir-BN and Ru-BN exhibited selective photocytoxicity against prostate cancer cells, with a lower effect against nonmalignant fibroblasts. All compounds generated ROS and induced severe mitochondrial toxicity upon photoactivation, leading to apoptosis. Additionally, the ability of Ir-Me to oxidize NADH was demonstrated, suggesting a mechanism for mitochondrial damage. Our findings indicated that the conjugation of metal PSs with BN3 creates efficient PDT agents, achieving selectivity through targeting bombesin receptors and local photoactivation
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/10256/26380
url http://hdl.handle.net/10256/26380
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.inorgchem.4c02583
info:eu-repo/semantics/altIdentifier/issn/0020-1669
info:eu-repo/semantics/altIdentifier/eissn/1520-510X
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 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
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 (ACS)
publisher.none.fl_str_mv American Chemical Society (ACS)
dc.source.none.fl_str_mv Inorganic Chemistry, 2024, vol. 63, núm. 41, p. 19140-19155
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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score 15,81155

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