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...
| Authors: | ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2024 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10256/26380 |
| Online Access: | http://hdl.handle.net/10256/26380 |
| Access Level: | Open access |
| Keyword: | Pròstata -- Càncer -- Tractament Prostate -- Cancer -- Treatment Fotoquimioteràpia Photochemotherapy |
| _version_ | 1878742667323506688 |
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| author | Sanz-Villafruela, Juan |
| 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 |
| author_browse | Bermejo-Casadesús, Cristina Espino, Gustavo Feliu Soley, Lidia Iglesias Juncà, Mònica Martínez Alonso, Marta Massaguer i Vall-llovera, Anna Planas i Grabuleda, Marta Riesco-Llach, Gerard 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 |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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 |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_fa0ea2ffa30d4fef7dc7383db5d4998d |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10256/26380 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | American Chemical Society (ACS) |
| publisherStr | American Chemical Society (ACS) |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer 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 Pròstata -- Càncer -- Tractament Prostate -- Cancer -- Treatment Fotoquimioteràpia Photochemotherapy 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 This 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) http://hdl.handle.net/10256/26380 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Pròstata -- Càncer -- Tractament Prostate -- Cancer -- Treatment Fotoquimioteràpia Photochemotherapy |
| topic_facet | Pròstata -- Càncer -- Tractament Prostate -- Cancer -- Treatment Fotoquimioteràpia Photochemotherapy |
| url | http://hdl.handle.net/10256/26380 |