JUAN SANZ-VILLAFRUELA

@ubu.es

University of Burgos

JUAN SANZ-VILLAFRUELA


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https://researchid.co/juanuskui
7

Scopus Publications

80

Scholar Citations

5

Scholar h-index

4

Scholar i10-index

Scopus Publications

  • π-Extended Ru–COUBPY Photosensitizers for In Vivo Anticancer Phototherapy Using One-Photon 780 nm Near-Infrared Light
    Diego Abad-Montero, Eduardo Izquierdo-García, Pierre Mesdom, Albert Gandioso, Elena de la Torre-Rubio, Manel Bosch, Juan Sanz-Villafruela, Alba Deyà, Marta Redrado, Valentin V. Novikov, José Luis Hernández, Jorge Galino, Marta E. Alberto, Antonio Francés-Monerris, Gilles Gasser, Vicente Marchán
    Journal of the American Chemical Society, 2025
    High Resolution Image Download MS PowerPoint Slide Photodynamic therapy (PDT) is a promising cancer treatment modality, offering precise spatial and temporal control of drug activation using light. However, clinical translation of current photosensitizers (PSs) is limited by inefficient activation at wavelengths within the phototherapeutic window, especially in the deep-red and near-infrared (NIR) region. NIR light provides advantages such as reduced absorption by endogenous chromophores, minimized tissue photodamage, and improved tissue penetration, highlighting the need for PSs to be activatable in this range. Herein, we report a novel series of ruthenium(II) polypyridyl complexes ( Ru4–7 ) featuring π-extended COUBPY ligands, designed via a vinylogation strategy and synthesized through an innovative postcoordination ligand assembly approach. This structural modification enhances molar absorptivity and red-shifts the absorption bands well into the NIR region without substantially compromising photostability. Complexes Ru4–7 efficiently generate both Type I and Type II reactive oxygen species, and their photodynamic activity, combined with preferential mitochondrial accumulation, leads to potent nanomolar phototoxicity against CT-26 colorectal cancer cells under deep-red and NIR irradiation, even under hypoxia. Notably, the lead complex Ru6 demonstrated strong in vivo phototoxicity in mice bearing subcutaneous CT-26 tumors, achieving significant tumor growth inhibition upon irradiation with 660 and 780 nm light. Ru6 thus represents one of the first Ru(II) polypyridyl complexes to exhibit robust in vivo PDT antitumor activity under one-photon NIR activation. Its broad wavelength activation profile further underscores its potential versatility for treating tumors of varying size and anatomical location depending on specific light penetration requirements. These findings mark a promising step toward next-generation PSs for treating deep-seated and hypoxic tumors.
  • Profiting from light-induced metal-to-metal intramolecular electron transfer: towards highly efficient heterodinuclear photosensitizers for photodynamic therapy
    Juan Sanz-Villafruela, Lisa-Marie Servos, Nicolás Montesdeoca, José V. Cuevas-Vicario, Artur J. Moro, João C. Lima, Marta Martínez-Alonso, Gustavo Espino, Johannes Karges
    Inorganic Chemistry Frontiers, 2025
    This study introduces a novel Ruthenium(ii)–Platinum(ii) bimetallic conjugate that undergoes intramolecular electron transfer upon light exposure, producing singlet oxygen with higher efficiency than the separate metal complexes.
  • Advanced strategies in the design of Ir(III) biscyclometalated complexes for PDT
    Juan Sanz-Villafruela, Arancha Carbayo, Marta Martínez-Alonso, Gustavo Espino
    Coordination Chemistry Reviews, 2025
  • Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
    Juan Sanz-Villafruela, Cristina Bermejo-Casadesús, Gerard Riesco-Llach, Mònica Iglesias, Marta Martínez-Alonso, Marta Planas, Lidia Feliu, Gustavo Espino, Anna Massaguer
    Inorganic Chemistry, 2024
    High Resolution Image Download MS PowerPoint Slide 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.
  • Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands
    Juan Sanz-Villafruela, Cristina Bermejo-Casadesus, Elisenda Zafon, Marta Martínez-Alonso, Gema Durá, Aranzazu Heras, Iván Soriano-Díaz, Angelo Giussani, Enrique Ortí, Francesc Tebar, Gustavo Espino, Anna Massaguer
    European Journal of Medicinal Chemistry, 2024
    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.
  • Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands
    Juan Sanz-Villafruela, Cristina Bermejo-Casadesús, Marta Martínez-Alonso, Artur Moro, João C. Lima, Anna Massaguer, Gustavo Espino
    Dalton Transactions, 2024
    By extending π-conjugation on the N^N ligand, we have found an efficient Ir(iii) photosensitizer for anticancer PDT, which shows a long-lived excited state, excellent 1O2 production and mitochondrial membrane depolarization activity.
  • One-pot photocatalytic transformation of indolines into 3-thiocyanate indoles with new Ir(iii) photosensitizers bearing β-carbolines
    Juan Sanz-Villafruela, Carmen Martínez-Alonso, Igor Echevarría, Mónica Vaquero, Arancha Carbayo, Jairo Fidalgo, Ana M. Rodríguez, José Vicente Cuevas-Vicario, João C. Lima, Artur J. Moro, Blanca R. Manzano, Félix A. Jalón, Gustavo Espino
    Inorganic Chemistry Frontiers, 2021
    Herein, we harness the combination of two photocatalytic reactions, promoted by new Ir(iii) photosensitizers, for the direct access to 3-thiocyanato indoles from indolines in a one-pot process.

RECENT SCHOLAR PUBLICATIONS

  • π-Extended Ru–COUBPY Photosensitizers for In Vivo Anticancer Phototherapy Using One-Photon 780 nm Near-Infrared Light
    D Abad-Montero, E Izquierdo-García, P Mesdom, A Gandioso, ...
    Journal of the American Chemical Society 147 (50), 46291-46304 , 2025
    2025
    Citations: 3
  • π-Extended Ru-COUBPY photosensitizers for in vivo anticancer phototherapy using one-photon 780 nm near-infrared light.
    J Galino, ME Alberto, A Francés-Monerris, G Gasser, V Marchán Sancho, ...
    American Chemical Society , 2025
    2025
  • Advanced strategies in the design of Ir (III) biscyclometalated complexes for PDT
    J Sanz-Villafruela, A Carbayo, M Martinez-Alonso, G Espino
    Coordination Chemistry Reviews 534, 216572 , 2025
    2025
    Citations: 23
  • Profiting from light-induced metal-to-metal intramolecular electron transfer
    J Sanz-Villafruela, LM Servos, N Montesdeoca, JV Cuevas-Vicario, ...
    2025
  • Profiting from light-induced metal-to-metal intramolecular electron transfer: towards highly efficient heterodinuclear photosensitizers for photodynamic therapy
    J Sanz-Villafruela, LM Servos, N Montesdeoca, JV Cuevas-Vicario, ...
    Inorganic Chemistry Frontiers 12 (19), 5770-5782 , 2025
    2025
    Citations: 2
  • Synthesis, characterization and biological evaluation of New β-carboline-based Ir (III) and Ru (II) Photosensitizers for anticancer photodynamic therapy
    J Sanz Villafruela
    2025
  • Insights into the anticancer photodynamic activity of Ir (III) and Ru (II) polypyridyl complexes bearing β-carboline ligands
    J Sanz-Villafruela, C Bermejo-Casadesus, E Zafon, M Martínez-Alonso, ...
    European Journal of Medicinal Chemistry 276, 116618 , 2024
    2024
    Citations: 21
  • Bombesin-Targeted Delivery of β-Carboline-Based Ir (III) and Ru (II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
    J Sanz-Villafruela, C Bermejo-Casadesus, G Riesco-Llach, M Iglesias, ...
    Inorganic Chemistry 63 (41), 19140-19155 , 2024
    2024
    Citations: 12
  • Towards efficient Ir (III) anticancer photodynamic therapy agents by extending π-conjugation on N^ N ligands
    J Sanz-Villafruela, C Bermejo-Casadesús, M Martínez-Alonso, A Moro, ...
    Dalton Transactions 53 (27), 11393-11409 , 2024
    2024
    Citations: 8
  • Complejos de Iridio (III)
    G Espino Ordóñez, M Carbayo Martín, M Vaquero Gutiérrez, ...
    Oficina Española de Patentes y Marcas , 2022
    2022
  • One-pot photocatalytic transformation of indolines into 3-thiocyanate indoles with new Ir (III) photosensitizers bearing β-carbolines
    J Sanz-Villafruela, C Martínez-Alonso, I Echevarría, M Vaquero, ...
    Inorganic Chemistry Frontiers 8 (5), 1253-1270 , 2021
    2021
    Citations: 11

MOST CITED SCHOLAR PUBLICATIONS

  • Advanced strategies in the design of Ir (III) biscyclometalated complexes for PDT
    J Sanz-Villafruela, A Carbayo, M Martinez-Alonso, G Espino
    Coordination Chemistry Reviews 534, 216572 , 2025
    2025
    Citations: 23
  • Insights into the anticancer photodynamic activity of Ir (III) and Ru (II) polypyridyl complexes bearing β-carboline ligands
    J Sanz-Villafruela, C Bermejo-Casadesus, E Zafon, M Martínez-Alonso, ...
    European Journal of Medicinal Chemistry 276, 116618 , 2024
    2024
    Citations: 21
  • Bombesin-Targeted Delivery of β-Carboline-Based Ir (III) and Ru (II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer
    J Sanz-Villafruela, C Bermejo-Casadesus, G Riesco-Llach, M Iglesias, ...
    Inorganic Chemistry 63 (41), 19140-19155 , 2024
    2024
    Citations: 12
  • One-pot photocatalytic transformation of indolines into 3-thiocyanate indoles with new Ir (III) photosensitizers bearing β-carbolines
    J Sanz-Villafruela, C Martínez-Alonso, I Echevarría, M Vaquero, ...
    Inorganic Chemistry Frontiers 8 (5), 1253-1270 , 2021
    2021
    Citations: 11
  • Towards efficient Ir (III) anticancer photodynamic therapy agents by extending π-conjugation on N^ N ligands
    J Sanz-Villafruela, C Bermejo-Casadesús, M Martínez-Alonso, A Moro, ...
    Dalton Transactions 53 (27), 11393-11409 , 2024
    2024
    Citations: 8
  • π-Extended Ru–COUBPY Photosensitizers for In Vivo Anticancer Phototherapy Using One-Photon 780 nm Near-Infrared Light
    D Abad-Montero, E Izquierdo-García, P Mesdom, A Gandioso, ...
    Journal of the American Chemical Society 147 (50), 46291-46304 , 2025
    2025
    Citations: 3
  • Profiting from light-induced metal-to-metal intramolecular electron transfer: towards highly efficient heterodinuclear photosensitizers for photodynamic therapy
    J Sanz-Villafruela, LM Servos, N Montesdeoca, JV Cuevas-Vicario, ...
    Inorganic Chemistry Frontiers 12 (19), 5770-5782 , 2025
    2025
    Citations: 2
  • π-Extended Ru-COUBPY photosensitizers for in vivo anticancer phototherapy using one-photon 780 nm near-infrared light.
    J Galino, ME Alberto, A Francés-Monerris, G Gasser, V Marchán Sancho, ...
    American Chemical Society , 2025
    2025
  • Profiting from light-induced metal-to-metal intramolecular electron transfer
    J Sanz-Villafruela, LM Servos, N Montesdeoca, JV Cuevas-Vicario, ...
    2025
  • Synthesis, characterization and biological evaluation of New β-carboline-based Ir (III) and Ru (II) Photosensitizers for anticancer photodynamic therapy
    J Sanz Villafruela
    2025
  • Complejos de Iridio (III)
    G Espino Ordóñez, M Carbayo Martín, M Vaquero Gutiérrez, ...
    Oficina Española de Patentes y Marcas , 2022
    2022