Liposome-mediated delivery of a ruthenium-based metallodrug to overcome cisplatin resistance in osteosarcoma
Year: 2026
Type: article
Abstract: The treatment of osteosarcoma has remained largely unchanged over the past decades. Its low incidence, predominantly affecting children and young adults, combined with marked biological heterogeneity, poses major challenges to the development of effective therapies, and currently approved regimens often yield variable responses. Additionally, the frequent emergence of drug-resistant phenotypes in these mesenchymal tumors further compromises treatment success. As a result, despite substantial research efforts, patients with osteosarcoma still face a poor prognosis, underscoring the urgent need for improved therapeutic strategies. Alongside doxorubicin and methotrexate, cisplatin is one of the primary first-line chemotherapeutic agents used for osteosarcoma. However, like other cytotoxic drugs, cisplatin is limited by severe systemic toxicity and the development of resistance. In this study, we investigated the antitumor potential of a novel ruthenium organometallic compound, Ru3, and its liposomal encapsulation as a nanomedicine approach to provide a safer and more effective alternative to platinum-based therapy for both cisplatin-resistant and parental osteosarcoma models. In vitro, both free and liposomal Ru3 displayed stronger cytotoxicity than cisplatin in most models, effectively reversing drug resistance. Ru3 formulations also maintained potent activity in 3D osteosarcoma spheroids and selectively targeted cancer stem cell–enriched tumorspheres. In vivo, treatment with liposomal Ru3 in mice bearing cisplatin-resistant xenografts produced superior therapeutic outcomes and was better tolerated than cisplatin, alleviating its systemic toxicity. Overall, these findings support ruthenium-based metallodrugs delivered via liposomes as promising alternatives to platinum-based chemotherapy for osteosarcoma management.
Source: Drug Delivery
Authors: Dzohara Murillo, Elena Domínguez-Jurado, Carmen Huergo, Borja Gallego, Paula Díez, Andrea Ferreras, Enol Álvarez-González, Verónica Rey, Mar Rodríguez‑Santamaría, Ana S. Indurain, Fernando de Andrés Segura, Iván Bravo, Ángel Ríos, Adela A. Fernández-Velasco, Iván Fernández-Vega, Carlos Alonso-Moreno, René Rodríguez
Institutions: Instituto de Investigación Sanitaria del Principado de Asturias, ORFEO-CINQA Research Network, University of Castilla-La Mancha, Universidad de Oviedo, Gobierno del Principado de Asturias, Hospital Universitario Central de Asturias, Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina y Biotecnología de Cantabria, Centro de Investigación Biomédica en Red de Cáncer
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,864
Funders: Ministerio de Ciencia, Innovación y Universidades, European Commission, Fundación Científica Asociación Española Contra el Cáncer, Ministerio de Ciencia e Innovación, Universidad de Castilla-La Mancha, Junta de Comunidades de Castilla-La Mancha, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación
Awards: G1090419241, G1104056697, G1105844351, G1146347386, G1401168639, G1855990336, G2309174360, G2525280235, G252646220, G2542987457, G2660406951, G2706946973, G3399340363, G3518538256, G4093352487, G410571670, G4212894969, G4227155976, G4228226468, G430777504, G4338831617, G4343753977, G451917667, G4740006153, G491712853, G512887384, G5195188938, G523076202, G5421974903, G5539308778, G5577226636, G5635532810, G5725366334, G5770774958, G593054264, G5967599077, G6033112984, G6603613172, G7361556201, G736899713, G7395345766, G7401793180, G7539518723, G7547645751, G7560615177, G7768106676, G7805626310, G7863371703, G7951387284, G800104512, G8386327637, G8434830731, G8497050386, G8575141037, G8667377315, G8871382881, G8920660035, G89668360, G99296377
OpenAlex ID: W7160952162