Liposome-mediated delivery of a ruthenium-based metallodrug to overcome cisplatin resistance in osteosarcoma

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.