Multi-modal therapeutic action of gallium-containing bioactive glass against osteosarcoma and bacterial pathogens

Abstract

Despite multimodal therapy, bone tumours can lead to high morbidity and poor survival, with recurrent limited success from trials investigating targeted or immunotherapies. Surgery remains essential and is often the only option available for refractory disease, skeletal metastases, and some benign bone lesions. However, primary bone tumours, such as osteosarcoma, often recur locally when complete resection is hindered by limited safety margins or proximity to vital structures. A multifunctional biomaterial capable of eradicating residual tumour cells while promoting bone regeneration could significantly improve outcomes of surgical procedures in these clinical settings. Here, we report the anticancer and antibacterial properties of gallium-containing bioactive glasses (Ga-BGs). We show that osteosarcoma cell lines are especially sensitive to gallium and that Ga-BGs can release therapeutic levels of gallium ions that selectively kill osteosarcoma cells. Our mechanistic investigation reveals that gallium promotes a multi-pronged molecular attack on key hallmarks of cancer cells, primarily through disrupting iron metabolism leading to increased oxidative stress, induction of cell death pathways, and suppression of oncogenic and metastatic signalling. Moreover, gallium nitrate and Ga-BGs are shown to present inhibitory effects upon gram-negative bacteria P. aeruginosa. Taken together, our results indicate that Ga-BGs constitute a model biomaterial for the development of multi-functional scaffolds for the treatment of osteosarcoma.