Bacteria-triggered liposomes for synergistic tumour therapy based on the hypoxic microenvironment

High-intensity focused ultrasound (HIFU) combined with chemotherapy has shown considerable promise in treating solid tumours. However, improving tumour ablation efficiency remains a major challenge due to multidrug resistance and lack of tumour selectivity. To solve this problem, we cleverly combine tumour-targeting anaerobic bacteria and hypoxia-activating prodrugs based on tumour hypoxia characteristics. Specifically, we first fabricated a novel platform utilizing cationic liposomes, functionalized with polyethylene glycol (PEG), that encapsulates hypoxia-activated prodrug tirapazamine (TPZ) and the HIFU synergist perfluorohexane (PFH), and these nanoparticles were combined with Bifidobacterium bifidum (B. bifidum) via electrostatic adsorption to fabricate a tumour-targeting system. We leveraged the advantages of B. bifidum that not only mediated nanoparticles effectively reach the tumour to realize better targeted synergistic therapy, but also induce hypoxia in tumorsby themselves in turn amplified the antitumour effect of TPZ. In vitro and in vivo experiments indicate that this strategy effectively promotes tumour cell apoptosis, inhibits tumour growth, and achieves ultrasound imaging. This therapy strategy holds great promise for cancer therapy and highlights the potential of using a combination of bacteria plus nanomedicine in future solid tumour therapy.