Bacteria-based drug-loaded mesoporous silica nanoparticles for synergistic FUAS of breast cancer

Focused ultrasound ablation surgery (FUAS), a minimally invasive therapeutic strategy, has demonstrated potential in breast cancer treatment but is limited by incomplete tumor irradiation and the damage to normal tissues. Here, we present a novel platform utilizing mesoporous silica nanoparticles (MSNs), functionalized with polyethylene glycol (PEG) and polyethyleneimine (PEI), encapsulating astragaloside IV (AS) and gated with 1-tetradecanol (TD). These NPs (PP@M-TD/AS) attach to Bifidobacterium bifidum (BF) via electrostatic adsorption. Leveraging BF's tumor-targeting ability in hypoxic microenvironments, the NPs enable specific accumulation in tumor site, facilitating targeted and efficient drug delivery. FUAS-induced thermal effects trigger the phase transition of TD, facilitating on-demand AS release at the tumor site. This approach enhances FUAS-mediated tumor ablation by improving acoustic impedance and ensuring precise drug delivery, leading to significant tumor suppression. Moreover, the system exhibited extended retention at the tumor site and excellent biocompatibility with minimal systemic toxicity. This platform effectively addresses the limitations of FUAS, offering a highly efficient and targeted approach for advancing breast cancer therapy.