Porphyrin-coated gold nanoparticles associated with X-rays and proton therapy in the treatment of triple-negative breast cancer

). The combined treatment was evaluated for its effects on singlet oxygen generation, reactive oxygen species (ROS) production, mitochondrial membrane potential, and cell death pathways. Additionally, we assessed the survival fraction of both healthy and tumor breast cells. A 3D spheroid model was employed to further investigate the efficacy of the AuNPs@TMPyP-mediated PDT in combination with RT. Intracellular uptake of AuNPs@TMPyP significantly impaired antioxidant defenses, through reduction of thioredoxin reductase levels. Under combined treatment, we observed increased ROS production, reduced survival fraction, and loss of mitochondrial membrane potential, along with increased apoptosis. Our findings suggest that AuNPs@TMPyP-mediated PDT significantly enhances radiosensitization and amplifies the therapeutic response when combined with either X-rays or PT, while exhibiting selectivity toward tumor cells, positioning it as a promising strategy for treating TNBC.