Laser-triggered aggregated cubic α-Fe₂O₃@Au nanocomposites for magnetic resonance imaging and photothermal/enhanced radiation synergistic therapy

Theranostic nanoparticles (NPs) have recently generated substantial interest in translational cancer research due to their capabilities for multimodal diagnostic imaging and anti-cancer therapy. We herein developed cubic alpha-iron(III) oxide (α-Fe₂O₃) nanoparticles coated with ultrasmall gold nanoseeds, abbreviated as α-Fe₂O₃@Au, for the synergistic treatment of radiotherapy and photothermal therapy in breast cancer. The resultant NPs, with an average diameter of 49 nm, exhibited satisfactory biosafety profiles and provided tumor contrast in T₂-weighted magnetic resonance (MR) imaging. The coating of ultrasmall Au nanoseeds exhibited strong absorption of near-infrared (NIR) laser that enabled to an efficacious photothermal therapy. It also sensitized radiotherapy, X-ray in this study, by generating large quantities of tumoricidal reactive oxygen species (ROS). Moreover, with the aid of NIR laser irradiation, the α-Fe₂O₃ substrate showed partial ablation and the Au NPs on its surface aggregated into a larger size (~13 nm), which has been proven to be the optimized size for radiotherapy. When tested in 4T1 murine breast cancer model, the α-Fe₂O₃@Au NPs significantly suppressed tumor growth (P < 0.01) when irradiated with a low-power laser (1.5 W/cm² for 3 min) and an intermediate X-ray dose (6 Gy). Our results demonstrate that α-Fe₂O₃@Au, integrated with MRI, photothermal therapy, and radiosensitization, is a promising multifunctional theranostic nanomedicine for clinical applications.