Abstract

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-Fe 2 O 3 ) nanoparticles coated with ultrasmall gold nanoseeds, abbreviated as α-Fe 2 O 3 @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 T 2 -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-Fe 2 O 3 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-Fe 2 O 3 @Au NPs significantly suppressed tumor growth (P < 0.01) when irradiated with a low-power laser (1.5 W/cm 2 for 3 min) and an intermediate X-ray dose (6 Gy). Our results demonstrate that α-Fe 2 O 3 @Au, integrated with MRI, photothermal therapy, and radiosensitization , is a promising multifunctional theranostic nanomedicine for clinical applications.