Boosting the Radiosensitizing and Photothermal Performance of Cu2-xSe Nanocrystals for Synergetic Radiophotothermal Therapy of Orthotopic Breast Cancer

The small difference between tumor and normal tissues in their responses to ionizing radiation has been a significant issue for radiotherapy of tumors. Herein, we report that dumbbell-shaped heterogeneous copper selenide-gold nanocrystals can serve as an efficient radiosensitizer for enhanced radiotherapy. The mean lethal dose of X-rays to 4T1 tumor cells can be drastically decreased about 40%, that is, decreasing from 1.81 to 1.10 Gy after culture with heterostructures. Due to the synergetic effect of heterostructures, the dose of X-rays is also much lower than those obtained from mixture of Cu2-xSe + Au nanoparticles (1.78 Gy), Cu2-xSe nanoparticles (1.72 Gy) and Au nanoparticles (1.50 Gy), respectively. We demonstrate that the sensitivity enhancement ratio of Cu2-xSe nanoparticles was significantly improved 45% (i.e., from 1.1 to 1.6) after the formation of heterostructures with gold. We also show that the heteronanocrystals exhibit an enhanced photothermal conversion efficiency, due to the synergetic interactions of localized surface plasmon resonance. These properties highly feature them as a multimodal imaging contrast agent (particularly for photoacoustic imaging, computed tomography imaging, and single photon emission computed tomography after labeled with radioisotopes) and as a radiosensitizer for imaging guided synergetic radiophotothermal treatment of cancer. The research provides insights for engineering low-Z nanomaterials with high-Z elements to form heteronanostructures with enhanced synergetic performance for tumor theranostics.