Functionalized Au@Cu-Sb-S Nanoparticles for Spectral CT/Photoacoustic Imaging-Guided Synergetic Photo-Radiotherapy in Breast Cancer

Background: Radiotherapy (RT) is clinically well-established cancer treatment. However, radioresistance remains a significant issue associated with failure of RT. Phototherapy-induced radiosensitization has recently attracted attention in translational cancer research. Methods: Cu-Sb-S nanoparticles (NPs) coated with ultra-small Au nanocrystals ( [email protected] ) were synthesized and characterized. The biosafety profiles, absorption of near-infrared (NIR) laser and radiation-enhancing effect of the NPs were evaluated. In vitro and in vivo spectral computed tomography (CT) imaging and photoacoustic (PA) imaging were performed in 4T1 breast cancer-bearing mice. The synergetic radio-phototherapy was assessed by in vivo tumor inhibition studies. Results: [email protected] NPs were prepared by in situ growth of Au NCs on the surface of Cu-Sb-S NPs. The cell viability experiments showed that the combination of [email protected] +NIR+RT was significantly more cytotoxic to tumor cells than the other treatments at concentrations above 25 ppm Sb. In vitro and in vivo spectral CT imaging demonstrated that the X-ray attenuation ability of [email protected] NPs was superior to that of the clinically used Iodine, particularly at lower KeV levels. [email protected] NPs showed a concentration-dependent and remarkable PA signal brightening effect. In vivo tumor inhibition studies showed that the prepared [email protected] NPs significantly suppressed tumor growth in 4T1 breast cancer-bearing mice treated with NIR laser irradiation and an intermediate X-ray dose (4 Gy). Conclusion: These results indicate that [email protected] integrated with spectral CT, PA imaging, and phototherapy-enhanced radiosensitization is a promising multifunctional theranostic nanoplatform for clinical applications. Keywords: [email protected] nanoparticle, phototherapy, radiotherapy, spectral CT, photoacoustic imaging