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

Abstract

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 (Au@Cu-Sb-S) 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 Au@Cu-Sb-S 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 Au@Cu-Sb-S+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 Au@Cu-Sb-S NPs was superior to that of the clinically used Iodine, particularly at lower KeV levels. Au@Cu-Sb-S NPs showed a concentration-dependent and remarkable PA signal brightening effect. In vivo tumor inhibition studies showed that the prepared Au@Cu-Sb-S 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 Au@Cu-Sb-S integrated with spectral CT, PA imaging, and phototherapy-enhanced radiosensitization is a promising multifunctional theranostic nanoplatform for clinical applications.

Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway

“…There are many kinds of metal-based nanoparticles used for ionizing radiation sensitization, such as gold-based nanoparticles, 7 , 47 , 48 iron-based nanoparticles, 49 , 50 platinum-based nanoparticles 51 and gadolinium-based nanoparticles. 5 , 20 , 22 , 23 Recent studies have shown that gadolinium-based nanoparticles have significant potential for clinical application as they can be utilized as both MRI contrast agents and radiosensitizers to improve tumor killing.…”

High atomic number nanoparticles to enhance spectral CT imaging aspects

“…Furthermore, the Au@Cu–Sb–S NPs demonstrated superior X-ray attenuation and higher contrast than clinical iodine at 60, 100, and 140 keV at the tumor site at 24 h which was confirmed by photoacoustic imaging. 118…”

“…Furthermore, the Au@Cu-Sb-S NPs demonstrated superior X-ray attenuation and higher contrast than clinical iodine at 60, 100, and 140 keV at the tumor site at 24 h which was confirmed by photoacoustic imaging. 118 12. Challenges, future scope, and conclusion Spectral photon-counting CT imaging utilizing high-Z-elementbased nanostructures has shown promising outcomes in biomedical imaging.…”

The role of single‐walled carbon nanotubes functionalized with gold to increase radiosensitivity of cancer cells to X‐ray radiation

“…In another study, 4T1 cells were used to evaluate the cytotoxicity of Au@Cu‐Sb‐S nanoparticles + RT by the CCK‐8 method. Even at high concentrations (50 ppm Sb), cell viability remained above 75%, indicating negligible cytotoxicity of Au@Cu‐Sb‐S nanoparticles 22 . In the study by Hadi et al, Au@IONPs core‐shell nanoparticles were used as radiosensitizers to improve the effectiveness of radiation therapy in MCF‐7 cells.…”

“…Even at high concentrations (50 ppm Sb), cell viability remained above 75%, indicating negligible cytotoxicity of Au@Cu-Sb-S nanoparticles. 22 In the study by Hadi et al, Au@IONPs core-shell nanoparticles were used as radiosensitizers to improve the effectiveness of radiation therapy in MCF-7 cells. The results showed that cell survival decreased from 86.32% to 70.44% and from 77.50% to 57.28% for 2 and 4 Gy, respectively, which was significant.…”