Functionalized Au@Cu-Sb-S Nanoparticles for Spectral CT/Photoacoustic Imaging-Guided Synergetic Photo-Radiotherapy in Breast Cancer.
Functionalized Au@Cu-Sb-S Nanoparticles for Spectral CT/Photoacoustic Imaging-Guided Synergetic Photo-Radiotherapy in Breast Cancer.
复制标题
功能化 Au@Cu-Sb-S 纳米粒子用于乳腺癌能谱 CT/光声成像引导协同光放射治疗
DOI：
10.2147/ijn.s338085
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发表时间：
2022
影响因子：
8
通讯作者：
Zhao B
中科院分区：
文献类型：
--
作者：
Hu H;Zheng S;Hou M;Zhu K;Chen C;Wu Z;Qi L;Ren Y;Wu B;Xu Y;Yan C;Zhao B
背景放射治疗(RT)是临床上公认的癌症治疗方法。然而，放射抵抗仍然是与RT失败相关的一个重要问题。最近，光疗诱导的放射增敏在转化性癌症研究中引起了人们的注意。方法制备包覆超细金纳米晶的铜-锑-S纳米粒子(Au@Cu-Sb-S)，并对其进行表征。评价了纳米粒子的生物安全性、近红外(NIR)激光吸收和辐射增强效应。对4T1乳腺癌荷瘤小鼠进行了体外和体内光谱计算机断层扫描(CT)和光声成像(PA)成像。通过体内肿瘤抑制实验对协同放光治疗进行评价。结果通过在铜-锑-S纳米颗粒表面原位生长Au纳米碳管，制备了Au@Cu-Sb-S纳米颗粒。细胞活力实验表明，当Sb浓度大于25ppm时，Au@Cu-Sb-S+近红外+RT组合对肿瘤细胞的杀伤作用明显强于其他处理。体内外光谱CT成像表明，Au@Cu-Sb-S纳米粒子的X射线衰减能力优于临床使用的碘，尤其是在较低的KeV水平下。Au@Cu-Sb-S纳米粒子表现出浓度依赖性和显著的PA信号增白效应。体内抑瘤研究表明，制备的Au@Cu-Sb-S纳米粒子对4T1乳腺癌小鼠经近红外激光照射和中等剂量(4GyX射线)照射后的肿瘤生长有显著抑制作用。结论Au@Cu-Sb-S与光谱CT、PA成像、光疗增强放射增敏相结合，是一种具有临床应用前景的多功能纳米治疗平台。
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.