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功能化 Au@Cu-Sb-S 纳米粒子用于乳腺癌的光谱 CT/光声成像引导协同光热放疗。

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

机构信息

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.

出版信息

Int J Nanomedicine. 2022 Jan 25;17:395-407. doi: 10.2147/IJN.S338085. eCollection 2022.

DOI:10.2147/IJN.S338085
PMID:35115774
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8800589/
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.

摘要

背景

放射治疗(RT)是一种临床应用广泛的癌症治疗方法。然而,放射抵抗仍然是 RT 失败的一个重要问题。光疗诱导的放射增敏作用在转化癌症研究中最近引起了关注。

方法

合成并表征了包覆有超小金纳米晶(Au@Cu-Sb-S)的 Cu-Sb-S 纳米颗粒(NPs)。评估了 NPs 的生物安全性、近红外(NIR)激光的吸收和辐射增强效果。在 4T1 乳腺癌荷瘤小鼠中进行了体外和体内光谱计算机断层扫描(CT)成像和光声(PA)成像。通过体内肿瘤抑制研究评估了协同放化疗的效果。

结果

Au@Cu-Sb-S NPs 通过 Au NCs 在 Cu-Sb-S NPs 表面的原位生长制备而成。细胞活力实验表明,在浓度高于 25 ppm Sb 时,Au@Cu-Sb-S+NIR+RT 对肿瘤细胞的细胞毒性明显高于其他处理方式。体外和体内光谱 CT 成像表明,Au@Cu-Sb-S NPs 的 X 射线衰减能力优于临床使用的碘,特别是在较低的 keV 水平下。Au@Cu-Sb-S NPs 表现出浓度依赖性和显著的 PA 信号增强效应。体内肿瘤抑制研究表明,制备的 Au@Cu-Sb-S NPs 在接受 NIR 激光照射和中等 X 射线剂量(4 Gy)治疗的 4T1 乳腺癌荷瘤小鼠中显著抑制了肿瘤生长。

结论

这些结果表明,Au@Cu-Sb-S 与光谱 CT、PA 成像和光疗增强放射增敏相结合是一种有前途的多功能治疗纳米平台,可用于临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/81cbfc84541d/IJN-17-395-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/13dc8861321b/IJN-17-395-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/4076d457be4e/IJN-17-395-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/c47ccb89a59e/IJN-17-395-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/952e766d9b9c/IJN-17-395-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/81cbfc84541d/IJN-17-395-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/13dc8861321b/IJN-17-395-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/4076d457be4e/IJN-17-395-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/c47ccb89a59e/IJN-17-395-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/952e766d9b9c/IJN-17-395-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3492/8800589/81cbfc84541d/IJN-17-395-g0005.jpg

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