State Key Laboratory for Modifcation of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai 201620, P. R. China.
Department of Interventional Radiology, Xinhua Hospital affiliated to Shanghai Jiaotong University , Shanghai 200080, P. R. China.
ACS Appl Mater Interfaces. 2018 Feb 21;10(7):6146-6154. doi: 10.1021/acsami.7b17107. Epub 2018 Feb 9.
We report the construction and characterization of Tc-labeled arginine-glycine-aspartic acid (RGD)-polyethylenimine (PEI) conjugates with entrapped gold nanoparticles in the cavities (RGD-Tc-Au PENPs) for dual-mode single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of an orthotopic hepatic carcinoma model. In this study, PEI was successively decorated with diethylenetriaminepentaacetic acid, poly(ethylene glycol) (PEG), and PEGylated RGD segments, and was utilized as an effective nanoplatform to entrap Au NPs and to be labeled with Tc. We showed that the designed RGD-Tc-Au PENPs displayed desirable colloidal stability and radiostability, and cytocompatibility in the investigated concentration range, and could be specifically uptaken by αβ integrin-overexpressing liver cancer cells in vitro. In vivo CT and SPECT imaging results indicated that the particles were able to be accumulated within an orthotopic hepatic carcinoma and displayed both CT and SPECT contrast enhancement in the tumor tissue. With the proven biocompatibility in vivo via histological examinations, the designed RGD-Tc-Au PENPs may be potentially employed as an effective nanoprobe for a highly efficient dual-mode SPECT/CT imaging of various αβ integrin-overexpressing tumors.
我们构建并表征了载钌放射性核素的精氨酸-甘氨酸-天冬氨酸（RGD）-聚亚乙基亚胺（PEI）缀合物，其中含有纳米金颗粒（RGD-Tc-Au PENPs），用于正位荷肝癌模型的单光子发射计算机断层扫描（SPECT）/计算机断层扫描（CT）双模式成像。在本研究中，PEI 被相继修饰上二乙三胺五乙酸、聚乙二醇（PEG）和聚乙二醇化 RGD 片段，被用作有效的纳米平台来包埋纳米金颗粒并被标记上钌。我们表明，设计的 RGD-Tc-Au PENPs 表现出良好的胶体稳定性、放射稳定性和在研究浓度范围内的细胞相容性，并且能够在体外被 αβ 整联蛋白过表达的肝癌细胞特异性摄取。体内 CT 和 SPECT 成像结果表明，这些颗粒能够在原位肝癌中积累，并在肿瘤组织中同时显示 CT 和 SPECT 对比增强。通过组织学检查证明了体内的生物相容性，设计的 RGD-Tc-Au PENPs 可能作为一种有效的纳米探针，用于各种 αβ 整联蛋白过表达肿瘤的高效 SPECT/CT 双模式成像。
