PEGylated polyethylenimine as enhanced T₁ contrast agent for efficient magnetic resonance imaging.
PEGylated polyethylenimine as enhanced T₁ contrast agent for efficient magnetic resonance imaging.
复制标题
DOI：
10.1021/am5020875
复制
发表时间：
2014-07
影响因子：
9.5
通讯作者：
Sheng-yuan Zhou;Zhenkai Wu;Xiongsheng Chen;Lianshun Jia;Wei Zhu
中科院分区：
文献类型：
--
作者：
Sheng-yuan Zhou;Zhenkai Wu;Xiongsheng Chen;Lianshun Jia;Wei Zhu
目前临床上使用的小分子磁共振（MR）成像造影剂（CA）具有相对较短的半衰期，这限制了高分辨率器官和血管造影图像的采集。因此，开发一种简便的策略来合成具有转化潜力的长循环CA用于MR成像仍然是一个巨大的挑战。在这里，我们交流聚乙二醇化聚乙烯亚胺（PEI）的设计和合成及其作为增强T1 CA的应用，用于长循环血池以及有效的器官和肿瘤成像。在这项研究中，PEI与钆（Gd（III））螯合剂和mPEG-NHS共价接枝，然后对剩余的胺进行乙酰化，以改善生物相容性并延长循环时间。由于相对较长的循环时间（3.8 h），所形成的多功能PEI（PEI·NHAc-DTPA（Gd（III））-mPEG）可用作血池和主要器官成像的增强T1 CA，并且可在给药后96 h通过泌尿系统从体内清除。重要的是，PEI.NHAc-DTPA（Gd（III））-mPEG复合物通过增强的渗透和保留效应显示出用于肿瘤成像的强T1对比效应。这些结果表明，合成的PEI·NHAc-DTPA（Gd（III））-mPEG可用作各种生物系统的T1 MR成像的有希望的CA。
Currently used small molecular magnetic resonance (MR) imaging contrast agents (CAs) in clinics have relatively short half-lives, which has limited the acquisition of high-resolution organ and angiographic images. Therefore, development of a facile strategy for the synthesis of long-circulating CAs with the transforming potential for MR imaging still remains a great challenge. Here we communicate the design and synthesis of PEGylated polyethylenimine (PEI) and its application as enhanced T1 CA for the long-circulating blood pool as well as efficient organ and tumor imaging. In this study, PEI was covalently grafted with gadolinium (Gd(III)) chelator and mPEG-NHS, followed by acetylation of the remaining amines to improve biocompatibility and prolong circulation time. With the relatively long circulation time (3.8 h), the formed multifunctional PEI (PEI.NHAc-DTPA(Gd(III))-mPEG) can be used as an enhanced T1 CA for blood pool and major organ imaging, and could be cleared from the body 96 h post administration through the urinary system. Importantly, the PEI.NHAc-DTPA(Gd(III))-mPEG complexes displayed a strong T1 contrast effect for tumor imaging through the enhanced permeation and retention effect. These findings suggest that the synthesized PEI.NHAc-DTPA(Gd(III))-mPEG may be used as a promising CA for T1 MR imaging of various biological systems.