Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging
Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging
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DOI：
10.1016/j.colsurfb.2021.111732
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发表时间：
2021-04-08
影响因子：
5.8
通讯作者：
Gonda, Kohsuke
中科院分区：
文献类型：
--
作者：
Inose, Tomoya;Kitamura, Narufumi;Gonda, Kohsuke
利用X线造影剂对肿瘤血管形态进行准确成像的技术对于阐明肿瘤进展的机制和评价化疗的疗效具有重要意义。然而，在临床实践中，与其它高原子序数元素相比，碘基造影剂存在诸如由于高清除能力和不足的X射线吸收能力而导致的短血液滞留的问题。为了解决这些问题，具有高原子序数的金纳米颗粒（AuNPs）作为用于血管造影的造影剂已经引起了极大的关注，并且已经在小动物模型中使用。在这里，我们开发了新的造影剂，使用金纳米粒子和捕获的肿瘤血管形态随时间的变化，使用X射线计算机断层扫描（CT）。首先，谷胱甘肽支持的单一纳米尺寸的金纳米粒子（sAu/GSH）（直径，2.2 nm），使用四（羟甲基）氯化鳞作为还原剂。将sAu/GSH颗粒静脉注射到小鼠体内，在血管中保留几分钟，然后在24小时后由肾脏排出，类似于商业造影剂碘帕醇。接着，通过在缩合剂的影响下向sAu/ GSH溶液中添加乳铁蛋白，制备Au/GSH和乳铁蛋白（sAu/GSH-LF）（长轴尺寸，17.3 nm）复合物。静脉注射sAu/GSH-LF后，血液滞留时间为1-3 h，明显长于碘帕醇和sAu/ GSH。此外，我们成功地成像形态学变化，在相同的肿瘤血管数天，使用X射线CT与sAu/GSH-LF。
The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/ GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1-3 h, which was considerably longer than that observed with iopamidol and sAu/ GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.