School of Biological and Medical Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei, Anhui, 230009, PR China.
Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, CAS Centre for Excellence in Nanoscience, Hefei Science Centre of CAS, University of Science and Technology of China, Hefei, 230026, PR China.
Biomaterials. 2018 Mar;158:74-85. doi: 10.1016/j.biomaterials.2017.12.023. Epub 2017 Dec 28.
There is a great demand to develop high-relaxivity nanoscale contrast agents for magnetic resonance (MR) angiography with high resolution. However, there should be more focus on stability, ion leakage and excretion pathway of the intravenously injected nanoparticles, which are closely related to their clinic potentials. Herein, uniform ultrasmall-sized NaGdF nanocrystal (sub-10 nm) was synthesized using a facile high temperature organic solution method, and the nanocrystals were modified by a ligand-exchange approach using PEG-PAA di-block copolymer. The PEG-PAA modified NaGdF nanocrystal (denoted as ppNaGdF nanocrystal) exhibited a high r relaxivity which was twice of commercially used gadopentetate dimeglumine (Gd-DTPA) injection. MR angiography on rabbit using ppNaGdF nanocrystal at a low dose showed enhanced vascular details and long circulation time. Lyophilized powder of ppNaGdF nanocrystals have been successfully prepared without aggregation or reduction of MR performance, indicating the stability and an effective way to store this nanoscale contrast agent. No haemolysis was induced by ppNaGdF nanocrystal, and an extremely low leakage of gadolinium ions was confirmed. Furthermore, efficient renal excretion was one of the clearance pathways of ppNaGdF nanocrystal according to both the time dependent distribution data in blood and tissues and MR images. The in vivo toxicity evaluation further validated the great potential as a clinical agent for blood pool imaging.
开发用于磁共振（MR）血管造影的高分辨率高弛豫率纳米级对比剂的需求很大。然而，应该更加关注静脉注射纳米粒子的稳定性、离子泄漏和排泄途径，因为这些因素与它们的临床潜力密切相关。在此，我们使用简便的高温有机溶剂法合成了均匀的超小尺寸 NaGdF 纳米晶体（小于 10nm），并用 PEG-PAA 两亲嵌段共聚物通过配体交换法对纳米晶体进行了修饰。PEG-PAA 修饰的 NaGdF 纳米晶体（表示为 ppNaGdF 纳米晶体）表现出高 r 弛豫率，是市售的钆喷替酸葡甲胺（Gd-DTPA）注射液的两倍。使用 ppNaGdF 纳米晶体在低剂量下对兔子进行的 MR 血管造影显示出增强的血管细节和长循环时间。冻干的 ppNaGdF 纳米晶体粉末没有聚集或降低 MR 性能，表明其稳定性和储存这种纳米级对比剂的有效方法。ppNaGdF 纳米晶体不会引起溶血，并且证实了其镧系元素离子泄漏极低。此外，根据血液和组织中随时间变化的分布数据以及 MR 图像，高效的肾排泄是 ppNaGdF 纳米晶体的清除途径之一。体内毒性评估进一步验证了其作为血池成像的临床制剂的巨大潜力。
