Department of Radiology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing 400042, People's Republic of China.
Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing 400042, People's Republic of China.
Int J Nanomedicine. 2019 Sep 26;14:7879-7889. doi: 10.2147/IJN.S211974. eCollection 2019.
Precisely and sensitively diagnosing diseases especially early and accurate tumor diagnosis in clinical magnetic resonance (MR) scanner is a highly demanding but challenging task. Gadolinium (Gd) chelate is the most common magnetic resonance imaging (MRI) contrast agent at present. However, traditional Gd-chelates are suffering from low relaxivity, which hampers its application in clinical diagnosis. Currently, the development of nano-sized Gd based contrast agent, such as incorporating gadolinium chelate into nanocarriers, is an attractive and feasible strategy to enhance the contrast capacity of Gd chelate. The objective of this study is to improve the contrast ability of Gd-chelate by synthesizing nanoparticles (NPs) for accurate and early diagnosis in clinical diseases.
Reverse microemulsion method was used to coat iron oxide (IO) with tunable silica shell and form cores of NPs IO@SiO at step one, then Gd-chelate was loaded on the surface of silica-coated iron oxide NPs. Finally, Gd-based silica coating magnetite NPs IO@SiO-DTPA-Gd was developed and tested the ability to detect tumor cells on the cellular and in vivo level.
The value of IO@SiO-DTPA-Gd NPs with the silica shell thickness of 12 nm was about 33.6 mMs, which was approximately 6 times higher than Gd-DTPA, and based on its high contrast ability, IO@SiO-DTPA-Gd NPs could effectively detect tumor cells on the cellular and in vivo level.
Our findings revealed the improvement of relaxation was not only because of the increase of molecular tumbling time caused by the IO@SiO nanocarrier but also the generated magnetic field caused by the IO core. This nanostructure with high contrast ability may open a new approach to construct high-performance contrast agent.
在临床磁共振（MR）扫描仪中精确而灵敏地诊断疾病，特别是早期准确地诊断肿瘤，是一项要求极高但极具挑战性的任务。镧系元素（Gd）螯合物是目前最常用的磁共振成像（MRI）对比剂。然而，传统的 Gd-螯合物的弛豫率较低，这限制了其在临床诊断中的应用。目前，开发纳米级 Gd 基对比剂，如将 Gd 螯合物掺入纳米载体中，是提高 Gd 螯合物对比能力的一种有吸引力和可行的策略。本研究的目的是通过合成纳米颗粒（NPs）来提高 Gd-螯合物的对比能力，以实现临床疾病的准确和早期诊断。
采用反相微乳液法在氧化铁（IO）表面包覆可调厚度的二氧化硅壳，形成 NPs IO@SiO 的核，然后将 Gd-螯合物负载在二氧化硅包覆的氧化铁 NPs 表面。最后，开发了基于 Gd 的二氧化硅包覆磁铁矿 NPs IO@SiO-DTPA-Gd，并在细胞和体内水平上测试了其检测肿瘤细胞的能力。
具有 12nm 厚二氧化硅壳的 IO@SiO-DTPA-Gd NPs 的 r1 值约为 33.6 mMs，约为 Gd-DTPA 的 6 倍，基于其高对比能力，IO@SiO-DTPA-Gd NPs 可有效检测细胞和体内水平的肿瘤细胞。
我们的研究结果表明，弛豫率的提高不仅是由于 IO@SiO 纳米载体增加了分子旋转时间，而且还由于 IO 核产生了磁场。这种具有高对比能力的纳米结构可能为构建高性能对比剂开辟新途径。
