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载有疏水性钆螯合物的白蛋白纳米颗粒作为 T1-T2 双模态对比剂,用于准确的肝脏肿瘤成像。

Albumin-based nanoparticles loaded with hydrophobic gadolinium chelates as T-T dual-mode contrast agents for accurate liver tumor imaging.

机构信息

State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory for Chemical Biology of Fujian Province and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Department of Electronic Science and Fujian Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China.

出版信息

Nanoscale. 2017 Mar 30;9(13):4516-4523. doi: 10.1039/c7nr01134b.

Abstract

Magnetic resonance contrast agents with T-T dual mode contrast capability have attracted considerable interest because they offer complementary and synergistic diagnostic information, leading to high imaging sensitivity and accurate diagnosis. Here, we reported a facile strategy to construct albumin based nanoparticles loaded with hydrophobic gadolinium chelates by hydrophobic interaction for magnetic resonance imaging (MRI). We synthesized a glycyrrhetinic acid-containing Gd-DOTA derivative (GGD) and loaded GGD molecules into BSA nanoparticles to form GGD-BSA nanoparticles (GGD-BSA NPs). The large size and porous structure endow GGD-BSA NPs with geometrical confinement, which restricts the tumbling of GGD and the diffusion of surrounding water molecules. As a result, GGD-BSA NPs exhibit ultrahigh T and T relaxivities, which are approximately 8-fold higher than those of gadolinium-based clinical contrast agents at 0.5 T. Besides, due to the intrinsic properties of their components, GGD-BSA NPs show good biocompatibility in vitro and in vivo, which warrants their great potential in clinical translation. Furthermore, GGD-BSA NPs show remarkable sensitivity in noninvasive detection of liver tumors by self-confirmed T-T dual-mode contrast-enhanced MRI. All of these merits make GGD-BSA NPs a potential candidate for fruitful biomedical and preclinical applications.

摘要

具有 T-T 双重模式对比能力的磁共振对比剂引起了相当大的兴趣,因为它们提供了互补和协同的诊断信息,从而提高了成像灵敏度和准确诊断。在这里,我们报告了一种通过疏水性相互作用构建基于白蛋白的纳米粒子并将疏水性钆螯合物负载到纳米粒子中的简便策略,用于磁共振成像(MRI)。我们合成了一种含有甘草次酸的 Gd-DOTA 衍生物(GGD),并将 GGD 分子加载到 BSA 纳米粒子中形成 GGD-BSA 纳米粒子(GGD-BSA NPs)。大尺寸和多孔结构赋予 GGD-BSA NPs 几何约束,限制 GGD 的翻滚和周围水分子的扩散。结果,GGD-BSA NPs 表现出超高的 T1 和 T2 弛豫率,在 0.5 T 时,其弛豫率大约是基于钆的临床对比剂的 8 倍。此外,由于其成分的固有特性,GGD-BSA NPs 在体外和体内均表现出良好的生物相容性,这保证了它们在临床转化中的巨大潜力。此外,GGD-BSA NPs 通过自我证实的 T-T 双重模式对比增强 MRI 对肝肿瘤的非侵入性检测具有显著的敏感性。所有这些优点使 GGD-BSA NPs 成为有前途的生物医学和临床前应用的候选物。

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