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基于钆的亚 10nm 纳米粒子的绿色合成用于磁共振成像中的闪亮肾脏、肿瘤和荷瘤小鼠的血管生成。

Green Synthesis of Sub-10 nm Gadolinium-Based Nanoparticles for Sparkling Kidneys, Tumor, and Angiogenesis of Tumor-Bearing Mice in Magnetic Resonance Imaging.

机构信息

Institute of Photomedicine, Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai, 200443, China.

School of Materials Science and Engineering, School of Life Science, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin University, Tianjin, 300072, China.

出版信息

Adv Healthc Mater. 2017 Feb;6(4). doi: 10.1002/adhm.201600865. Epub 2016 Dec 22.

Abstract

Gadolinium (Gd)-based nanoparticles are known for their high potential in magnetic resonance imaging (MRI). However, further MRI applications of these nanoparticles are hampered by their relatively large sizes resulting in poor organ/tumor targeting. In this study, ultrafine sub-10 nm and biocompatible Gd-based nanoparticles are synthesized in a bioinspired, environmentally benign, and straightforward fashion. This novel green synthetic strategy is developed for growing dextran-coated Gd-based nanoparticles (GdNPs@Dex). The as-prepared GdNPs@Dex is not only biocompatible but also stable with a sub-10 nm size. It exhibits higher longitudinal and transverse relaxivities in water (r and r values of 5.43 and 7.502 s × 10 m of Gd , respectively) than those measured for Gd-DTPA solution (r and r values of 3.42 and 3.86 s × 10 m of Gd , respectively). In vivo dynamic T -weighted MRI in tumor-bearing mice shows GdNPs@Dex can selectively target kidneys and tumor, in addition to liver and spleen. GdNPs@Dex is found particularly capable for determining the tumor boundary with clearly enhanced tumor angiogenesis. GdNPs@Dex is also found cleared from body gradually mainly via hepatobiliary and renal processing with no obvious systemic toxicity. With this green synthesis strategy, the sub-10 nm GdNPs@Dex presents promising potentials for translational biomedical imaging applications.

摘要

基于钆的纳米颗粒因其在磁共振成像(MRI)中的高潜力而闻名。然而,由于这些纳米颗粒的相对较大尺寸,导致其在器官/肿瘤靶向方面的效果较差,因此进一步的 MRI 应用受到限制。在这项研究中,采用一种生物启发的、环境友好的、简单直接的方法合成了超细微的亚 10nm 和生物相容的基于钆的纳米颗粒。这种新颖的绿色合成策略是为生长葡聚糖包覆的基于钆的纳米颗粒(GdNPs@Dex)而开发的。所制备的 GdNPs@Dex 不仅具有生物相容性,而且还具有亚 10nm 的稳定性。它在水中表现出更高的纵向和横向弛豫率(r 和 r 值分别为 5.43 和 7.502 s × 10 m 的 Gd),高于 Gd-DTPA 溶液的测量值(r 和 r 值分别为 3.42 和 3.86 s × 10 m 的 Gd)。在荷瘤小鼠的体内动态 T1 加权 MRI 中,GdNPs@Dex 不仅可以选择性地靶向肾脏和肿瘤,还可以靶向肝脏和脾脏。研究发现,GdNPs@Dex 特别能够确定肿瘤边界,明显增强肿瘤血管生成。GdNPs@Dex 也被发现主要通过肝胆和肾脏处理逐渐从体内清除,没有明显的全身毒性。通过这种绿色合成策略,亚 10nm 的 GdNPs@Dex 为转化医学成像应用提供了有前途的潜力。

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