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超小 Gd2O3 纳米颗粒表面涂层的调控以改善 T1 加权磁共振成像。

Manipulating the surface coating of ultra-small Gd2O3 nanoparticles for improved T1-weighted MR imaging.

机构信息

Department of Materials Science & Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, 117574 Singapore.

Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, 11 Biopolis Way, #02-02, Helios 138667, Singapore.

出版信息

Biomaterials. 2014 Feb;35(5):1636-42. doi: 10.1016/j.biomaterials.2013.11.032. Epub 2013 Nov 26.

Abstract

In this report, monodispersed ultra-small Gd2O3 nanoparticles capped with hydrophobic oleic acid (OA) were synthesized with average particle size of 2.9 nm. Two methods were introduced to modify the surface coating to hydrophilic for bio-applications. With a hydrophilic coating, the polyvinyl pyrrolidone (PVP) coated Gd2O3 nanoparticles (Gd2O3-PVP) showed a reduced longitudinal T1 relaxation time compared with OA and cetyltrimethylammonium bromide (CTAB) co-coated Gd2O3 (Gd2O3-OA-CTAB) in the relaxation study. The Gd2O3-PVP was thus chosen for its further application study in MRI with an improved longitudinal relaxivity r1 of 12.1 mM(-1) s(-1) at 7 T, which is around 3 times as that of commercial contrast agent Magnevist(®). In vitro cell viability in HK-2 cell indicated negligible cytotoxicity of Gd2O3-PVP within preclinical dosage. In vivo MR imaging study of Gd2O3-PVP nanoparticles demonstrated considerable signal enhancement in the liver and kidney with a long blood circulation time. Notably, the OA capping agent was replaced by PVP through ligand exchange on the Gd2O3 nanoparticle surface. The hydrophilic PVP grants the Gd2O3 nanoparticles with a polar surface for bio-application, and the obtained Gd2O3-PVP could be used as an in vivo indicator of reticuloendothelial activity.

摘要

在本报告中,合成了平均粒径为 2.9nm 的单分散超小 Gd2O3 纳米粒子,并用疏水性油酸(OA)进行了包覆。介绍了两种方法将表面包覆物改性为亲水性,以用于生物应用。具有亲水性包覆层的聚乙烯吡咯烷酮(PVP)包覆的 Gd2O3 纳米粒子(Gd2O3-PVP)在弛豫研究中表现出比油酸和十六烷基三甲基溴化铵(CTAB)共包覆的 Gd2O3(Gd2O3-OA-CTAB)更低的纵向 T1 弛豫时间。因此,选择 Gd2O3-PVP 进行进一步的 MRI 应用研究,在 7T 下其纵向弛豫率 r1 为 12.1mM(-1)s(-1),约为商业对比剂 Magnevist(®)的 3 倍。HK-2 细胞的体外细胞活力研究表明,Gd2O3-PVP 的细胞毒性可忽略不计,其临床前剂量范围内。Gd2O3-PVP 纳米粒子的体内磁共振成像研究表明,在肝脏和肾脏中具有相当大的信号增强,并且具有较长的血液循环时间。值得注意的是,通过 Gd2O3 纳米粒子表面的配体交换,将亲脂性的 OA 封端剂替换为 PVP。亲水性 PVP 赋予 Gd2O3 纳米粒子具有亲生物应用的极性表面,并且所获得的 Gd2O3-PVP 可以用作网状内皮活性的体内指示剂。

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