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One-pot preparation of hydrophilic manganese oxide nanoparticles as T1 nano-contrast agent for molecular magnetic resonance imaging of renal carcinoma in vitro and in vivo
Biosensors and Bioelectronics ( IF 12.6 ) Pub Date : 2017-10-27 , DOI: 10.1016/j.bios.2017.10.047
Jingjing Li , Chen Wu , Pingfu Hou , Min Zhang , Kai Xu

Magnetic resonance imaging (MRI) contrast agents have become a necessary part for clinical practice to improve the sensitivity for the diagnosis of small lesions and injuries. Among them, manganese oxide nanoparticle (MnO NPs)-based MRI contrast agent attracts more and more attention because of their better performance in the detection of brain disease and positive enhancement in T1-weighted image. However, the relatively low r1 relaxivity and complex synthetic route hampered their wider applications. In this work, we proposed a one-pot approach to prepare hydrophilic MnO NPs via a polyol-like method with poly (ethylene glycol) (PEG) as both a solvent and surfactant. The obtained PEG-MnO NPs displayed a high T1 relaxivity and a low r2/r1 ratio (12.942 s−1 mM−1 and 4.66) at 3.0 T, which was three times that of the clinical used contrast agent, Magnevist (Gd-DTPA). Additionally, when exposed to the simulated body fluid (SBF), acidic environment or glutathione, PEG-MnO NPs kept stable, favoring their further biological applications. Then, to explore their use for the molecular magnetic resonance imaging of 786-0 renal carcinoma, amino group modified AS1411 aptamer as the targeting molecule was introduced to conjugate with PEG-MnO NPs via covalent coupling reaction. The fabricated nanoprobe, AS1411-PEG-MnO, could clearly visualize 786-0 renal carcinoma cells with MRI in vitro. Furthermore, compared with PEG-MnO NPs, AS1411-PEG-MnO nanoprobe presented a prolonged retention in 786-0 renal carcinoma tumor in vivo. The intravenously injected nanoprobes were eventually excreted from the body through the renal clearance route. These results indicated the potential promising of PEG-MnO NPs as an alternative contrast agent in MRI scanning.



中文翻译:

一锅制备亲水性氧化锰纳米颗粒作为T 1纳米造影剂,用于体外和体内肾癌分子磁共振成像

磁共振成像(MRI)造影剂已成为临床实践中提高对小病变和损伤的诊断灵敏度的必要部分。其中,基于锰氧化物纳米颗粒(MnO NPs)的MRI造影剂由于其在脑疾病检测中的更好性能和T 1加权图像的正增强而受到越来越多的关注。但是,相对较低的r 1弛豫度和复杂的合成路线阻碍了它们的广泛应用。在这项工作中,我们提出了一种一锅法,通过类似多元醇的方法,以聚乙二醇(PEG)作为溶剂和表面活性剂,来制备亲水性MnO NP。所得的PEG-MnO NPs表现出高的T 1弛豫性和低的r 2/ r 1比率(12.942 s -1 mM -1和4.66)在3.0 T时,这是临床使用的对比剂Magnevist(Gd-DTPA)的三倍。另外,当暴露于模拟体液(SBF),酸性环境或谷胱甘肽中时,PEG-MnO NP保持稳定,有利于其进一步的生物学应用。然后,为了探索其在786-0肾癌的分子磁共振成像中的用途,引入了氨基修饰的AS1411适体作为靶向分子,通过共价偶联反应与PEG-MnO NPs共轭。所制备的纳米探针AS1411-PEG-MnO可以通过MRI清晰地可视化786-0肾癌细胞。此外,与PEG-MnO NPs相比,AS1411-PEG-MnO纳米探针在体内在786-0肾癌肿瘤中的保留时间更长。静脉注射的纳米探针最终通过肾脏清除途径从体内排出。这些结果表明PEG-MnO NPs在MRI扫描中作为替代造影剂的潜在前景。

更新日期:2017-10-27
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