Magnetic nanoparticles with diblock glycopolymer shells give lectin concentration-dependent MRI signals and selective cell uptake
Magnetic nanoparticles with diblock glycopolymer shells give lectin concentration-dependent MRI signals and selective cell uptake
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DOI：
10.1039/c3sc52838c
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发表时间：
2014-01-01
期刊：
影响因子：
8.4
通讯作者：
Davis, Thomas P.
中科院分区：
文献类型：
--
作者：
Basuki, Johan S.;Esser, Lars;Davis, Thomas P.
多价糖聚合物对特定的凝集素蛋白表现出很强的亲和力，这取决于其特定的碳水化合物功能。在这项工作中，我们报告了一种简单的一锅法合成二嵌段PEG-糖共聚物，使用Cu（0）介导的活性自由基聚合和点击化学的组合将三种不同的碳水化合物，α-D-甘露糖，α-D-葡萄糖和β-D-葡萄糖连接到氧化铁纳米颗粒（IONP）表面。然后使用广泛的分析技术（包括ATR-FTIR、XPS和TEM）对所得IONP@P（OEGA）-b-P（糖）纳米颗粒进行广泛表征。有趣的是，当在9.4 T MRI中测量时，α-D-甘露糖官能化的IONP（IONP@P（OEGA）-b-P（N3 Man））表现出高的r（2）横向弛豫率。一个显着的变化T-2松弛后，观察到的凝集素伴刀豆球蛋白A（Con A）的结合，与凝集素浓度成正比的响应。本文报道的结果表明，凝集素与纳米颗粒表面的特异性结合可以使用MRI定量检测，显示出对未来诊断应用的重要前景。此外，我们发现在肺癌细胞系（A549）中，用α-D-甘露糖官能化的IONP的细胞摄取显著改善。
Multivalent glycopolymers exhibit a strong affinity for specific lectin proteins depending on their specific carbohydrate functionality. In this work, we report a facile one-pot synthesis of diblock PEG-glycopolymers using a combination of Cu(0) mediated living radical polymerization and click chemistry to attach three different carbohydrates, alpha-D-mannose, alpha-D-glucose and beta-D-glucose, to iron oxide nanoparticle (IONP) surfaces. The resultant IONP@P(OEGA)-b-P(sugar)nanoparticles were then extensively characterized using a wide range of analytical techniques, including ATR-FTIR, XPS and TEM. Interestingly, alpha-D-mannose functionalized IONPs, (IONP@P(OEGA)-b-P(N3Man)), exhibited high r(2) transverse relaxivity when measured in a 9.4 T MRI. A significant change in T-2 relaxation was observed following binding to the lectin concanavalin A (Con A), with a response proportional to the lectin concentration. The results reported herein indicate that the specific binding of lectin to nanoparticle surfaces can be quantitatively detected using MRI, showing significant promise for future diagnostic applications. Additionally we found a significant improvement in cell uptake for IONPs functionalized with alpha-D-mannose, in a lung cancer cell line (A549).