CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging.

CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging.
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DOI:
10.1002/anie.201405442
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发表时间:
2014-09-01
影响因子:
16.6
通讯作者:
Long, Nicholas J.
Long, Nicholas J.
中科院分区:
化学1区
文献类型:
--
作者:
Gallo, Juan;Kamaly, Nazila;Lavdas, Ioannis;Stevens, Elizabeth;Quang-De Nguyen;Wylezinska-Arridge, Marzena;Aboagye, Eric O.;Long, Nicholas J.

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MRI具有很高的空间分辨率和良好的组织穿透性,但它的灵敏度有限,常用的对比剂缺乏特异性。在这项研究中,我们合成了两组氧化铁纳米颗粒(IONPs),它们被设计成在感应基质金属蛋白酶(MMP)酶时选择性地进行无铜的点击偶联,从而形成具有T2信号增强特性的自组装超顺磁性纳米团簇网络。为此,我们合成并表征了具有叠氮和炔表面的IONPs,其表面被连接到cxcr4靶向肽配体的聚乙二醇(PEG)层所掩盖。在体外测试了IONPs,当IONPs与表达MMP2/9和CXCR4的细胞孵育时,T2信号增强约160%。同时在荷瘤小鼠体内系统给予生物正交离子束,证明了这些“智能”自组装纳米材料的信号增强能力。
MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in vitro and T2 signal enhancements of around 160 % were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these ‘smart’ self-assembling nanomaterials.
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