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Dual-targeting superparamagnetic iron oxide nanoprobes with high and low target density for brain glioma imaging

机译:具有高和低靶密度的双靶超顺磁性氧化铁纳米探针用于脑胶质瘤成像

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摘要

A major limit of superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic resonance (MR) imaging nanoprobe in clinical applications is that the SPIONs are unable to reach sufficient concentrations at the tumor site by passive targeting to produce an obvious contrast effect for tumor imaging. Single-targeting SPIONs systems have been applied to improve the contrast effect. However, they still suffer from a lack of efficiency and specificity of the SPIONs to tumors. Herein, we developed folic acid (FA) and cyclic Arg-Gly-Asp-D-Tyr-Lys (c(RGDyK)) dual-targeting nanoprobes based on Cy5.5 labeled Fe3O4 nanoparticles (NPs). The synergistic targeting ability of the dual-targeting Fe3O4 NPs and the effect of the dual-target density on targeting specificity were investigated in brain glioma-bearing mice. In vivo T-2-weighted MR imaging of brain glioma-bearing mice and ex vivo near-infrared imaging of brains harboring gliomas suggested that the combination of dual-target increased the uptake of NPs by glioma, consequently, enhanced the contrast effect. Moreover, it was revealed that the density of dual-target plays an important role in targeting specificity. (C) 2016 Elsevier Inc. All rights reserved.
机译:在临床应用中,超顺磁性氧化铁纳米粒子(SPIONs)作为磁共振(MR)成像纳米探针的主要局限在于,SPIONs无法通过被动靶向在肿瘤部位达到足够的浓度,从而无法为肿瘤成像产生明显的对比效果。单目标SPIONs系统已用于改善对比度效果。然而,它们仍然遭受SPIONs对肿瘤缺乏效率和特异性的困扰。在本文中,我们开发了基于Cy5.5标记的Fe3O4纳米颗粒(NPs)的叶酸(FA)和环状Arg-Gly-Asp-D-Tyr-Lys(c(RGDyK))双靶纳米探针。研究了双靶向Fe3O4 NPs的协同靶向能力以及双靶向密度对靶向脑胶质瘤小鼠靶向特异性的影响。携带脑神经胶质瘤的小鼠的体内T-2加权MR成像和包含神经胶质瘤的脑的离体近红外成像表明,双靶点的组合可增加神经胶质瘤对NP的吸收,从而增强对比效果。此外,揭示了双重靶标的密度在靶向特异性中起重要作用。 (C)2016 Elsevier Inc.保留所有权利。

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