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MRI contrast agent for molecular imaging of the HER2eu receptor using targeted magnetic nanoparticles

机译:MRI造影剂,用于使用靶向磁性纳米粒子对HER2 / neu受体进行分子成像

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In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 ± 2.5 and 41 ± 15 nm (size range: 15–87 nm), respectively. The molar antibodyanoparticle ratio was 3.1–3.5. TMNs were non-toxic to the cells below the 30 μg (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.
机译:在这项研究中,制备曲妥珠单抗修饰的磁性纳米粒子(TMNs)作为一种新的造影剂,用于通过磁共振成像(MRI)检测HER2(人类表皮生长因子受体2)表达肿瘤。基于氧化铁纳米颗粒核和曲妥珠单抗修饰的右旋糖酐涂层制备TMN。通过透射电子显微镜和动态光散射确定TMNs的核和流体力学尺寸。研究了TMNs的稳定性和细胞毒性。通过MRI和铁摄取测定,在乳腺癌细胞系(SKBr3和MCF7细胞)和荷瘤小鼠中评估了TMNs检测HER2的能力。粒子的核心和流体力学尺寸分别为9±2.5 nm和41±15 nm(尺寸范围:15–87 nm)。抗体/纳米颗粒的摩尔比为3.1-3.5。浓度低于30μg(Fe)/ mL的TMN对细胞无毒,在PBS缓冲液中长达8周的稳定性良好。 TMNs可以通过MRI观察到明显的对比度来检测细胞表面的HER2癌基因。对荷瘤小鼠的体内研究表明,TMN作为MRI的HER2特异性造影剂具有良好的诊断能力。已证明TMN能够选择性地积聚在肿瘤细胞中,并且在MRI T2图像中具有适当的信号增强作用。因此,该复合物可以被认为是用于检测人中HER2表达肿瘤的MRI造影剂,以作进一步研究。

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