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Gd2O3-doped silica @ Au Nanoparticles for In Vitro Imaging Cancer Biomarkers Using Surface-Enhanced Raman scattering

机译:使用表面增强拉曼散射对Gd2O3掺杂的二氧化硅@ Au纳米粒子进行体外成像癌症生物标记物

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摘要

There has been an interest in developing multimodal approaches to combine the advantages of individual imaging modalities, as well as to compensate for respective weaknesses. We previously reported a composite nano-system composed of gadolinium-doped mesoporous silica nanoparticle and gold nanoparticle (Gd-Au NPs) as an efficient MRI contrast agent for in vivo cancer imaging. However, the MRI lacks sensitivity and is unsuitable for in vitro cancer detection. Thus, here we performed a study to use the Gd-Au NPs for detection and imaging of a widely recognized human cancer biomarker, epidermal growth factor receptor (EGFR), in individual human cancer cells with surface-enhanced Raman scattering (SERS). The Gd-Au NPs were sequentially conjugated with a monoclonal antibody recognizing EGFR and a Raman reporter molecule, 4-meraptobenzoic acid (MBA), to generate characteristic SERS signal at 1075 cm−1. By spatially mapping the SERS intensity at 1075 cm−1, cellular distribution of EGFR and relocalization on the plasma membrane were measured in situ. In addition, the EGFR expression level in three human cancer cell lines (S18, A431 and A549) was measured using this SERS probe, which was consistent with the comparable measurements using immunoblotting and immunofluorescence. Our SERS results show that functionalized Gd-Au NPs successfully targeted EGFR molecules in three human cancer cell lines and monitored changes in single cell EGFR distribution in situ, demonstrating its potential to study cell activity under physiological conditions. This SERS study, combined with our previous MRI study, suggests the Gd-Au nanocomposite is a promising candidate contrast agent for multimodal cancer imaging.
机译:人们对开发多模式方法以结合各个成像模式的优点以及弥补各自的弱点感兴趣。我们先前报道了由nano掺杂的介孔二氧化硅纳米粒子和金纳米粒子(Gd-Au NPs)组成的复合纳米系统,作为体内癌症成像的有效MRI造影剂。然而,MRI缺乏敏感性并且不适用于体外癌症检测。因此,在这里,我们进行了一项研究,利用Gd-Au NPs在具有表面增强拉曼散射(SERS)的单个人类癌细胞中检测和成像广泛认可的人类癌症生物标记物,表皮生长因子受体(EGFR)。依次将Gd-Au NP与识别EGFR的单克隆抗体和拉曼报告分子4-巯基苯甲酸(MBA)偶联,以在1075 cm -1 处生成特征性SERS信号。通过在1075 cm -1 处空间映射SERS强度,就地测量EGFR的细胞分布和在质膜上的重新定位。此外,使用此SERS探针测量了三种人类癌细胞系(S18,A431和A549)中的EGFR表达水平,这与使用免疫印迹和免疫荧光法进行的可比较测量结果一致。我们的SERS结果表明,功能化的Gd-Au NP成功地靶向了三种人类癌细胞系中的EGFR分子,并监测了单细胞EGFR原位分布的变化,证明了其在生理条件下研究细胞活性的潜力。这项SERS研究与我们先前的MRI研究相结合,表明Gd-Au纳米复合材料是多模态癌症成像的有希望的候选造影剂。

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