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揭示近红外氮杂硼二吡咯亚甲基(BODIPY)染料作为拉曼探针:基于表面增强拉曼散射(SERS)的人癌细胞选择性检测和成像。

Unveiling NIR Aza-Boron-Dipyrromethene (BODIPY) Dyes as Raman Probes: Surface-Enhanced Raman Scattering (SERS)-Guided Selective Detection and Imaging of Human Cancer Cells.

机构信息

Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram-, 695 019, Kerala, India.

Academy of Scientific and Innovative Research (AcSIR)-CSIR-NIIST, Thiruvananthapuram, India.

出版信息

Chemistry. 2017 Oct 12;23(57):14286-14291. doi: 10.1002/chem.201702626. Epub 2017 Sep 12.

Abstract

The development of new Raman reporters has attracted immense attention in diagnostic research based on surface enhanced Raman scattering (SERS) techniques, which is a well established method for ultrasensitive detection through molecular fingerprinting and imaging. Herein, for the first time, we report the unique and efficient Raman active features of the selected aza-BODIPY dyes 1-6. These distinctive attributes could be extended at the molecular level to allow detection through SERS upon adsorption onto nano-roughened gold surface. Among the newly revealed Raman reporters, the amino substituted derivative 4 showed high signal intensity at very low concentrations (ca. 0.4 μm for 4-Au). Interestingly, an efficient nanoprobe has been constructed by using gold nanoparticles as SERS substrate, and 4 as the Raman reporter (4-Au@PEG), which unexpectedly showed efficient recognition of three human cancer cells (lung: A549, cervical: HeLa, Fibrosarcoma: HT-1080) without any specific surface marker. We observed well reflected and resolved Raman mapping and characteristic signature peaks whereas, such recognition was not observed in normal fibroblast (3T3L1) cells. To confirm these findings, a SERS nanoprobe was conjugated with a specific tumour targeting marker, EGFR (Epidermal Growth Factor Receptor), a well known targeted agent for Human Fibrosarcoma (HT1080). This nanoprobe efficiently targeted the surface marker of HT1080 cells, threreby demonstrating its use as an ultrasensitive Raman probe for detection and targeted imaging, leaving normal cells unaffected.

摘要

新型拉曼报告分子的发展在基于表面增强拉曼散射(SERS)技术的诊断研究中引起了极大的关注,这是一种通过分子指纹图谱和成像进行超灵敏检测的成熟方法。在此,我们首次报道了所选择的氮杂-BODIPY 染料 1-6 的独特且高效的拉曼活性特征。这些独特的属性可以在分子水平上扩展,使其在吸附到纳米粗糙金表面后能够通过 SERS 进行检测。在新揭示的拉曼报告分子中,取代的氨基衍生物 4 在非常低的浓度(约 4-Au 的 0.4μm)下显示出高信号强度。有趣的是,通过使用金纳米粒子作为 SERS 基底和 4 作为拉曼报告分子(4-Au@PEG)构建了一种高效的纳米探针,它出人意料地对三种人类癌细胞(肺癌:A549、宫颈癌:HeLa、纤维肉瘤:HT-1080)表现出有效的识别能力,而无需任何特定的表面标记。我们观察到了良好反射和分辨的拉曼映射和特征峰,而在正常成纤维细胞(3T3L1)中则没有观察到这种识别。为了证实这些发现,将 SERS 纳米探针与一种特定的肿瘤靶向标记物 EGFR(表皮生长因子受体)缀合,EGFR 是一种众所周知的用于人类纤维肉瘤(HT1080)的靶向剂。这种纳米探针有效地靶向 HT1080 细胞的表面标记物,从而证明其可作为用于检测和靶向成像的超灵敏拉曼探针,而对正常细胞没有影响。

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