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方酸染料的聚集诱导拉曼散射:通过 SERS 成像在宫颈癌前病变诊断中的应用。

Aggregation induced Raman scattering of squaraine dye: Implementation in diagnosis of cervical cancer dysplasia by SERS imaging.

机构信息

CSIR-National Institute for Interdisciplinary Science & Technology (NIIST), Chemical Science & Technology Division (CSTD), Organic Chemistry Section, Industrial Estate, Thiruvananthapuram 695019, Kerala, India.

Sree Chitra Tirunal Institute for Medical Sciences & Technology, FADDS, Biomedical Technology Wing, Poojappura, Thiruvananthapuram 695012, Kerala, India.

出版信息

Biosens Bioelectron. 2015 Aug 15;70:145-52. doi: 10.1016/j.bios.2015.03.029. Epub 2015 Mar 14.

DOI:10.1016/j.bios.2015.03.029
PMID:25801955
Abstract

The extent of squaraine dye aggregation that reflects on surface enhanced Raman signal scattering (SERS) intensity upon adsorption on nano-roughened gold surface has been investigated. Here we have synthesized a serious of six squaraine dyes consisting of two different electron donor moiety i.e. 1,1,2-trimethyl-1H-benzo[e]indole and 2-methylbenzo[d]thiazole which modulates the chemisorptions and hydrophobicity being designated as SQ1, SQ2, SQ3, SQ4, SQ5 and SQ6. Interestingly, SQ2 (mono lipoic acid appended), SQ5 and SQ6 (conjugated with hexyl and dodecyl side chain) squaraine derivatives having more tendency of aggregation in DMSO-water mixed solvent showed significant increase of Raman scattering in the fingerprint region when chemisorbed on spherical gold nanoparticles. Two sets of SERS nanotags were prepared with colloidal gold nanoparticle (Au-NPs size: 40 nm) by incorporating Raman reporters SQ2 and SQ5 followed by thiolated PEG encapsulation (SH-PEG, SH-PEG-COOH) denoted as AuNPs-SQ2-PEG and AuNPs-SQ5-PEG. Further conjugation of these nanotag with monoclonal antibodies specific to over expressed receptors, EGFR and p16/Ki-67 in cervical cancer cell, HeLa showed prominent SERS mapping intensity and selectivity towards cell surface and nucleus. The fast and accurate recognition obtained by antibody triggered SERS-nanotag has been compared with conventional time consuming immunocytochemistry technique which prompted us to extend further investigation using real patient cervical smear sample for a non-invasive, ultrafast and accurate diagnosis.

摘要

已经研究了吸附在纳米粗糙金表面上的方酸染料聚集程度对表面增强拉曼信号散射(SERS)强度的影响。在这里,我们合成了一系列由两个不同的电子供体部分组成的六种方酸染料,即 1,1,2-三甲基-1H-苯并[e]吲哚和 2-甲基苯并[d]噻唑,它们调节化学吸附和疏水性,被指定为 SQ1、SQ2、SQ3、SQ4、SQ5 和 SQ6。有趣的是,SQ2(单脂酰基 appended)、SQ5 和 SQ6(与己基和十二烷基侧链共轭)方酸衍生物在 DMSO-水混合溶剂中更倾向于聚集,当化学吸附在球形金纳米粒子上时,指纹区域的拉曼散射显著增加。两组 SERS 纳米标签是通过将拉曼报告器 SQ2 和 SQ5 掺入胶体金纳米粒子(Au-NPs 尺寸:40nm)并随后进行硫醇化 PEG 封装(SH-PEG、SH-PEG-COOH)来制备的,分别表示为 AuNPs-SQ2-PEG 和 AuNPs-SQ5-PEG。进一步将这些纳米标签与针对宫颈癌细胞 HeLa 中过表达受体 EGFR 和 p16/Ki-67 的单克隆抗体进行缀合,显示出对细胞表面和核的突出 SERS 映射强度和选择性。通过抗体触发 SERS-纳米标签获得的快速准确识别与传统费时的免疫细胞化学技术进行了比较,这促使我们进一步使用真实的患者宫颈涂片样本进行非侵入性、超快和准确的诊断。

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