Ultrahigh SERS activity of the TiO2@Ag nanostructure leveraged for accurately detecting CTCs in peripheral blood.
Ultrahigh SERS activity of the TiO2@Ag nanostructure leveraged for accurately detecting CTCs in peripheral blood.
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DOI：
10.1039/d1bm01821c
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发表时间：
2022-03
影响因子：
6.6
通讯作者：
Yanping Xu;Dinghu Zhang;Jie Lin;Xiaoxia Wu;Xiawei Xu;O. Akakuru;Hao Zhang;Zhewei Zhang;Yujiao Xie;Aiguo Wu;G. Shao
中科院分区：
文献类型：
--
作者：
Yanping Xu;Dinghu Zhang;Jie Lin;Xiaoxia Wu;Xiawei Xu;O. Akakuru;Hao Zhang;Zhewei Zhang;Yujiao Xie;Aiguo Wu;G. Shao
循环肿瘤细胞（Circulating tumor cells，CTC）是肿瘤的重要标志物，常从肿瘤的原发灶和转移灶脱落，易引起肿瘤患者的远处转移。准确有效地检测外周血样本中的CTC对于肿瘤的早期诊断、疗效评价和术后病情监测具有重要意义。本文以TiO2@Ag纳米结构为Sers基底，罗丹明6 G（R6 G）为拉曼信号分子，还原牛血清蛋白（rBSA）为保护剂，叶酸（FA）为靶分子，对癌细胞进行特异性识别。成功制备了TiO2@Ag基Sers生物探针，该探针具有灵敏度高、特异性好、毒性低、准确度高等特点。表面等离子体共振和光诱导电荷转移机制协同作用使TiO2@Ag纳米结构具有显著的Sers活性。吸附在TiO2@Ag基底上的罗丹明6 G（R6 G）分子的检测限为5 × 10-14 M，相应的Sers增强因子可达7.61 × 107。所设计的TiO 2 @ Ag-R6 G-rBSA-FA Sers生物探针可有效地用于检测兔血液中的多种癌细胞，对靶癌细胞的检测限（LOD）为1个细胞/mL。值得注意的是，通过基于TiO2@Ag的Sers生物探针成功识别了6名临床肝癌患者外周血中的CTC。基于TiO 2 @ Ag-R6 G-rBSA-FA Sers生物探针准确识别外周血中的CTC也通过原位免疫荧光染色实验仔细验证，这直接支持Sers策略的CTC检测准确性。这些结果表明TiO2@Ag基Sers生物探针在肿瘤的早期筛查和诊断方面具有很大的应用潜力。
Circulating tumor cells (CTCs) usually shed from primary and metastatic tumors serve as an important tumor marker, and easily cause fatal distant metastasis in cancer patients. Accurately and effectively detecting CTCs in a peripheral blood sample is of great significance in early tumor diagnosis, efficacy evaluation, and postoperative condition monitoring. In this work, a TiO2@Ag nanostructure is structured as a SERS substrate, rhodamine 6G (R6G) is used as a Raman signal molecule, the reduced bovine serum protein (rBSA) acts as a protective agent, and folic acid (FA) acts as a target molecule to specifically recognize cancer cells. A TiO2@Ag-based SERS bioprobe is successfully prepared with the feature of ultrahigh sensitivity, good specificity, low toxicity, and high accuracy in CTC detection. The remarkable SERS activity of the TiO2@Ag nanostructure is synergistically contributed by surface plasmon resonance and photon-induced charge transfer mechanism. The limit of detection for rhodamine 6G (R6G) molecules adsorbed on the TiO2@Ag SERS substrate is 5 × 10-14 M, and the corresponding SERS enhancement factor can reach 7.61 × 107. The designed TiO2@Ag-R6G-rBSA-FA SERS bioprobe is effectively utilized in detecting various cancer cells in rabbit blood, and the limit of detection (LOD) for the target cancer cell is 1 cell per mL. Notably, CTCs in peripheral blood of six clinical liver cancer patients are successfully recognized via the TiO2@Ag-based SERS bioprobe. Accurately recognizing CTCs in peripheral blood based on the TiO2@Ag-R6G-rBSA-FA SERS bioprobe is also carefully verified by in situ immunofluorescence staining experiments, which directly supports the CTC detection accuracy of the SERS strategy. These results demonstrate that the TiO2@Ag-based SERS bioprobe has great application potential in early screening and diagnosis of tumors.