Near-Infrared Fluorescent Ag2S Nanodot-Based Signal Amplification

May 3, 2018 - Chem. , Article ASAP .... 3-Mercaptopropionic acid (MPA, 99%) was supplied from J&K Chemical Technology Co., Ltd. (Shanghai, China)...
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Near-infrared Fluorescent Ag2S Nanodot-based Signal Amplification for Efficient Detection of Circulating Tumor Cells Caiping Ding, Cuiling Zhang, Xueyang Yin, Xuanyu Cao, Meifang Cai, and Yuezhong Xian Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b00514 • Publication Date (Web): 03 May 2018 Downloaded from http://pubs.acs.org on May 3, 2018

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Analytical Chemistry

Caiping Ding, Cuiling Zhang*, Xueyang Yin, Xuanyu Cao, Meifang Cai, Yuezhong Xian* Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China. *E-mail: [email protected]; [email protected] ABSTRACT: The level of circulating tumor cells (CTCs) plays a critical role in tumor metastasis and personalized therapy, but it is challenging for highly efficient capture and detection of CTCs because of the extremely low concentration in peripheral blood. Herein, we report near-infrared fluorescent Ag2S nanodot-based signal amplification combing with immune-magnetic spheres (IMNs) for highly efficient magnetic capture and ultrasensitive fluorescence labeling of CTCs. The near-infrared fluorescent Ag2S nanoprobe has been successfully constructed through hybridization chain reactions using aptamer modified Ag2S nanodots, which can extremely improve the imaging sensitivity and reduce background signal of blood samples. Moreover, the anti-epithelial-celladhesion-molecule (EpCAM) antibody labeled magnetic nanospheres have been used for highly capture rare tumor cells in whole blood. The near-infrared nanoprobe with signal amplification and IMNs platform exhibits excellent performance in efficient capture and detection of CTCs, which shows great potential in cancer diagnostics and therapeutics.

Circulating tumor cells are viable cancer cells that are shed from original tumor into peripheral blood, which have been considered as prognostic biomarkers in tumor metastasis and cancer diagnostics.1 Therefore, the capture and detection of CTCs have benefited in the investigation of treatment progress monitoring and early diagnosis of metastatic relapse. 2-4 However, it is challenging due to the extremely rare counts in an extremely complex blood sample (only one CTC per 1 × 10 9 white blood cells).5 Thus, highly efficient isolation and analysis of CTCs from the whole blood are urgently needed. Numerous technologies and devices have been developed for the enrichment and detection of CTCs.6, 7 For example, microfluidic technologies for CTCs isolation have relied on the difference in the size between cancer cells and normal cells, which can increase the recovery of CTCs from cancer patients.8-13 However, these methods are achieved through microarrays and microfilters, limiting by complicated techniques and destructive release.14,15 Recently, some analytical methods with different signaling modes have been explored to detect CTCs, including electrochemistry,16-23 inductively coupled plasma-mass spectrometry,24,25 Raman imaging, 26 27-29 colorimetry, fluorescence30-39and so on. Especially, fluorescence-based assays have attracted much concerning due to the quick response, high sensitivity, non-destructivity and realtime monitoring. Many organic fluorescent dyes31-36 and fluorescent nanomaterials (CdSe/ZnS QDs37, CdTe/CdS QDs39 and AuNCs38) with visible light emission (