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Hyaluronic acid-grafted three-dimensional MWCNT array as biosensing interface for chronocoulometric detection and fluorometric imaging of CD44-overexpressing cancer cells

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Abstract

A sandwich-type electrochemical cytosensor is described for quantitative determination of CD44-overexpressing HeLa cells. Hyaluronic acid (HA) acts as a targeting molecule that was in-situ incorporated into the sensor based on the use of an indium tin oxide (ITO) electrode modified with multi-walled carbon nanotubes (MWCNTs). The 3D-MWCNT structure is shown to strongly improve the electronic properties and surface chemical reactivities. The HA-modified sensor exhibits a highly sensitive response to HeLa cells. A sandwiched hybridization protocol was then established using BIO [an N-butyl-4-(6′-aminohexyl)amino-1,8-naphthalimide probe modified with HA] as the tracing labels of the fluorescent probes for targeting CD44-positive tumor cells. The signal amplification was thereby maximized and measured by chronocoulometry. The binding of CD44-positive HeLa cells to the HA modified sensing layer causes a decrease in chronocoulometric response. The signal decreases linearly in the 2.1 × 102 to 2.1 × 107 HeLa cells·mL−1 concentration range with a detection limit of 70 cells·mL−1. Such a sandwich-type assay may be tailored as a sensitive candidate for detecting low levels of tumor cells.

Schematic of a sandwich cytosensor based on hyaluronic acid-grafted 3D-MWCNT as biosensing interface and BIO as fluorescent probe. This biosensor possessed excellent electrochemical activity, high sensitivity and selectivity, providing a dynamical tracking and detecting platform for CD44-positive tumor cells.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81472001, 21373138 and 31400851), the Minjiang Scholars Program of Fujian Province, the Tongjiang Scholars Program of Quanzhou City and the Fourth Health Education Joint Development Project of Fujian Province (WKJ-2016-2-36).

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  1. Minghuan Liu and Yanan Xu contributed equally to this work.

Authors and Affiliations

  1. College of Chemical Engineering and Materials Science, Quanzhou Normal University, Quanzhou, 362000, Fujian Province, China

    Minghuan Liu, Xiaoyan Zhang & Da-Peng Yang

  2. The Education Ministry Key Laboratory of Resource Chemistry Shanghai Key Laboratory of Rare Earth Functional Materials and Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Department of Chemistry, Shanghai Normal University, Shanghai, 200234, China

    Yanan Xu, Chusen Huang, Ti Jia & Nengqin Jia

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  1. Minghuan Liu
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  2. Yanan Xu
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Correspondence to Nengqin Jia.

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Liu, M., Xu, Y., Huang, C. et al. Hyaluronic acid-grafted three-dimensional MWCNT array as biosensing interface for chronocoulometric detection and fluorometric imaging of CD44-overexpressing cancer cells. Microchim Acta 185, 338 (2018). https://doi.org/10.1007/s00604-018-2861-z

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