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MnO2-graphene oxide hybrid nanomaterial with oxidase-like activity for ultrasensitive colorimetric detection of cancer cells

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Abstract

Robust and sensitive cell-based enzyme-linked immunosorbent assay (CELISA) is of great significance in the diagnosis and screening of cancer. However, the method is limited by the high rate of negative results attributed to the instability of horseradish peroxidase (HRP), H2O2, and antibody. Here, we construct a folic acid–functionalized in situ-grown MnO2 nanosheet/graphene oxide hybrid (FA-MnO2/GO) with oxidase-like activity instead of the anti-folate receptor antibody in traditional CELISA to resist the possible negative interference arising from unstable HRP, H2O2, and antibodies for more robust colorimetric detection of cancer cells. The functionalization of FA enables the selective binding between hybrid and cancer cells through the over-expressed folate receptor, and then the binding events are converted into quantitative colorimetric signals though the oxidation of the chromogenic substrate TMB catalyzed by MnO2, allowing the detection of cancer cells with colorimetric method. Moreover, the construction of MnO2/GO hybrid can synergistically enhance the oxidase-like activity of MnO2 and promote its dispersion in water, further ensuring the accuracy and sensitivity of the detection. A detection limit of 20 cancer cells is obtained by a plate reader, which is lower than those obtained by most reported CELISA methods for cancer cell detection, and as few as 75 cancer cells can be identified by the naked eye. This study not only provides a multifunctional sensing platform for robust and sensitive cancer cell detection, but also offers a promising oxidase-like mimic in the field of bioanalysis.

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Funding

This work is financially supported by the National Natural Science Foundation of China (21922402, 21874017, and 21727811), Liaoning Provincial Program for Promoting Talents (XLYC1807005 and XLYC1802016), and the Fundamental Research Funds for the Central Universities (N2005027).

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Author notes

  1. Meng-Xian Liu and He Zhang contributed equally to this work.

Authors and Affiliations

  1. Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang, 110819, Liaoning, China

    Meng-Xian Liu, He Zhang, Yong-Liang Yu & Jian-Hua Wang

  2. College of Life and Health Sciences, Northeastern University, Shenyang, 110169, Liaoning, China

    Shuai Chen

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  1. Meng-Xian Liu
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  2. He Zhang
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Contributions

Meng-Xian Liu and He Zhang: Literature research, scheme design, data collection and processing, and original draft writing. Shuai Chen, Yong-Liang Yu, and Jian-Hua Wang: Scheme design, supervision, original draft writing, reviewing, and editing. All individuals who made contributions to this study are included as authors in this paper.

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Correspondence to Shuai Chen or Yong-Liang Yu.

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Liu, MX., Zhang, H., Chen, S. et al. MnO2-graphene oxide hybrid nanomaterial with oxidase-like activity for ultrasensitive colorimetric detection of cancer cells. Anal Bioanal Chem 413, 4451–4458 (2021). https://doi.org/10.1007/s00216-021-03399-0

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