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Determination of VEGF165 using impedimetric aptasensor based on cyclohexanehexone-melem covalent-organic framework

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Abstract

A porous nanostructured covalent-organic framework (COF) has been prepared via condensation polymerization between the two building blocks of melem and hexaketocyclohexane octahydrate (represented as M-HO-COF). Basic characterizations revealed that the M-HO-COF network was composed of C=N and highly conjugated aromatic moieties, along with a high surface area, large pore size, remarkable electrochemical activity, and strong bioaffinity toward aptamer strands. Given that the vascular endothelial growth factor 165 (VEGF165)-targeted aptamer was stably anchored over M-HO-COF via weak intermolecular forces, the prepared M-HO-COF network exhibited great potential as a sensitive and selective platform for the impedimetric VEGF165 aptasensor. Consequently, the M-HO-COF-based aptasensor displayed an ultralow limit of detection of 0.18 fg mL−1 within a wide range of VEGF165 concentrations from 1 fg mL−1 to 10 ng mL−1. Considering its strong fluorescence performance, excellent biocompatibility, and small nanosheet-like structure, the obtained COF-based aptasensor showed a superior sensing performance and regeneration capability after 7 regeneration cycles for the detection of osteosarcoma cells (K7M2 cells), which overexpressed with VEGF165, with a low limit of detection of 49 cells mL−1. For real f human serum samples, the obtained COF-based aptasensor exhibits acceptable mean apparent recoveries of 97.41% with a relative standard deviation of 4.60%. Furthermore, the proposed bifunctional aptasensor for the detection VEGF165 and K7M2 cells exhibited good stability, appropriate selectivity toward other biomarkers or normal cells, acceptable reproducibility, and applicability.

Graphical abstract

A bifunctional sensing system was constructed for detecting osteosarcoma cells (K7M2 cells) and VEGF165 based on the a porous nanostructured covalent-organic framework (M-HO-COF) via condensation polymerization between melem and hexaketocyclohexane octahydrate. The M-HO-COF-based aptasensor displayed ultralow detection limit of 0.18 fg mL−1 toward VEGF165 and 49 cell mL−1 for K7M2 cells with high selectivity, acceptable reproducibility, and good stability.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 82071388, 81601082, 81771329), China Postdoctoral Science Foundation (2019 M660175), and Henan Distinguished Youth Science Fund Project (CN) (No. 202300410492).

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  1. Jiangnan Li and Yang Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, People’s Republic of China

    Jiangnan Li, Yang Liu, Geyi Zhang, Xiaoyu Huang & Nan Zhou

  2. School of Materials and Chemical Engineering, Zhengzhou University of Light Industry, No. 136, Science Avenue, Zhengzhou, 450001, People’s Republic of China

    Changbao Wang, Qiaojuan Jia & Zhihong Zhang

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  1. Jiangnan Li
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  2. Yang Liu
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Correspondence to Nan Zhou or Zhihong Zhang.

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Supplementary information

Experimental section; Chemical structure of M-OH-COF; Analysis of cell cytotoxicity for M-OH-COF; Electrochemical performances of M-OH-COF-based aptasensor; Optimization of experimental conditions for sensing VEGF165 and K7M2 cells; Determination of real sample using the proposed aptasensors.

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Li, J., Liu, Y., Wang, C. et al. Determination of VEGF165 using impedimetric aptasensor based on cyclohexanehexone-melem covalent-organic framework. Microchim Acta 188, 211 (2021). https://doi.org/10.1007/s00604-021-04843-9

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