Chemical Research in Chinese Universities ›› 2021, Vol. 37 ›› Issue (4): 919-924.doi: 10.1007/s40242-021-1159-6

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DNA Framework-based Topological Aptamer for Differentiating Subtypes of Hepatocellular Carcinoma Cells

YIN Fangfei1, CAO Nan2, XIANG Xuelin2, FENG Hao1, LI Fan1, LI Min1, XIA Qiang1, ZUO Xiaolei1,2   

  1. 1. Institute of Molecular Medicine, Department of Liver Surgery, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P. R. China;
    2. School of Chemistry and Chemical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, P. R. China
  • Received:2021-04-06 Revised:2021-04-22 Online:2021-08-01 Published:2021-05-13
  • Contact: LI Min E-mail:mlisinap@163.com
  • Supported by:
    This work was supported by the National Key Research and Development Program of China(No.2020YFA0909000), the National Natural Science Foundation of China(Nos.92059205, 22025404, 21904086, 21804091), and the Shanghai Pujiang Program, China(No.19PJ1407300).

Abstract: Hepatocellular carcinoma(HCC) remains a global health challenge with a growing incidence worldwide. The accurate identification of liver HCC cell subtypes plays crucial roles in precision medicine and prognosis. Nevertheless, simple and efficient methods for cell subtype discrimination still remain an issue to be studied. In this study, we construct topological probes by using a tetrahedral DNA framework(TDF) to topologically engineer the spatial orientations of the aptamers. The three vertexes of a TDF were algebraic topologically anchored with aptamers targeting epithelial cell adhesion molecule(EpCAM), which may express differently on different subtypes of HCC cells. Using the TDF-based topological aptamer(TDF-TA), we accomplish the differentiation of HCC cell subtypes, including high-metastatic, low-metastatic HCC and normal cells based on flow cytometry(FCM) and fluorescence microscope imaging. By replacing the fluorescent indicator modified on aptamers with photoacoustic dyes, we achieve the discrimination of different HCC cells using photoacoustic imaging technology, further demonstrating the feasibility of the TDF-based topological probe for HCC cell subtype discrimination. This TDF-based topolo-gical engineering strategy thus provides a flexible means for subtype cell discrimination, which may provide new ideas for achieving accurate diagnosis of HCC.

Key words: Topological aptamer, Tetrahedral DNA framework, Cell classification, Cell imaging