Theranostics 2018; 8(12):3268-3274. doi:10.7150/thno.24711 This issue

Research Paper

Glypican-3-targeted precision diagnosis of hepatocellular carcinoma on clinical sections with a supramolecular 2D imaging probe

Hai-Hao Han1*, Yu-Jiao Qiu1*, Yuan-Yuan Shi2*, Wen Wen2, Xiao-Peng He1✉, Li-Wei Dong2✉, Ye-Xiong Tan2✉, Yi-Tao Long1, He Tian1, Hong-Yang Wang2 ✉

1. Key Laboratory for Advanced Materials & Feringa Nobel Prize Scientist Joint Research Center, East China University of Science and Technology (ECUST), 130 Meilong Rd., Shanghai 200237, PR China
2. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, the Second Military Medical University, Shanghai 200433, PR China
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Han HH, Qiu YJ, Shi YY, Wen W, He XP, Dong LW, Tan YX, Long YT, Tian H, Wang HY. Glypican-3-targeted precision diagnosis of hepatocellular carcinoma on clinical sections with a supramolecular 2D imaging probe. Theranostics 2018; 8(12):3268-3274. doi:10.7150/thno.24711. Available from

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Graphic abstract

The ability of chemical tools to effectively detect malignancy in frozen sections removed from patients during surgery is important for the timely determination of the subsequent surgical program. However, current clinical methods for tissue imaging rely on dye-based staining or antibody-based techniques, which are sluggish and complicated.

Methods: Here, we have developed a 2D material-based supramolecular imaging probe for the simple, rapid yet precise diagnosis of hepatocellular carcinoma (HCC). The 2D probe is constructed through supramolecular self-assembly between a water soluble, fluorescent peptide ligand that selectively targets glypican-3 (GPC-3, a specific cell-surface biomarker for HCC) and 2D molybdenum disulfide that acts as a fluorescence quencher as well as imaging enhancer.

Results: We show that the 2D imaging probe developed with minimal background fluorescence can sensitively and selectively image cells overexpressing GPC-3 over a range of control cells expressing other membrane proteins. Importantly, we demonstrate that the 2D probe is capable of rapidly (signal became readable within 1 min) imaging HCC tissues over para-carcinoma regions in frozen sections derived from HCC patients; the results are in accordance with those obtained using traditional clinical staining methods.

Conclusion: Compared to conventional staining methods, which are laborious (e.g., over 30 min is needed for antibody-based immunosorbent assays) and complex (e.g., diagnosis is based on discrimination of the nucleus morphology of cancer cells from that of normal cells), our probe, with its simplicity and quickness, might become a promising candidate for tumor-section staining as well as fluorescence imaging-guided surgery.

Keywords: hepatocellular carcinoma, glypican-3, 2D material, frozen section, diagnostics