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An innovative peptide with high affinity to GPC3 for hepatocellular carcinoma diagnosis

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Abstract

Glypican-3 (GPC3) is a key biomarker for early diagnosis of human hepatocellular carcinoma (HCC) due to its overexpression in most HCC tumor tissues. Recently, peptides with high affinity to GPC3 have attracted more attention because of their high biocompatibility, non-immunogenicity, fast clearing and easy modification. Herein, we have designed an innovative GPC3 targeting peptide (sequence: DYEMHLWWGTEL, denoted as IPA) by using structure-based virtual simulation. The higher binding abilities of IPA over the reported peptide (YP) were displayed on different cell lines, showing a positive correlation with GPC3 expressions, which were further verified by the GPC3 protein binding assay. The GPC3 targeting specificity of IPA was proved by peptide blocking and siRNA experiment. The localized anchor of peptide IPA on the cell membranes of HepG2 and Huh-7 with GPC3 overexpression confirmed the GPC3 binding capacity. By connecting a near-infrared dye MPA, the in vivo identification ability of IPA to GPC3 was also demonstrated on GPC3-positive (HepG2) and GPC3-negative (U87) xenograft-bearing mice. These results indicated that the designed IPA presented desirable GPC3 targeting ability, showing promising prospects in detecting the expression of GPC3 for HCC targeting imaging.

Graphical abstract: An innovative peptide with high affinity to GPC3 for hepatocellular carcinoma diagnosis

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Publication details

The article was received on 22 Aug 2018, accepted on 17 Oct 2018 and first published on 25 Oct 2018


Article type: Paper
DOI: 10.1039/C8BM01016A
Citation: Biomater. Sci., 2019, Advance Article
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    An innovative peptide with high affinity to GPC3 for hepatocellular carcinoma diagnosis

    Q. Zhang, Z. Han, J. Tao, M. Zhao, W. Zhang, P. Li, L. Tang and Y. Gu, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C8BM01016A

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