Glypican-3 (GPC3), the cellular membrane proteoglycan, has been established as a tumor biomarker for early diagnosis of hepatocellular carcinoma (HCC). GPC3 is highly expressed in more than 70% HCC tissues detected by antibody-based histopathological systems. Recently, aptamers, a short single-strand DNA or RNA generated from systematic evolution of ligands by exponential enrichment (SELEX), were reported as potential alternatives in tumor-targeted imaging and diagnosis. In this study, a total of 19 GPC3-bound aptamers were successfully screened by capillary electrophoresis (CE)-SELEX technology. After truncated, AP613-1 was confirmed to specifically target GPC3 with a dissociation constant (KD) of 59.85 nM. When modified with a phosphorothioate linkage, APS613-1 targeted GPC3 with a KD of 15.48 nM and could be used as a specific probe in living Huh7 and PLC/PRF/5 imaging, GPC3-positive cell lines, but not in L02 or A549, two GPC3-negative cell lines. More importantly, Alexa Fluor 750-conjugated APS613-1 could be used as a fluorescent probe to subcutaneous HCC imaging in xenograft nude mice. Our results indicated that modified AP613-1, especially APS613-1, was a potential agent in GPC3-positive tumor imaging for HCC early diagnosis.
Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-11436 |
Date | 07 December 2018 |
Creators | Dong, Lili, Zhou, Hongxin, Zhao, Menglong, Gao, Xinghui, Liu, Yang, Liu, Dongli, Guo, Wei, Hu, Hongwei, Xie, Qian, Fan, Jia, Lin, Jiang, Wu, Weizhong |
Publisher | Digital Commons @ East Tennessee State University |
Source Sets | East Tennessee State University |
Detected Language | English |
Type | text |
Format | application/pdf |
Source | ETSU Faculty Works |
Rights | http://creativecommons.org/licenses/by/4.0/ |
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