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A GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma

Authors Zhao M, Liu Z, Dong L, Zhou H, Yang S, Wu W, Lin J

Received 15 March 2018

Accepted for publication 25 May 2018

Published 1 August 2018 Volume 2018:13 Pages 4433—4443


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun

Menglong Zhao,1 Zhuang Liu,2,3 Lili Dong,4,5 Hongxin Zhou,4,5 Shuohui Yang,6 Weizhong Wu,4,5 Jiang Lin1

1Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 2Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 4Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People’s Republic of China; 6Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China

Purpose: To construct and test a hepatocellular carcinoma (HCC)-targeted magnetic resonance probe based on a glypican-3 (GPC3)-specific aptamer (AP613-1) with ultrasmall superparamagnetic iron oxide (USPIO).
Methods: Oleic acid-coated USPIO nanoparticles were modified with amino polyethylene glycol on the surface. Amino groups of the USPIO nanoparticles were reacted with the carboxyl group of 5' carboxyl-modified AP613-1, forming an aptamer-mediated USPIO (Apt-USPIO) probe. The material characterization of this probe including transmission electron microscopy (TEM), zeta potential, dynamic laser scattering, and magnetic behavior was carried out. The targeting efficiency and magnetic resonance imaging (MRI) performance of Apt-USPIO were evaluated both in vitro and in vivo with USPIO alone as a control. The cytotoxicity and biocompatibility of Apt-USPIO and USPIO were analyzed by cell counting kit-8 tests in vitro and animal experiments in vivo.
Results: TEM imaging revealed that the Apt-USPIO nanoparticles were spherical in shape and well dispersed. Specific uptake of Apt-USPIO in Huh-7 cells could be observed using the Prussian blue staining test; however, no uptake of USPIO could be found. In vitro phantom T2-weighted MRI showed a significant decrease of the signal intensity in Apt-USPIO-incubated Huh-7 cells compared to USPIO-incubated Huh-7 cells. In vivo T2-weighted MRI showed significantly negative enhancement in the Huh-7 tumors enhanced with Apt-USPIO, whereas no enhancement was found with USPIO alone. Excellent biocompatibility of Apt-USPIO and USPIO was also demonstrated.
Conclusion: In this study, a molecular MRI probe which was highly specific to GPC3 on HCC was successfully prepared. Our results validated the targeted imaging effect of this Apt-USPIO probe in vivo for GPC3-expressing HCCs in xenograft mice.

Keywords: tumor-targeted imaging, carcinoma, hepatocellular, glypican-3, MRI, aptamer, ultrasmall superparamagnetic iron oxide

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