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

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 Universi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhao M, Liu Z, Dong L, Zhou H, Yang S, Wu W, Lin J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Tumor-targeted imaging Carcinoma Hepatocellular Glypican-3 MRI Aptamer Ultrasmall superparamagnetic iron oxide Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0eb585685d54491ca9d1e23c5214ce58
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0eb585685d54491ca9d1e23c5214ce58
record_format	dspace
spelling	oai:doaj.org-article:0eb585685d54491ca9d1e23c5214ce582021-12-02T05:16:59ZA GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma1178-2013https://doaj.org/article/0eb585685d54491ca9d1e23c5214ce582018-08-01T00:00:00Zhttps://www.dovepress.com/a-gpc3-specific-aptamer-mediated-magnetic-resonance-probe-for-hepatoce-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Menglong 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 oxideZhao MLiu ZDong LZhou HYang SWu WLin JDove Medical PressarticleTumor-targeted imagingCarcinomaHepatocellularGlypican-3MRIAptamerUltrasmall superparamagnetic iron oxideMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4433-4443 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tumor-targeted imaging Carcinoma Hepatocellular Glypican-3 MRI Aptamer Ultrasmall superparamagnetic iron oxide Medicine (General) R5-920
spellingShingle	Tumor-targeted imaging Carcinoma Hepatocellular Glypican-3 MRI Aptamer Ultrasmall superparamagnetic iron oxide Medicine (General) R5-920 Zhao M Liu Z Dong L Zhou H Yang S Wu W Lin J A GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma
description	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
format	article
author	Zhao M Liu Z Dong L Zhou H Yang S Wu W Lin J
author_facet	Zhao M Liu Z Dong L Zhou H Yang S Wu W Lin J
author_sort	Zhao M
title	A GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma
title_short	A GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma
title_full	A GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma
title_fullStr	A GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma
title_full_unstemmed	A GPC3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma
title_sort	gpc3-specific aptamer-mediated magnetic resonance probe for hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/0eb585685d54491ca9d1e23c5214ce58
work_keys_str_mv	AT zhaom agpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT liuz agpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT dongl agpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT zhouh agpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT yangs agpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT wuw agpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT linj agpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT zhaom gpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT liuz gpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT dongl gpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT zhouh gpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT yangs gpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT wuw gpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma AT linj gpc3specificaptamermediatedmagneticresonanceprobeforhepatocellularcarcinoma
_version_	1718400454751158272

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

Ejemplares similares