Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma

Jiaping Zhou,1 Qiaomei Zhou,1 Gaofeng Shu,2 Xiaojie Wang,1 Yuanfei Lu,1 Haiyan Chen,1 Tingting Hu,1 Jinsong Cai,1 Yongzhong Du,2 Risheng Yu1 1Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Institut...

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Autores principales:	Zhou J, Zhou Q, Shu G, Wang X, Lu Y, Chen H, Hu T, Cai J, Du Y, Yu R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	afp promoter magnetic resonance imaging transferrin targeted drug delivery hepatocellular carcinoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4b6d041f4040409e976a8e04c41a217d
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spelling	oai:doaj.org-article:4b6d041f4040409e976a8e04c41a217d2021-12-02T08:09:56ZDual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma1178-2013https://doaj.org/article/4b6d041f4040409e976a8e04c41a217d2020-09-01T00:00:00Zhttps://www.dovepress.com/dual-effect-of-magnetic-resonance-imaging-reporter-gene-in-diagnosis-a-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jiaping Zhou,1 Qiaomei Zhou,1 Gaofeng Shu,2 Xiaojie Wang,1 Yuanfei Lu,1 Haiyan Chen,1 Tingting Hu,1 Jinsong Cai,1 Yongzhong Du,2 Risheng Yu1 1Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of ChinaCorrespondence: Yongzhong DuInstitute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang Province, People’s Republic of ChinaTel +86 571 8820 8435Email duyongzhong@zju.edu.cnRisheng YuDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, People’s Republic of ChinaTel +86 571 8778 3925Email risheng-yu@zju.edu.cnPropose: The early diagnosis of hepatocellular carcinoma (HCC) with ferritin heavy chain (Fth) modified by alpha-fetoprotein (AFP) promoter has been studied. However, no study has focused on the considerable upregulation and specific targeting effects of transferrin receptors (TfR) caused by the transfection of plasmids encoded with the AFP promoter. Thus, the objective of our study was to investigate whether the transfection of Fth gene modified with AFP promoter (AFP@Fth) could be used for early diagnosis and enhanced treatment of HCC.Methods: The AFP@Fth plasmid was transfected into AFP positive cells. The expression of intracellular Ferritin was verified by Western blot, and the upregulation of TfR was confirmed by immunofluorescence and flow cytometry analysis. Cellular iron accumulation resulting in decreased imaging signals was examined by magnetic resonance imagining. Doxorubicin liposome modified with transferrin (Tf-LPD) was prepared to investigate the efficiency of the subsequent treatment after transfection. The enhanced drug distribution and effects were investigated both in vitro and in vivo.Results: Both Ferritin and TfR were overexpressed after transfection. The transfected cells showed higher intracellular iron accumulation and resulted in a lower MR T2-weighted imaging (T2WI) intensity, suggesting that the transfection of AFP@Fth could be a potential strategy for early diagnosis of liver cancer. The following treatment efficacy was revealed by Tf-LPD. As compared with un-transfected cells, transfected cells exhibited higher uptake of transferrin-modified liposomes (Tf-LP), which was due to the specific interaction between Tf and TfR overexpressed on the transfected cells. This is also the reason why Tf-LPD showed better in vitro and in vivo anticancer ability than doxorubicin loaded liposome (LPD). These results suggested that transfection of AFP@Fth could result in enhanced therapy of liver cancer.Conclusion: Transfection of AFP@Fth could be used for early diagnosis and for enhanced treatment of live cancers.Keywords: AFP promoter, magnetic resonance imaging, transferrin, targeted drug delivery, hepatocellular carcinomaZhou JZhou QShu GWang XLu YChen HHu TCai JDu YYu RDove Medical Pressarticleafp promotermagnetic resonance imagingtransferrintargeted drug deliveryhepatocellular carcinomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 7235-7249 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	afp promoter magnetic resonance imaging transferrin targeted drug delivery hepatocellular carcinoma Medicine (General) R5-920
spellingShingle	afp promoter magnetic resonance imaging transferrin targeted drug delivery hepatocellular carcinoma Medicine (General) R5-920 Zhou J Zhou Q Shu G Wang X Lu Y Chen H Hu T Cai J Du Y Yu R Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma
description	Jiaping Zhou,1 Qiaomei Zhou,1 Gaofeng Shu,2 Xiaojie Wang,1 Yuanfei Lu,1 Haiyan Chen,1 Tingting Hu,1 Jinsong Cai,1 Yongzhong Du,2 Risheng Yu1 1Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of ChinaCorrespondence: Yongzhong DuInstitute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang Province, People’s Republic of ChinaTel +86 571 8820 8435Email duyongzhong@zju.edu.cnRisheng YuDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, People’s Republic of ChinaTel +86 571 8778 3925Email risheng-yu@zju.edu.cnPropose: The early diagnosis of hepatocellular carcinoma (HCC) with ferritin heavy chain (Fth) modified by alpha-fetoprotein (AFP) promoter has been studied. However, no study has focused on the considerable upregulation and specific targeting effects of transferrin receptors (TfR) caused by the transfection of plasmids encoded with the AFP promoter. Thus, the objective of our study was to investigate whether the transfection of Fth gene modified with AFP promoter (AFP@Fth) could be used for early diagnosis and enhanced treatment of HCC.Methods: The AFP@Fth plasmid was transfected into AFP positive cells. The expression of intracellular Ferritin was verified by Western blot, and the upregulation of TfR was confirmed by immunofluorescence and flow cytometry analysis. Cellular iron accumulation resulting in decreased imaging signals was examined by magnetic resonance imagining. Doxorubicin liposome modified with transferrin (Tf-LPD) was prepared to investigate the efficiency of the subsequent treatment after transfection. The enhanced drug distribution and effects were investigated both in vitro and in vivo.Results: Both Ferritin and TfR were overexpressed after transfection. The transfected cells showed higher intracellular iron accumulation and resulted in a lower MR T2-weighted imaging (T2WI) intensity, suggesting that the transfection of AFP@Fth could be a potential strategy for early diagnosis of liver cancer. The following treatment efficacy was revealed by Tf-LPD. As compared with un-transfected cells, transfected cells exhibited higher uptake of transferrin-modified liposomes (Tf-LP), which was due to the specific interaction between Tf and TfR overexpressed on the transfected cells. This is also the reason why Tf-LPD showed better in vitro and in vivo anticancer ability than doxorubicin loaded liposome (LPD). These results suggested that transfection of AFP@Fth could result in enhanced therapy of liver cancer.Conclusion: Transfection of AFP@Fth could be used for early diagnosis and for enhanced treatment of live cancers.Keywords: AFP promoter, magnetic resonance imaging, transferrin, targeted drug delivery, hepatocellular carcinoma
format	article
author	Zhou J Zhou Q Shu G Wang X Lu Y Chen H Hu T Cai J Du Y Yu R
author_facet	Zhou J Zhou Q Shu G Wang X Lu Y Chen H Hu T Cai J Du Y Yu R
author_sort	Zhou J
title	Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma
title_short	Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma
title_full	Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma
title_fullStr	Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma
title_full_unstemmed	Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma
title_sort	dual-effect of magnetic resonance imaging reporter gene in diagnosis and treatment of hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/4b6d041f4040409e976a8e04c41a217d
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Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma

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