Kai Fan1,2, Chengying Lu1, Gaofeng Shu1,3, Xiu-Ling Lv1, Enqi Qiao1,2, Nannan Zhang1, Minjiang Chen1,3, Jingjing Song1, Fazong Wu1, Zhongwei Zhao1, Xiaoling Xu3, Min Xu1, Chunmiao Chen1, Weibin Yang1, Jihong Sun2, Yongzhong Du4, Jiansong Ji5. 1. Department of Radiology, Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, School of Medicine, Lishui Hospital of Zhejiang University, Lishui, 323000, Zhejiang, China. 2. Department of Radiology, Sir Run Shaw Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China. 3. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. 4. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China. duyongzhong@zju.edu.cn. 5. Department of Radiology, Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, School of Medicine, Lishui Hospital of Zhejiang University, Lishui, 323000, Zhejiang, China. jijiansong@zju.edu.cn.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC. RESULTS: Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast. CONCLUSIONS: The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.
BACKGROUND:Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC. RESULTS: Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast. CONCLUSIONS: The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.
Entities:
Keywords:
Ferritin gene; Hepatocellular carcinoma; Magnetic resonance imaging; Polydopamine; Superparamagnetic iron oxide
Authors: Nam C Yu; Vinika Chaudhari; Steven S Raman; Charles Lassman; Myron J Tong; Ronald W Busuttil; David S K Lu Journal: Clin Gastroenterol Hepatol Date: 2010-10-01 Impact factor: 11.382
Authors: Neus Feliu; Dominic Docter; Markus Heine; Pablo Del Pino; Sumaira Ashraf; Jelena Kolosnjaj-Tabi; Paolo Macchiarini; Peter Nielsen; Damien Alloyeau; Florence Gazeau; Roland H Stauber; Wolfgang J Parak Journal: Chem Soc Rev Date: 2016-05-03 Impact factor: 54.564
Authors: Claudia Allemani; Hannah K Weir; Helena Carreira; Rhea Harewood; Devon Spika; Xiao-Si Wang; Finian Bannon; Jane V Ahn; Christopher J Johnson; Audrey Bonaventure; Rafael Marcos-Gragera; Charles Stiller; Gulnar Azevedo e Silva; Wan-Qing Chen; Olufemi J Ogunbiyi; Bernard Rachet; Matthew J Soeberg; Hui You; Tomohiro Matsuda; Magdalena Bielska-Lasota; Hans Storm; Thomas C Tucker; Michel P Coleman Journal: Lancet Date: 2014-11-26 Impact factor: 79.321
Authors: Kevin J Landmark; Stassi Dimaggio; Jesse Ward; Christopher Kelly; Stefan Vogt; Seungpyo Hong; Alina Kotlyar; Andrzej Myc; Thommey P Thomas; James E Penner-Hahn; James R Baker; Mark M Banaszak Holl; Bradford G Orr Journal: ACS Nano Date: 2008-04 Impact factor: 15.881