Using PEGylated iron oxide nanoparticles with ultrahigh relaxivity for MR imaging of an orthotopic model of human hepatocellular carcinoma

  • Ruizhi Wang
  • Yong Hu
  • Yuchan Yang
  • Wei Xu
  • Mingrong Yao
  • Dongmei Gao
  • Yan Zhao
  • Songhua Zhan
  • Xiangyang Shi
  • Xiaolin Wang
Research Paper


Hepatocellular carcinoma (HCC) is the most common type of liver malignant tumor, which is often diagnosed in advanced stages, resulting in low survival rate. The sensitive diagnosis of early HCC presents a great interest. Herein, a novel superparamagnetic contrast agent composed of iron oxide nanoparticles is reported. Firstly, polyethyleneimine-coated iron oxide (Fe3O4@PEI) nanoparticles (NPs) were synthesized via a mild reduction route, followed by their modification of polyethylene glycol monomethyl ether (mPEG-COOH) via 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride coupling chemistry. After acetylation of the remaining PEI amines, the PEGylated Fe3O4 (Fe3O4@PEI.Ac-mPEG-COOH) NPs were successively characterized via different techniques. The Fe3O4@PEI.Ac-mPEG-COOH probes with an Fe3O4 NP size of 9 nm are water dispersible and cytocompatible within the given concentration range. The percentages of PEI and m-PEG-COOH on the particles surface are calculated to be 15.5 and 7.2%, respectively. Prior to the administration of Fe3O4@PEI.Ac-mPEG-COOH NPs of ultrahigh r 2 relaxivity (461.29 mM−1 s−1) via tail intravenous injection for MR imaging of HCC, the orthotopic model of HCC was established in the nude mice by surgical transplantation with HCCLM3 cells. The analysis of MR signal intensity (SI) in the orthotopic tumor model demonstrated that the developed Fe3O4@PEI.Ac-mPEG-COOH NPs were able to infiltrate into the tumor area through the enhanced permeability and retention (EPR) effect reaching the bottom at 2 h postinjection. The developed Fe3O4@PEI.Ac-mPEG-COOH NPs may be further applied for theranostics of different diseases through combing various therapeutic agents.


Polyethyleneimine Polyethylene glycol Iron oxide nanoparticles Orthotopic hepatocellular carcinoma MR imaging 



This research is financially supported by the National Natural Science Foundation of China (21273032, 81101150, 81341050, and 81371623), the Sino-German Center for Research Promotion (GZ899), the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, and the Fundamental Research Funds for the Central Universities (EG2015021).

Compliance with ethical standards

All animal experiments were carried out in accordance with protocols approved by the ethical committee of Zhongshan Hospital.

Competing fnancial interests

The authors declare no competing fnancial interests.


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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Shanghai Institute of Medical Imaging, Department of Interventional Radiology, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Department of Interventional RadiologyXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
  3. 3.College of Chemistry, Chemical Engineering and BiotechnologyDonghua UniversityShanghaiPeople’s Republic of China
  4. 4.Department of RadiologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiPeople’s Republic of China
  5. 5.Liver Cancer Institute, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China

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