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

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• 作者：Ruizhi Wang ; Yong Hu ; Yuchan Yang ; Wei Xu ; Mingrong Yao…
• 关键词：Polyethyleneimine ; Polyethylene glycol ; Iron oxide nanoparticles ; Orthotopic hepatocellular carcinoma ; MR imaging
• 刊名：Journal of Nanoparticle Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：19
• 期：2
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Nanotechnology; Inorganic Chemistry; Characterization and Evaluation of Materials; Physical Chemistry; Optics, Lasers, Photonics, Optical Devices;
• 出版者：Springer Netherlands
• ISSN：1572-896X
• 卷排序：19

文摘

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 r₂ 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.