Facile Synthesis of Lactobionic Acid-Targeted Iron Oxide Nanoparticles with Ultrahigh Relaxivity for Targeted MR Imaging of an Orthotopic Model of Human Hepatocellular Carcinoma

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• 作者：Yong Hu ; Ruizhi Wang ; Jingchao Li ; Ling Ding ; Xiaolin Wang ; Xiangyang Shi and Mingwu Shen
• 刊名：Particle & Particle Systems Characterization
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：34
• 期：1
• 全文大小：2177K
• ISSN：1521-4117

文摘

Development of multifunctional nanoprobes for tumor diagnosis is extremely important in the field of molecular imaging. In this study, the facile synthesis of lactobionic acid (LA)-targeted superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) with ultrahigh relaxivity for targeted magnetic resonance (MR) imaging of an orthotopic hepatocellular carcinoma (HCC) is reported. Polyethyleneimine (PEI)-stabilized Fe₃O₄ NPs prepared via a mild reduction route are sequentially coupled with fluorescein isothiocyanate and polyethylene glycol-LA (LA-PEG-COOH) segment, followed by acetylation of the remaining PEI surface amines. The formed LA-targeted Fe₃O₄ NPs are thoroughly characterized. It is shown that the developed multifunctional LA-targeted Fe₃O₄ NPs are colloidally stable and water-dispersible, display an ultrahigh r ₂ relaxivity (579.89 × 10⁻³ m ⁻¹ s⁻¹) and excellent hemocompatibility and cytocompatibility in the given concentration range, and can target HepG2 cells overexpressing asialoglycoprotein receptors as confirmed by in vitro cellular uptake assay, flow cytometry, and confocal microscopy. Most strikingly, the developed multifunctional LA-targeted Fe₃O₄ NPs can be used as a nanoprobe for targeted MR imaging of HepG2 cells in vitro and an orthotopic tumor model of HCC in vivo. With the ultrahigh r ₂ relaxivity and the versatile PEI amine-mediated conjugation chemistry, a range of different Fe₃O₄ NP-based nanoprobes may be developed for theranostics of different types of cancer.