应用T1加权超微小氧化铁纳米颗粒进行早期肝癌靶向磁共振成像的体内外研究

doi:10.24920/003643

摘要/Abstract

摘要： 目的制备精氨酰甘氨酸天冬氨酸肽（RGD）修饰的超小型超顺磁性氧化铁（Fe₃O₄）纳米粒（NPs）,用于肝细胞癌（HCC）细胞的靶向磁共振（MR）成像,并通过体外和体内实验验证其作为T1阳性磁共振成像对比剂的应用价值。方法将柠檬酸钠稳定的羧化Fe₃O₄ NPs与聚乙二醇（PEG）连接的RGD纳米粒子（NPs）偶联,形成靶向造影剂Fe₃O₄-PEG-RGD。通过HepG2细胞摄取和细胞MR成像,研究Fe3O4-PEG-RGD与RGD受体结合的特异性,并通过对裸鼠皮下HepG2肿瘤的体内MR成像,研究Fe₃O₄-PEG-RGD与RGD受体结合的特异性。结果合成的Fe₃O₄-PEG-RGD纳米颗粒具有良好的生物相容性和超高的r1弛豫率（1.37 mM ^-1S ^-1）,Fe₃O₄-PEG-RGD纳米颗粒的形貌均为球形,平均直径约2.7 nm。体外细胞摄取和细胞磁共振成像证实了其对HepG2细胞的靶向作用。同时,Fe₃O₄-PEG-RGD对小鼠肿瘤MR信号的增强作用明显高于非靶向Fe₃O₄-RGD。结果 Fe₃O₄-PEG-RGD颗粒在肝细胞癌靶向MR成像中作为T1阳性造影剂具有潜在的应用价值。

关键词: 肝细胞癌, 分子影像, 磁共振

Abstract: Objective The purpose of this study was to produce an arginylglycylaspartic acid (RGD) peptide-modified ultra-small superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) for targeted magnetic resonance (MR) imaging of hepatocellular carcinoma (HCC) cells and verify its utility as a T1 positive MRI imaging contrast agent in vitroand in vivo.Methods The carboxylated Fe₃O₄ NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD nanoparticles to form a novel target contrast agent Fe₃O₄-PEG-RGD NPs. The specificity of Fe₃O₄-PEG-RGD to bind RGD receptor was investigated in vitro by HepG2 cellular uptake and cell MR imaging, and in vivo by MR imaging of subcutaneous HepG2 tumors of nude mice.Results The formed Fe₃O₄-PEG-RGD NPs displayed good biocompatibility, and the ultrahigh r1 relaxivity was 1.37 mM ^-1S ^-1. The synthesized Fe₃O₄-PEG-RGD NPs were demonstrated spherical-like with an approximate diameter of 2.7 nm in similar size. The targeting effect to HepG2 cells was confirmed by in vitro cellular uptake and cell MR imaging. The in vivo MR imaging of nude mice demonstrated that the MR signal intensity enhancement of HepG2 tumor in Fe₃O₄-PEG-RGD NPs treated mice was significantly higher than in mice treated with non-targeted Fe₃O₄-mPEG NPs at the same post-administration time point. Conclusion The results indicate that the Fe₃O₄-PEG-RGD particles have potential utility as T1 positive contrast agent in targeted MR imaging.

Key words: hepatocellular carcinoma, molecular imaging, magnetic resonance imaging

基金资助: 上海交通大学“医工交叉研究基金”(YG2017QN25)

Xu Yanhong,Yang Jia,Meng Jie,Wang Han. Targeted MR Imaging Adopting T1-Weighted Ultra-Small Iron Oxide Nanoparticles for Early Hepatocellular Carcinoma: An in vitro and in vivo Study[J].Chinese Medical Sciences Journal, 2020, 35(2): 142-150.

图/表 7

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