Chinese Medical Sciences Journal ›› 2020, Vol. 35 ›› Issue (2): 142-150.doi: 10.24920/003643

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  1. 上海交通大学附属第一人民医院 放射科,上海 200080,中国
  • 收稿日期:2019-07-26 接受日期:2019-12-10 出版日期:2020-06-30 发布日期:2020-06-09
  • 通讯作者: 王悍

Targeted MR Imaging Adopting T1-Weighted Ultra-Small Iron Oxide Nanoparticles for Early Hepatocellular Carcinoma: An in vitro and in vivo Study

Xu Yanhong,Yang Jia,Meng Jie,Wang Han()   

  1. Department of Radiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China
  • Received:2019-07-26 Accepted:2019-12-10 Published:2020-06-30 Online:2020-06-09
  • Contact: Wang Han

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)

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