Open Access<strong>Targeted MR Imaging Adopting T1-weighted Ultra-Small Iron Oxide Nanoparticles for Early Hepatocellular Carcinoma：An in vitro and in vivo Study</strong>
Author(s) -
Yan Hong Xu,
Jia Yang,
Jie Meng,
Han Wang
Publication year - 2020
Publication title -
chinese medical sciences journal/chinese medical sciences journal
Language(s) - English
Resource type - Journals
ISSN - 1001-9294
DOI - 10.24920/003643
Subject(s) - in vivo , in vitro , medicine , peg ratio , polyethylene glycol , magnetic resonance imaging , hepatocellular carcinoma , cancer research , mri contrast agent , imaging agent , biocompatibility , cell , biophysics , materials science , chemistry , biochemistry , radiology , microbiology and biotechnology , biology , finance , metallurgy , economics
Objective The purpose of this study was to produce an arginylglycylaspartic acid (RGD) peptide-modified ultra-small superparamagnetic iron oxide (Fe 3 O 4 ) 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 vitro and in vivo .Methods The carboxylated Fe 3 O 4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD nanoparticles to form a novel target contrast agent Fe 3 O 4 -PEG-RGD NPs. The specificity of Fe 3 O 4 -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 Fe 3 O 4 -PEG-RGD NPs displayed good biocompatibility, and the ultrahigh r1 relaxivity was 1.37 mM -1 S -1 . The synthesized Fe 3 O 4 -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 Fe 3 O 4 -PEG-RGD NPs treated mice was significantly higher than in mice treated with non-targeted Fe 3 O 4 -mPEG NPs at the same post-administration time point. Conclusion The results indicate that the Fe 3 O 4 -PEG-RGD particles have potential utility as T1 positive contrast agent in targeted MR imaging.