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

ObjectiveThe 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 vitro and in vivo.MethodsThe 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.ResultsThe 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.ConclusionThe results indicate that the Fe₃O₄-PEG-RGD particles have potential utility as T1 positive contrast agent in targeted MR imaging.