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

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 aTl positive MRI imaging contrast agent in vitro and 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 rl relaxivity was 1.37 mM“S[The synthesized Fe3O4-PEG・RGD NPs were demonstrated sphericaLlike 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 asTl positive contrast agent in targeted MR imaging.